IFM White Paper 21st Century Medicine
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21st
century
medicine:
A New Model for Medical
Education and Practice
David S. Jones, MD
Laurie Hofmann, MPH
Sheila Quinn
©2009 The Institute for Functional Medicine
4411 Pt Fosdick Dr NW, Ste 305
Gig Harbor, WA 98335
The Institute for Functional Medicine and IFM are marks owned by Jeffrey and Susan Bland,
used under exclusive license.
21st Century Medicine | i
21st
century
medicine:
A New Model for Medical
Education and Practice
Table of Contents
Page No.
Preface ........................................................................................... iii
Foreword ...................................................................................... vii
Executive Summary ...................................................................... xi
Chapter 1 Introduction .............................................................. 1
Chapter 2 The Changing Medical Environment ....................... 9
Chapter 3 Emerging Models .................................................... 23
Chapter 4 The Clinician’s Dilemma ........................................ 43
Chapter 5 Functional Medicine: A 21st Century Model
of Patient Care and Medical Education ................ 61
References .................................................................................... 80
About the Institute for Functional Medicine ............................... 88
Appendix Table of Contents ...................................................... A1
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21st
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medicine:
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Education and Practice
21st Century Medicine | iii
Preface
________________________________________
Beginning a Journey of Discovery
The document you are about to read emerged from a systematic process of
inquiry and intentionality about some of the most critical issues in health care
today. While there are many vital structural factors to be addressed elsewhere
(reimbursement practices, insurance coverage, electronic medical records, the
medical home concept), our attention and expertise are here focused on the
content and process of care. The path we followed to conceive of, research, and
write this white paper on 21st century medicine can be traced back to 2006, when
the Fountainhead Foundation approved a grant to The Institute for Functional
Medicine to establish and manage a scholarship program for medical schools and
residency programs to send selected faculty, students, and residents to learn about
functional medicine. Over a two-year period, 57 scholarships were awarded,
representing 27 medical schools and 6 residency programs. The impact and
opportunities that have grown out of this seed funding have been signicant,
immediate, and wide-ranging across academic medicine, clinical programs,
fellowships, and residency programs.
Our interviews, meetings, and follow-up discussions with scholarship recipients
and their colleagues underscored the fact that IFM needed to provide a rationale
and methodology for facilitating a more systematic and widespread introduction
of functional medicine into these diverse institutions and programs. It is very
arduous to modify both the process and content of medical education. There
must be a compelling reason and a clear path toward the goal. Our journey
therefore, involved documenting the urgent need for a major shift in medical
education, and then describing a model of care that can be adapted to the
teaching needs of medical (and other health professions) schools and residency
programs. In so doing, we provide both the justication for, and a description of,
the change that must occur to equip clinicians to adapt successfully to the health
care demands of the 21st century.
We looked rst at relevant major themes in health care today: the epidemic of
chronic disease; the evolution of evidence-based medicine; the poor performance
of the acute-care model in a chronic care environment; the emergence of new
paradigms such as systems biology, integrative medicine, and personalized care;
and the lack of consensus on how to address these issues in a systematic way.
21st century medicine:
A New Model for Medical Education and Practice
iv | 21st Century Medicine
This journey took us deep into the literature of costs vs. performance, science vs. art, research vs. clinical
practice, and the many ideas about how to consolidate the gains of the 20th century without losing
exibility or constraining the promise of new information and new models of care for the future.
With this background in place, we began to explore how all of this looks and feels to the individual
clinician who is immersed in the daily demands of clinical practice. This, of course, is where the rubber
meets the road. We found that not only have we failed to materially assist most primary care practitioners
in understanding how to make better use of evidence, or in translating new tools and ideas into their
clinical practice, but we have left clinical medicine poorly equipped to address two critical elements:
(1) managing the uncertainty that is inherent in clinical practice, and (2) creating a healing partnership
with their patients. We found that clinicians are no longer taught how to integrate the science and the
art of medicine—indeed, the art of medicine has all but disappeared as a subject of teaching. From
the evidence-based medicine perspective, all you really need to do is gather data, focus the data toward
securing the diagnosis, and then research the evidence about the best molecule (Rx) or procedure to treat
that diagnosis. Doctors trained in the EBM, acute-care model have become technicians. Converging
pressures have reinforced this model by forcing doctors to focus their ofce visits more and more narrowly,
and to deliver care in less and less time (often for less and less money).
If this model worked, we wouldn’t have had grounds for writing this paper. Unfortunately, the model has
failed spectacularly to help stem the rising tide of chronic disease. Fortunately, however, there is plenty of
evidence that this is not the only way forward. Physicians and other practitioners can be taught to shift
into a personalized, systems-medicine approach that is much better adapted to the complex demands
of chronic disease. They can learn to gather and analyze patient data differently. They can twist the
kaleidoscope and apply critical thinking to the use of evidence. And they can create healing partnerships
that allow both patients and practitioners to achieve insight and then to evaluate that insight in the light
of knowledge and experience.
Reintegrating the Science and Art of Medicine
There are always two deeply powered processes at work in any life-changing endeavor. Human beings
require both denotative and connotative information for mastery—that is, we need both data and
intuition, science and art. Brain scientists have made great progress in illuminating the deep creative
processes by which our “minds” make use of the “matter” of our brains.”1,2,3,4,5,6 Clinicians, particularly,
need to bring to the therapeutic encounter the unique qualities of both right- and left-brain function
that have been emerging from brain science research. In the last decade, wider use of functional imaging
technology has delivered a much clearer picture of coordinated brain function—why and how it occurs.
It is now possible to weave together the integrated functionality of the two sides of the brain in a way that
can inform our understanding about a comprehensive patient care model that respects and integrates both
the science and the art of medicine.
The Institute for Functional Medicine (IFM) has developed a model of comprehensive care and primary
prevention for complex, chronic illness that is grounded in both the science (the Functional Medicine Matrix
Model™) and the art (the healing partnership in the therapeutic encounter) of clinical medicine. We call
this model functional medicine, and we have taught it for many years. It is not a separate discipline or
specialty—it is an approach to clinical care that is both comprehensive and patient-centered. It can be
PreFAce
21st Century Medicine | v
taught to and practiced by any health practitioner who has a background in the basic medical sciences
and clinical practice, and it can adapt quickly and easily to emerging evidence. It can also provide a
common language and shared principles, organizing tools, and analytic process to support and facilitate
integrated health care.
Continuing the Journey
We nd ourselves at the beginning of the 21st century faced with a health care system in disarray on
many levels. We must reassemble the disparate pieces of this bafing puzzle into a new and more coherent
pattern (a new operating system). The intention of this document is to establish the need for a new
model of care, and to make conscious, transparent, and usable the functional medicine model
and our methods of teaching. We will show how this integrated model can better meet the needs of a
population aficted with steadily increasing rates of chronic disease. We believe that these changes will
also help physicians establish a more satisfying basis for clinical practice.
The diligent work and thinking of 20th century clinicians and scientists have brought us to this moment
with many tools and key concepts, including:
the art and science of clinical medicine
systems biology and personalized, systems medicine
prospective health care
patient-centered health care
the chronic-care model and the chronic-care team
integrative medicine
nutrigenomics, pharmacogenomics, proteomics, metabolomics
evidence-based medicine (EBM)
right and left brain functionality and the healing partnership
the science and practice of creating insight as part of the therapeutic encounter
the process of managing the uncertainty inherent in the clinical encounter
We will explore all of these topics in the following pages, and we will address the challenge of synthesizing
a model of health care for the 21st century that cogently integrates the best components of both
established and emerging knowledge and practices. We will describe a model for therapeutic relationships
that enhances the emergence of a healing partnership, that engages all parts of the brain, and that
strengthens the bodies, minds, and spirits of both physicians and patients as they share the path toward
improved health.
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21st century medicine:
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Our heartfelt thanks to the Bitzer Family
and the Fountainhead Foundation
for the ongoing support
that has made this project possible.
David S. Jones, MD
President, The Institute for Functional Medicine
Laurie Hofmann, MPH
Executive Director, The Institute for Functional Medicine
Sheila Quinn
Consulting Author and Editor
21st Century Medicine | vii
21st
century
medicine:
A New Model for Medical
Education and Practice
Foreword
________________________________________
21st Century Medicine:
A Gift to Our Patients and Our Students
As we see our healthcare system falling to pieces in front of us, we must ask some
key questions. What is wrong with our views of health, disease, and the provision
of care? Why does something that costs so much yield so little for so many? How
can we best bring the science and art of medicine to our communities for the
greatest good?
Framing this discussion are two very different hypotheses:
1 Advances in medical science and technology will solve all of our personal and global health
needs.
2 Natural healing techniques are safer and more effective than drugs and surgery.
Between these two points of view, both idealistic persuasions but starry eyed,
is a reality about the future of medicine. This vision is well articulated in the
monograph, “21st Century Medicine: A New Model for Medical Education and
Practice,” by David Jones, Laurie Hofmann, and Sheila Quinn.
The eld of functional medicine offers educators, clinicians, and researchers
a scientically valid semantic and conceptual bridge between the benets of
hard sciences, clinical medicine and integrative practices. Evolving sciences
such as genomics, pharmacogenomics, and nutrigenomics offer innovative and
promising medical treatments. At the same time, the common sense application
of prevention, wellness promotion, improved lifestyle, diet, the use of botanicals
and nutritional supplements, mind-body therapies, and other complementary and
integrative approaches can be blended with these sciences through the Functional
Medicine Matrix Model™ approach.
This synergy can not only improve our health as individuals and communities,
but can close the maw of the gluttonous economic pit that excessive application
of medical technology with its “Fix me; I’m broken” paradigm provides to us.
Indeed, much of the resistance to changing medicine to a more integrative
approach has been rooted in the absence of a common language encompassing
what doctors learn to speak during medical school, or in other types of healthcare
training programs, and the varied landscapes of complementary and integrative
theories and practices.
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21st century medicine:
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This new model, as discussed in the monograph, offers cutting-edge systems biology, synthesized with
whole-person medicine. This is the best of both worlds. No longer is the patient seen purely through the
lens of a dysfunctional organ system, a disease, or a syndrome. By evaluating a matrix of root causes
in the diagnostic and therapeutic process, we open our eyes to a different altitude as well as latitude
of thinking about complex and chronic disease states. We can look further “upstream” to understand
the physiology and pathophysiology and not simply treat the end stage manifestations of that altered
physiology.
The Institute for Functional Medicine (IFM) is contributing to the development of medical school
curricula to introduce this higher level of reasoning and assessment. IFM has supported a number of
academic initiatives to expand the view of the patient from linear cause and effect, symptom and diagnosis
to a broader, real-life phenomenological perspective.
Traversing the view of function, health, and disease from the molecular and genomic to the psychosocial,
cultural, and behavioral has always been a breathtaking stretch of mind and consciousness. Bringing this
into medical training is particularly challenging even though it offers the opportunity to both respect our
students as persons and adult learners, and to meld their interest in science with their desire to heal. It
is a way to create a reciprocal languaging that provides bridges between learners and their patients as
well as with their colleagues. This language, embedded with the various functional medicine constructs,
expands our ability to communicate and to contextualize our own and our students’ understanding of the
underlying science of medicine with the art of healing.
Since our work involves training medical students and residents for practice, we have given much thought,
as have the authors of this monograph, to the future of medicine. To conclude we offer some comments
we think mirror the authors’ vision in both spirit and values.
The doctor of the future will be an integrative healer whose practice differs in many ways from that
of today’s typical physician. The doctor of the future will provide care that is patient-centered and
comprehensive (body, mind, and spirit), care that is both high-tech (using genomic prediction tools,
systems biology, and functional medicine, for example) and high-touch. Care will focus more extensively
on preventing disease and injury. The practice of the future will be provided by smoothly working teams
that will include primary care physicians, complementary and alternative health practitioners, health
coaches, and wellness mentors, as well as medical specialists, allied health and nursing practitioners.
Putting the patient in the driver’s seat allows representatives from any number of disciplines to serve as
navigator through the healthcare system, helping people sort through conicting data as well as the many
difcult choices they must make during their lives in times of both wellness and illness. Tomorrow’s
physicians will consistently assess new evidence, to ensure that their practices meet the highest standards
of quality and patient outcomes.
To a great degree, the body has the capacity to heal itself; this concept, in some ways, opposes the
mechanical model in which doctors act as xers. One goal of future practitioners will be to guide and
empower patients toward self-healing. Consonant with this approach will be use of prevention and health
promotion, the full range of natural treatments, use of the safest and least expensive interventions rst,
and also the mobilizing of community and social support for healthy living. This vision of the future
doctor does not reect a purely in-the-clinic model. Future clinicians, if they are to be integrative healers,
need to be out where people are and to participate in social and environmental policy change.
21st Century Medicine | ix
FOreWArd
As both medicine and medical education evolve in this century, as health care and healthcare reform
take shape, we believe that the concepts developed in this monograph will lead the way in thinking and
practical application. Integrative Medicine is dened as the practice of medicine that reafrms the importance of
the relationship between practitioner and patient, focuses on the whole person, is informed by evidence, and makes use of all
appropriate therapeutic approaches, healthcare professionals and disciplines to achieve optimal health and healing.1 As such,
this model of care partners closely with the approach taken in functional medicine to bring the best of our
thinking and practice to the bedside and to the community.
The Functional Medicine Matrix Model™, as elucidated in this paper, is an essential architecture for the
kind of medicine of the future we see both as imminent and necessary.
Victor S. Sierpina, MD
Chair of the Consortium of Academic Health Centers for Integrative Medicine
Galveston, Texas
Adam Perlman, MD, MPH
Vice Chair of the Consortium of Academic Health Centers for Integrative Medicine
Newark, New Jersey
1Consortium of Academic Health Centers for Integrative Medicine denition of Integrative Medicine.
http://www.imconsortium.org
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21st
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Education and Practice
Executive Summary
________________________________________
In early 2009, an extraordinary degree of public attention was focused on
healthcare reform. In Washington, DC, two hearings were held before the
Senate Committee on Health, Education, Labor and Pensions, and the Institute
of Medicine of the National Academy of Sciences hosted a Summit on Integrative
Medicine and the Health of the Public. In New York City, a major conference on
Integrative Health Care was held. The January/February 2009 issue of Health
Affairs was devoted entirely to The Crisis in Chronic Disease. Why?
We know with certainty now that rapidly rising rates of complex, chronic disease
are creating an unsustainable burden on the national economy in both direct (e.g.,
treatment) and indirect (e.g., lost productivity) costs.7 The $1.3 trillion estimated
to be the cost of chronic disease today may well grow to $4.2 trillion within
15 years.8 Health professionals struggle every day to cope with the increase in
suffering and disability that accompanies this modern epidemic. At a time when
many other urgent pressures on the national economy command our attention,
we absolutely must sustain our focus on the system-wide changes in health care
that will be required in the years ahead if the most severe consequences of this
epidemic are to be avoided.
A careful examination of the evidence on both performance and costs in
American health care convincingly demonstrates the urgent need for this
transformation. We have been taught to believe that we have the best health
care in the world, but the facts do not support such an assessment. We spend
about twice as much per capita as other industrialized countries and yet we rank
shockingly low on most parameters of health.9
Many diverse inuences are responsible for the current state of the public’s health
(see Figure 1).10, 11, 12 It is not enough, however, to demonstrate, as many experts
have done, that the majority of today’s chronic diseases could be prevented or
ameliorated by changes in lifestyle,13 and then suggest that patient responsibility
and self-care can take care of the problem. We must also ask what contributes
to such unhealthy lifestyles and how can we best equip clinicians to serve the
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patients who are living every day under those pressures. It is critical that we understand how great a
proportion of environment and lifestyle is inuenced by conditions beyond the control of individual
patients—not only the genetic vulnerability one is born with, but increases in environmental toxicity,
the homogenization and denaturing of the food supply, the inuence of sedentary technology on jobs,
education, and entertainment, the powerlessness and despair of poverty, the debility produced by chronic
stress, and the fragmentation of family and community life that leads to isolation and a lessened sense of
purpose and meaning. These are all complex problems that took many decades to create and that will
require a long-term national effort and effective leadership in public policy to alter. We recognize—and
emphasize—that not only must we change healthcare and medical education (the primary focus of this
paper), but over the next decades we must also change the practices and priorities of our political, social,
and economic structures to achieve fundamental change in the public’s health.
Figure 1: Major Influences Contributing to the Epidemic of Chronic Disease
In order to change our future, however, we must thoroughly understand our past. Therefore, after
presenting an overview of the paper (Chapter 1), we focus rst on exploring the dominant inuences that
have helped to shape the current crisis in health care (Chapter 2). Next, we present and discuss the most
prominent models that have been proposed for the future (Chapter 3). The implications of these issues
Aging
population
Chronic
Disease
Epidemic
Nutrition
(food supply,
dietary habits)
Chronic stress
Fragmented
families,
communities
Environmental
toxicity
Sedentary
lifestyles
(young and old)
Indoor living
(? vitD)
Poverty
Uninsured
Aging
population
eXecutiVe summAry
21st Century Medicine | xiii
for the practicing clinician are then analyzed (Chapter 4). And last, a preferred model for 21st century
medicine is presented (Chapter 5). It is important to recognize that even if patients do everything it is
possible for individuals to do for their own health (an idealized state that is highly unlikely to be realized),
we still have tens of millions of people with multiple chronic diseases, and well over 100 million with
at least one,14 and both gures are on the upswing. All of these people need more effective therapeutic
services, and everyone needs more effective disease prevention and wellness promotion strategies in order
to cope with the pervasive environmental inuences that make achieving health such a challenge.
The transformation of 21st century medicine from the prevailing acute-care model to a far more effective
chronic-disease model will succeed only if we attack the underlying drivers of the epidemic—the complex,
lifelong interactions among lifestyle, environment, and genetics—and if we engage the entire healthcare
system in a concerted effort to implement a unied, exible approach that can readily adapt to shifting
needs and emerging evidence. The central purpose of this paper is to demonstrate that such changes are
urgently needed and achievable.
In order to accomplish such an ambitious goal, several key objectives must be achieved. As discussed in
the succeeding pages, these include:
1. A shared understanding of the powerful, primary inuence of lifestyle and environment upon
genetic vulnerability in the initiation and progression of chronic disease must be matched with a
therapeutic tool kit that reverses the trajectory toward disease and disability, promotes health, and
empowers patients as full partners in the lifelong pursuit of wellness.
2. A more balanced perspective on the appropriate uses of both evidence and insight must be
integrated with broad-based clinical skills to establish the foundation for healing partnerships
between practitioners and patients.
3. A common set of principles, concepts, and practices that can be used by all health professionals
must be taught and applied in clinical practice so that well-trained integrated healthcare teams
can be deployed appropriately.
4. A model that incorporates all these elements must pervade education, clinical practice, and
research in both private and public arenas.
In this paper, we propose that functional medicine exemplies the systems-oriented, personalized medicine
that is needed to transform clinical practice, education, and research. The functional medicine model of
comprehensive care and primary prevention for complex, chronic illnesses is grounded in both science
(the Functional Medicine Matrix Model™; evidence about common underlying mechanisms and pathways of
disease; evidence about effective approaches to the environmental and lifestyle sources of disease) and art
(the healing partnership and the search for insight in the therapeutic encounter). Many years of developing,
writing about, and teaching this model to thousands of clinicians in both private practice and academic
medicine have demonstrated that functional medicine can enable us to reshape health care for the
demands of the 21st century. Using this approach, a healing partnership between doctor and patient can
ourish, new and useful insights can be achieved, and a broad array of assessment and therapeutic tools
can be utilized by integrated healthcare teams.
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21st
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medicine:
A New Model for Medical
Education and Practice
Chapter 1
_______________________________________
Introduction
Opportunity
If done right, the development of a health care system that focuses on personalized health
planning will be every bit as transformational as the coupling of science to medicine was in the
early 20th century.
—Ralph SnydeRman, md, and R. SandeRS WilliamS, md15
Throughout the medical system, the heartbeat of impending change has been
heard with increasing intensity since the turn of the century. Concepts such
as prospective health care, personalized medicine, systems biology, nutritional
genomics, integrative medicine, the chronic-care model, and others represent
diverse aspects of the impetus to devise a substantively different way of
approaching health care in the 21st century. The shift in prevalence from acute
to chronic disease16, 17 and a growing recognition of the inherent limitations
and consequences of shaping medicine primarily around an acute-care model18
are among the most powerful forces that are driving change. The context of
uncertainty that pervades the realm of clinical care19 demands a comprehensive
and exible model that can integrate evidence relevant to the individual without
forcing physicians and other practitioners to manage complex, chronic disease
using an acute-care model that is ill-suited to the task. Transformation is
imminent—the opportunity is now.
The “next next transformation” will change the paradigm to focus on health—positively dened
and measured as something other than the “absence of disease”; conceived as an integrated
function of biology, environment, and behavior; and measured as a product of physical, mental,
social, and spiritual variables.
—michael JohnS, md, and Kenneth BRigham, md20
As we come to the close of the rst decade of the 21st century, the opportunity
to inuence the strategic decisions that will redirect medical education and
practice for the foreseeable future will encounter many challenges. Philosophies
of health and disease, exciting new models of delivery and management of care,
practitioner diversity and interrelationships, emerging perspectives on science
2 | 21st Century Medicine
21st century medicine:
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and evidence, and the teaching of analytical thinking and clinical reasoning are all under pressure to
evolve. Resistance to change and eagerness for it exist simultaneously within all established systems; both
perspectives represent important issues that must be addressed successfully to ensure that changes are
purposeful, practical, and effective. Educational programs and leaders will be called upon to set the pace
of change, identify the best models, integrate those models into existing curriculums, and advocate for
widespread adoption.
We can facilitate this process by taking into account the substantial common ground that already exists
among many of the leading innovative paradigms, even when they are not directly comparable in intent
or in practical applications. Congruent elements can be identied, extracted, and synthesized to inform
a comprehensive new model that will be compatible with both established and emerging approaches to
health education and practice. In addition, there are important principles and practices that can provide a
solid foundation for synthesizing these congruent elements into a workable new model.
Visualizing and implementing a fresh approach to health and disease will require collaborative efforts
and systems that work to the benet of patients and practitioners alike. In this paper, we will describe
how certain key forces and concepts are critical components of a dedicated effort to achieve productive
and lasting improvements in our healthcare system. We will demonstrate how the common themes in
these overlapping paradigms represent fertile terrain for synthesizing a comprehensive new model. We
will identify elements that must be added to the common themes to create an effective model for teaching
and practice. And we will describe that new model and advance suggestions about how to strengthen
and implement it. The ideas are (metaphorically) bursting out of the literature, essential tools are being
developed, and the pivotal technologies are rapidly advancing—the moment is ripe with promise.
Purpose
Our overarching purpose in writing this paper is to illuminate a path toward health and vitality for
patients—not an easy or straightforward task in a world of increasing complexity and epidemic levels
of chronic disease (Chapter 2). The intention of this document is to establish the need for a new
model of care and to make conscious, transparent, and usable the functional medicine model.
We offer to academic medicine leaders, practicing physicians, and other health professionals a model that
we believe will substantially improve management of disease risk and assessment—as well as treatment for
the millions of patients who already suffer from complex, chronic disease—using personalized, systems-
oriented, cost-effective approaches. Blending the foundational principles and practices of functional
medicine with the substantial common ground that already exists in emerging models claries a more
comprehensive and effective model of teaching and practice for medical schools, residency programs,
and eventually other health profession schools. Such an ambitious goal will succeed only if the plans rest
upon a solid foundation that resonates strongly with leaders and early adopters in medical education and
the health professions. Strategic objectives and effective tools to guide action steps appropriately will be
required. The need for change and the matching of solutions to problems must be clear and persuasive.
This paper will analyze emerging trends and needs and address the power of this synthesized model to
shape those trends and meet critical needs in order to help improve the education and effectiveness of
healthcare practitioners and offer their patients a better path toward lifelong health.
21st Century Medicine | 3
intrOductiOn
Emerging Models
From among the creative and fascinating new paradigms, we will address six that have emerged as leaders
and already claim many adherents. They share a great deal of common ground that is critical to a
synthesized, comprehensive model for 21st century medicine. Each of these new models, while incomplete
in itself, contains elements that help to ensure compatibility and integration into an overarching approach.
These will be discussed in much greater detail in Chapter 3, but here we introduce the key concepts of
each model. (There are other models of note, of course, including the Future of Family Medicine project
and the Medical Home project; information on both of these is provided in the Appendix. In the body
of this paper, however, we have narrowed our discussion to the models that appear to have the greatest
potential impact on the actual content of care, rather than the structure of care.)
A graphic representation of some of the common themes and key concepts in these six models can be
seen in Figure 2.
GOAL:
Comprehensive
21st Century Medicine
NEEDED:
Synthesized Model for
Teaching and Practice
with
Common language, principles
Practical tools
Personalized Medicine
Genetic vulnerabilities
Environmental influences
Reduce adverse
drug effects amd interactions
Informed by
evidence
Evidence-based
Medicine
Best: “green medicine”; clarifies
mechanisms and actions
Worst: rigidity; focus on drug solutions;
failure to use adaptive unconscious in the
context of uncertainty; failure to match
RCT outcomes to individual patients
Prospective Health Care
Multidisciplinary team-based care
Patient self-management
Personalized medicine
Systems biology
Informed by evidence
System-wide change
Systems Biology
Multidisciplinary
Personalized medicine
Underlying mechanisms
Informed by evidence
Chronic Care Model
Multidisciplinary
team-based care
Patient self-management
System-wide change
Informed by EBM
guidelines
Integrative Medicine
Multidisciplinary
Practitioner-patient relationship
Diverse approaches
Whole person focus
Informed by
evidence
Applies most current research on
therapeutics and diagnostics to patient care.
Applies knowledge of genetic
individuality to improve diagnostics and
therapeutics; pharmacogenomics
Adopts best of CAM;
collaboration
with CAM providers;
importance of mind/body
Prepared, proactive
practice team; informed
activated patient;
decision support; clinical
information systems;
delivery system design;
patient self-management
Prediction, prevention,
personalization, participation;
pharmacogenomics
Prediction, prevention,
personalization, participation;
pharmacogenomics
Figure 2: Common Themes and Key Concepts Among Emerging Models
in Medical Education and Clinical Practice
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21st century medicine:
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1. Personalized medicine
Personalized medicine is often rather narrowly dened to comprise primarily the development
of genetic tests to identify risk factors for adverse or unpredictable drug effects and to identify
individuals who are most appropriate for certain kinds of drug therapies or diagnostic
procedures.21, 22 This kind of assessment should certainly help to improve the matching of drugs
and diagnostics to individual patients and, as a result, may also help to reduce death, disability,
and costs associated with individual differences in the biotransformation of drugs and other
substances.23 However, under the rubric of personalized medicine lie many other complex issues
relevant to biochemical, physiological, genetic, and environmental individuality that must also
be attended to if we hope to reverse the modern epidemic of chronic disease and assist patients
toward healthier lives. This broader model of personalized care has already become an explicit
component of systems biology and prospective health care, and it is implicit in the chronic-care
model and integrative medicine as well. Personalized medicine is critical to the future of health
care.
2. Prospective health care
A bold new model for 21st century medicine called prospective health care was proposed in
2003 by Snyderman and Williams.24 Pilot projects have been initiated and are being tested now
at Duke University. In a 2006 article,25 Snyderman and Langheier described their rationale in
terms completely consistent with the focus of functional medicine for the past two decades:
Chronic diseases develop as a consequence of an individual’s baseline susceptibility coupled
with their exposure to environmental factors. These may trigger initiating events, leading to
the accumulation of pathological changes and the onset and progression of chronic disease.
Today, most health-care expenditure is focused on the later stages of this process, long after
the development of many underlying pathological changes. Until recently, it could be argued
that the focus on treating disease was justied because the ability to predict, track, and prevent
its onset was not technically feasible. This is no longer the case, and the emerging sciences of
genomics, proteomics, metabolomics, medical technologies and informatics are revolutionizing
the capability to predict events and enable intervention before damage occurs. Personalized
risk prediction and strategic health-care planning will facilitate a new form of care, which we
have called “prospective health care.”
Including the same four elements as systems biology (prediction, prevention, personalization, and
participation), prospective health care offers a much broader perspective, describing structural and
procedural transformations that must also occur in reimbursement, research, risk management
assessment, record keeping, and the delivery of care.26 The thrust of these changes is “toward
managing disease risk and providing personalized care for chronic and acute disease.”27
21st Century Medicine | 5
intrOductiOn
3. Chronic-care model
The full chronic-care model (CCM), rst conceived in 1993, was formally presented in a 2001
publication by Wagner et al.28 Since that time, it has undergone serious study, implementation,
and revision to accommodate experiences in clinical settings and ndings from research.
Emerging evidence has shown fairly conclusively that patient outcomes in a variety of chronic
conditions can be improved whenever substantive progress is made on integrating the elements of
this model into clinical practice. Core elements include:
Productive interactions between informed, activated patients and prepared practice teams
Effective patient self-management strategies
Delivery system redesign (team approach; multidisciplinary, planned interventions instead of
acute, reactive interventions; use of case managers; regular follow-up)
Decision support (integration of evidence-based guidelines into the ow of clinical practice so
that information to support clinical decision making is readily available)
Clinical information system (the use of a database and other resources that bring timely,
relevant information to both physicians and patients)
Community resources and policies
CCM has in common with prospective health care a strong emphasis on redesigning the systems
that support and shape clinical practice. Both have explicit emphases on a team approach to
chronic care, the necessity of patient self-management, and the urgent need to involve community
resources and attract the attention of policymakers.
4. Evidence-based medicine
Evidence-based medicine (EBM) is “the conscientious, explicit, and judicious use of current best
evidence in making decisions about the care of individual patients. The practice of EBM means
integrating individual clinical expertise with the best available external clinical evidence from
systematic research.”i
We include EBM in the analysis of emerging models because of its growing inuence on clinical
practice and medical education. Although it is not, in and of itself, a type of medical education or
clinical practice, at its best it can provide practitioners and healthcare delivery organizations with
more current and focused decision support through the integration of relevant research ndings
into clinical decision making. Although EBM is intended to reduce uncertainty and improve the
consistent use of best practices in patient care, experimental designs have not yet caught up with
the complexity of chronic disease, the multiple needs and diverse presentations of patients in the
clinical setting, and the multifactorial interventions that are required to address such diversity and
iUsed with permission of the Centre for Evidence-based Medicine. A more expanded denition of Evidence-based medicine is
included in the Appendix.
6 | 21st Century Medicine
21st century medicine:
A New Model for Medical Education and Practice
complexity.29 EBM cannot replace analytical thinking, clinical reasoning, and clinical experience,30
although sometimes it is presented as doing just that. Improperly applied, EBM can place patients
in serious jeopardy.31 Ideally, it can be used to increase practitioner effectiveness if its strengths are
appropriately utilized and its limitations are clear: “The methods of EBM do not supply ‘correct’
answers but rather information that can improve clinical judgment.”32 Ultimately, the appropriate
use of EBM relies on a more precise denition of what constitutes relevance and best evidence for
each individual patient encounter.
5. Systems biology
The Institute for Systems Biology in Seattle, Washington, identies four factors that comprise
its eld: prediction, prevention, personalization, and participation. Although elsewhere systems
biology is not dened quite so broadly, it is useful to consider it through this wide-angle lens,
for it makes readily apparent the interconnections with integrative medicine, prospective health
care, and personalized medicine that open the door to a synthesized model. Systems biology as
currently pursued focuses primarily, as does personalized medicine, on genetic mechanisms in
drug responses, but given a broad vision—and the will and funding to execute on that vision—it
could become the scientic engine driving clinical medicine toward the model we are proposing.
A more detailed description from the Institute for Systems Biology’s Web site is provided in the
Appendix.
6. Integrative medicine
In the years since 1999, when eight academic medical institutions rst met to discuss the emerging
eld of integrative medicine, active participation among academic medical centers has grown
dramatically. Now more than 40 institutions are members of the Consortium of Academic
Health Centers for Integrative Medicine (CAHCIM), comprising many of the nest medical
schools in the country, with several having endowed centers or foundations to support expanded
development in the eld. Their collective mission is:
…to help transform medicine and health care through rigorous scientic studies, new
models of clinical care, and innovative educational programs that integrate biomedicine,
the complexity of human beings, the intrinsic nature of healing and the rich diversity of
therapeutic systems.33
Their denition of integrative medicine is:
…the practice of medicine that reafrms the importance of the relationship between
practitioner and patient, focuses on the whole person, is informed by evidence, and makes use
of all appropriate therapeutic approaches, healthcare professionals and disciplines to achieve
optimal health and healing.
iiSee list of CAHCIM members in the Appendix.
21st Century Medicine | 7
intrOductiOn
Several elements of integrative medicine are highly relevant to the model proposed in this paper:
The openness to new diagnostic and therapeutic strategies (e.g., nutrients, botanicals, mind-
body interventions, acupuncture) and to cooperation with health professionals from other
disciplines signals an important readiness to develop a fully integrated healthcare model—one
in which the patient is the central focus and all practitioners have in common certain critical
elements of language, philosophy, and clinical practice.
The commitment to adopt innovative approaches in education is essential to the
transformation of medicine.
The emphasis on the value of practitioner-patient relationships and the focus on the whole
person will play a signicant role in the medicine of the future. These values—formerly so
intrinsic a part of medicine that they went almost unnoticed—are receiving renewed attention
now that their disappearance from much of medical care has become apparent. They are
absolutely vital components of a transformed approach to health care.
Summary
In this white paper, we will establish the need for a new model of education and care; we will address
forces that may represent obstacles to change; and we will explore the key concepts and elements already
present in science and medicine that are ripe for synthesis into a new, more comprehensive model.
Our goal is to make improvement in medical education programs and clinical practice feasible – not
in an abstract or ideal sense, but in the real world with all its resistance to change and discomfort with
emerging concepts. To that end, funding has already been secured for the development of a pilot project
for adapting the model to medical education. Before being nalized, each phase of the project will be
reviewed by a small group of leaders within academic medicine who are interested in achieving a major
shift in medical education, so that we tailor our recommendations to the audience with as close a t as
possible. Our aim is nothing short of inspiring system-wide change—the transformation of medicine is
imminent, it is urgently needed, and it is entirely possible.
21st Century Medicine | 9
21st
century
medicine:
A New Model for Medical
Education and Practice
Chapter 2
_______________________________________
The Changing Medical Environment
Background
There are, literally, innumerable facts and statistics available with which to
describe and analyze health and health care. Any discussion must of necessity
be based on a selected subset of the data and, thus, subject to the bias of the
authors. We have, for example, omitted such critical issues as the reimbursement
structure, governmental regulatory inuences, health disparities, environmental
degradation, and the uses of technology—all topics on which reams of important
material have been written. Our goal here is not to cover everything that is either
problematic or of value within the medical environment, but to concentrate
our thinking on well-established data that help to illuminate an overarching
problem—that we are losing the battle against chronic disease and that
fundamental change will be required to improve our performance.
Global and economic issues
The healthcare system is inuenced by increasingly complex and varied issues.
Although many of these are beyond the scope of this paper, we would be remiss
if we did not at least acknowledge their importance:
The growing ethnic diversity of the U.S. population poses challenges
of communication, varied beliefs and preferences about treatment,
and the adverse impact of the standard American diet (SAD)
on genetically vulnerable populations. [An excellent overview
of emerging global health issues that are brought to the U.S. by
immigrant populations can be found in the July/August 2008 issue
of Health Affairs, which focuses on India and China. These articles
demonstrate unequivocally that health issues in the developing
countries parallel those of the developed world, as afuence,
sedentary lives, and fragmentation of communities increase while
food quality and diversity decrease.]
21st century medicine:
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10 | 21st Century Medicine
The transmissibility of new diseases (e.g., avian u) between species and across the world’s
continents poses a special challenge to both acute and chronic care.34
Economic shifts that are strongly affected by global markets could have profound effects on the
U.S. model of healthcare nancing, an issue that has been under considerable scrutiny for many
years already. Increasingly, the evidence identies our patchwork approach to reimbursement as
a considerable barrier to equitable and effective care.35
Importation and transportation of foods, prescription drugs, botanicals, and nutraceuticals
among countries with widely differing quality control and environmental standards will affect
virtually every citizen over time.
While we focus in this paper on models for clinical practice and medical education, we should keep the above
issues in mind, because they will continue to inuence both the healthcare system and individual health.
The pharmaceutical and acute-care models
The acute-care model is characterized by rapid differential diagnosis aimed at prescribing a drug (or
procedure) that will ameliorate the patient’s presenting symptoms and avert the immediate threat.36 It
minimizes the involvement of the patient, who functions as a mostly passive recipient of the procedure or
prescription.37 It is not a model that reimburses the practitioner for looking into why the patient became
ill, or whether she/he will be back many times for ramications of the same underlying problem.38
Instead, it prioritizes quick solutions to the most pressing problems. It is, of course, absolutely essential
in emergency and hospital-based care, but difculties arise when this model is applied to ongoing,
community-based care, a process that accelerated under the managed-care movement (which turned
Acute-care model
Pharmaceutical and surgical answers
Antibiotics,
pain relief,
cancer,
contraception,
surgical
advances
Trauma
Acute
infections
Pharmaceutical
profits
Surgery profits
Managed care
Drug advertising
Dangerous
working
conditions
Endemic
poverty
Poor public
hygiene,
sanitation
Ignorance
about germs
20th Century Medicine
Figure 3:
Forces Narrowing the Focus of 20th Century Medicine
21st Century Medicine | 11
out to be far more about managing costs than managing care)
and the direct-to-patient advertising of drugs. With hindsight, it
seems as though everything has been pushing the system toward
this narrowed focus, regardless of t (Figure 3).
The advances achieved by drugs in curing acute infections and
managing some of the most threatening diseases mankind has
faced were dramatic in the last century. The extended romance
with pharmaceutical medicine, which rst blossomed in the
early 1930s when penicillin began to cure previously intractable
infectious diseases, has now dominated medicine and medical
education for more than seven decades. From depression to
diabetes, from heart disease to asthma, the search for therapeutic
compounds that can be patented as drugs continues unabated.
The accompanying nancial incentives have attracted (and
perhaps distracted, see Sidebar) some of the best minds and
most inuential leaders in research and medical education,
including those engaged in the development of systems biology
and personalized medicine, both of which are primarily focused
on pharmacogenomics at this time (see Chapter 3 and the
Appendix for more information on these models).
Costs and Performance in
the Battle for Health
It is discouraging to note that among the vast array of peer-
reviewed medical research reports published every year, there
is so little that addresses whether the overall health of the
population shows an adequate positive response to current
medical treatment. Thousands upon thousands of studies
compare one drug to another without ever acknowledging
that Americans are far less healthy—at far greater cost—than
their counterparts in the rest of the industrialized world.
The reduction in deaths from, for example, heart disease is
emphasized,45 while the fact that we have failed to prevent
CVD—even while reducing, through drugs, the prevalence of
CVD risk factors such as hypertension and high cholesterol46—
is too often ignored. In fact, we must turn primarily to
philanthropic or governmental agencies for data and analyses
that reveal the scope of the failure. “The Milken Institute
recently estimated that the most common chronic diseases cost
the economy more than $1 trillion annually, mostly from lost
Research Bias: The
Pharmaceutical Hegemony
in Funding and Focus
Opportunities lost are perhaps the
greatest concern in the dominance of
the pharmaceutical research model.
Too often, the search for drugs that will
pay off for investors and executives of
pharmaceutical companies determines
the research agenda. Rather than being
driven by patient needs, public health
priorities, or scientic curiosity about
mechanisms and pathways, the prot
motive is the driver of the research
agenda,39 and the gains to science and
health are collateral outcomes, not
central purposes. Lest we think this is
trivial, consider that 70% of the money
for clinical drug trials in the U.S. comes
from the pharmaceutical industry.40
“Scientically, a neutral or negative
trial is as valuable as a positive one,
although commercially this is clearly
not the case.”41 Unless all results are
available to the scientic community,
the evidence record about those drugs
that are investigated can be signicantly
skewed by the absence of negative or
neutral ndings. The value to academic
researchers (and their institutions) of
bringing in large clinical trials with
drug company funding may be very
signicant; promotions, recognition,
and supplemental income provide a
triple-threat incentive that is virtually
impossible to ignore when considering
research priorities.42, 43
Many studies have shown a bias toward
positive results when the research was
funded by the drugs’ manufacturers.44
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worker productivity, which could balloon to nearly $6 trillion by the middle of the century.”47 If nothing
else, that estimate alone should galvanize us to action!
The broad education in science and clinical arts that physicians experience today is expressed in clinical
practice through a constricting and linear process that is primarily aimed at naming a drug of choice for
the patient at hand.48 Unfortunately, 50 years of such practices have failed to stem the rising tide of chronic
diseases among both young and old,49 while related problems have emerged to cause great concern:
The cost of care is unmanageably high and rising,50 driven by the high costs of
hospitalization51 and drugs,52, 53 but also fueled by increasing prevalence of complex, chronic
disease at all ages of the population.54, 55 It is estimated, for example, that more than half of
all Americans suffer from one or more chronic diseases,56 and that the 8 million Medicare
beneciaries who have ve or more chronic conditions accounted for over two-thirds of the
program’s $302 billion in spending in 2004.57
The Milken Institute report, An Unhealthy America (October 2007), provides the
following food for thought:
To quantify the potential savings from healthier lifestyles and plausible but modest
advances in treatment, we compared a “business-as-usual” baseline scenario with
an optimistic scenario that assumes reasonable improvements in health-related
behavior and treatment. The major changes contemplated here are weight control
combined with improved nutrition, exercise, further reductions in smoking, more
aggressive early disease detection, slightly faster adoption of improved therapies,
and less-invasive treatments….
Across the seven diseases, the optimistic scenario would cut treatment (direct) costs
in 2023 by $217 billion…. And the cumulative avoidable treatment costs from
now through 2023 would total a whopping $1.6 trillion. Note that this would be a
gift that keeps on giving, saving hundreds of billions annually in the years beyond
2023.
All told, our analysis implies that modest reductions in avoidable
factors—unhealthy behavior, environmental risks, and the failure to
make modest gains in early detection and innovative treatment—will
lead to 40 million fewer cases of illness and a gain of over $1 trillion
annually in labor supply and efciency by 2023. Compared to the costs we
project under the business-as-usual scenario, this represents a 27 percent reduction
in total economic impact.
Table 1 displays the bookends of health: rankings on infant mortality and life
expectancy. The U.S. makes a very poor showing on both, particularly for a country
whose citizens have been taught to believe they have the best health care in the world. The
U.S. spends twice the median per-capita costs calculated by the Organization for Economic
Cooperation and Development (OECD),58 has extraordinarily poor outcomes for such a
massive investment,59 and does not even provide coverage for all its citizens (an estimated 47
million currently uninsured60; 75 million under- and uninsured combined61).
21st Century Medicine | 13
Table 1. Infant Mortality and Life Expectancy Rankings of the United States
Ranking Country Infant
Mortality1Country Life
Expectancy2Ranking
1 Sweden 2.8 Japan 81.4 1
2 Japan 3.2 Switzerland 80.6 2
3 Finland 3.5 Sweden 80.6 3/4
4 Norway 3.6 Australia 80.6 3/4
5 Czech Republic 3.9 Canada 80.3 5
6 Germany 4.1 Italy 79.9 6/7
7 France 4.2 France 79.9 6/7
8 Spain 4.3 Spain 79.8 8
9 Switzerland 4.3 Norway 79.7 9
10 Austria 4.5 Israel 79.6 10
11 Denmark 4.5 Greece 79.4 11
12 Australia 4.6 Austria 79.2 12
13 Canada 4.6 New Zealand 79.0 13/14
14 Portugal 4.9 Germany 79.0 13/14
15 United Kingdom 5.0 United Kingdom 78.7 15
16 Ireland 5.2 Finland 78.7 16
17 Greece 5.3 United States 78.0 17/18/19
18 Italy 5.7 Denmark 78.0 17/18/19
19 New Zealand 5.7 Cyprus 78.0 17/18/19
20 Korea, South 6.1
21 United States 6.4
1. Infant deaths per 1,000 live births.
2. Life expectancy at birth, in years, both sexes.
Source: U.S. Census Bureau, International Database.
From: http://www.infoplease.com/ipa/A0004393.html
Information Please® Database, © 2007 Pearson Education, Inc. All rights reserved.
The “quick x” mentality that drug dependence has fostered in patients creates an
unhealthy cycle that drives further drug dependence. Sensible and distinguished voices calling
for major long-term investments in helping people establish healthy behaviors and in ensuring
a healthy planet have heretofore been mostly ignored in the struggle for attention and funding.
And yet, with only a few exceptions, the development of chronic disease is predominantly
inuenced by multiple interactions between genes and environment experienced over
many years; neither factor alone is enough—the genes must be plunged into an adverse
environment to express disease and they must be rescued from such environments to restore
health (not just suppress symptoms):
➢Walter Willett: “For most diseases contributing importantly to mortality in Western
populations, epidemiologists have long known that nongenetic factors have high
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14 | 21st Century Medicine
attributable risks, often at least 80 or 90%, even when the specic etiologic factors are not
clear.”62
➢Kenneth Thorpe: “Health behavior such as overconsumption of food, lack of exercise,
smoking, and stress accounts for 40% to 50% of morbidity and mortality.”63
➢Robert Heaney: “Discerning the full role of nutrition in long-latency, multifactorial
disorders is probably the principal challenge facing nutritional science today. The rst
component of this challenge is to recognize that inadequate intakes of specic nutrients
may produce more than one disease, may produce diseases by more than one mechanism,
and may require several years for the consequent morbidity to be sufciently evident to be
clinically recognizable as ‘disease.’”64
Drug-resistance phenomena,65 adverse drug reactions,66 and adverse interactions between
drugs and foods,67 drugs and botanicals,68 and drugs and other drugs69 now affect millions
of lives each year and are a cause of death in unprecedented numbers.70 Rates of visits to
provide care for adverse drug reactions increased by one-third between 2001 and 2004.71
On a deeper level, the drug paradigm—and the most rigid part of the evidence-based movement that
supports it—may adversely affect clinical judgment. To minimize time spent with patients, physicians
are forced to focus on prescribing the “right” drug. Very often, however, the evidence about the “right”
drug rests on studies that do not reect a real patient population as seen in clinical practice72; multiple
comorbidities, for example, are usually excluded from RCTs.73, 74 Until very recently, nearly all clinical
trials failed to account for variations in individual biochemistry and physiology, as well.75, 76
This shift toward rapid prescribing results in a de-emphasis on establishing therapeutic relationships and
exploring the patient’s story. Time pressures applied by reimbursement entities make it very difcult to
do the analytical thinking that develops broad pattern-recognition abilities. Immensely valuable clinical
skills for managing complex, chronic disease and multiple comorbidities are thus being sidelined; as that
happens, fears about innovation and creativity surface, a retreat to dogma and linearity becomes apparent,
and the idea that the job of medicine is to nd the right drug(s) for the most parsimonious diagnosis
preoccupies mainstream thought. Such forces separate the physician from many analytical and inferential
skills that are likely to be extremely useful in the search for common underlying pathways of chronic
disease and for new approaches designed to intervene where such disease actually originates—in the
patient’s unique mix of biochemistry, genetics, and environment.
The focus on drugs could be considered both cause and effect of the dominance of the acute-care model
that has come to characterize medicine today. As the challenges of infectious disease and trauma gave
ground to advances in drugs and surgery, startling successes strengthened the belief that modern medicine
would eventually conquer most diseases with those tools, a perspective that only intensied as the prots
to be made from drugs and surgery became a magnet for both individuals and institutions. Few scientists
or physicians in the 1950s and 60s foresaw a moment when the challenge of chronic disease would swamp
the healthcare system and prove resistant to the miracles of 20th century medicine.
21st Century Medicine | 15
Now, however, in the 21st century, we are fully aware that complex, lifelong interactions between
our genes and environmental degradation,77 unhealthy diets78 (fueled by changes in both eating
habits and food supply79), stress,80, 81, 82 sedentary lives,83 and social fragmentation of families and
communities84 have surged to the forefront as interwoven causes of chronic disease that are not
amenable to treatment with an acute-care model. (Figure 4 depicts the pressures that are forcing a
broader process of clinical thinking and care.) With an aging population, these effects are present through
many more years of life and thus become impressive cost drivers (see, for example, the Medicare data in
Figure 5). The system must expand to address these interconnected trends. Broad-based pattern-recognition
and communications skills will be needed to prevent, treat, and reverse the declining function associated with
these pervasive inuences. We must transform our system of health care through new models for medical
education, acute and chronic disease management, research, health insurance, and scal responsibility.
Genetics
Nutri-
genomics
21st Century Medicine
Nutra-
ceuticals
Botanicals
Meditation Prospective
medicine
and systems
biology Personalized
and
integrative
medicine Chronic-care
model and
risk
management
Empty
calories
Fast food
Over-
abundance
Lack of
exercise
Sedentary
home/
work lives
Lack of
support
Stress
Spirituality
Community
Environmental
level:
Pesticides
Toxic Waste
Urbanization
Population
level:
Aging,
Diversity
Globalization
Chronic care model
Prevention
Lifestyle modification
Patient education and empowerment
Lifestyle Changes
Figure 4:
Forces Expanding the Focus of 21st Century Medicine
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16 | 21st Century Medicine
The seemingly intractable poor performance of American medicine on a wide range of health
measures85, 86 forces us to pose some critical questions:
Does the investment in a paradigm that identies drugs as the treatment of choice across a
broad array of diagnoses still produce the same returns on investment that were achieved in
earlier decades?
Is a system that seeks to reduce doctor-patient face time to the fewest possible minutes, and
that measures effectiveness by how little time and money are spent, going to enable us to
address population-wide health needs in the century ahead?
Does the acute-care model respond appropriately to the needs of patients already suffering
from complex, chronic disease and multiple comorbidities, as well as to the exigency of
preventing those diseases for currently healthy people and future generations?
We suggest that not only is the evidence persuasive that the answer to those questions is “no,” but that
the continued almost exclusive reliance on pharmaceutical answers to an epidemic of complex, chronic
disease may constitute an unintended rejection of some practices critical to improving our response to
today’s urgent problems.
5+ Chronic Conditions
68% of Medicare Spending
4+ Chronic Conditions
12% of Medicare Spending
3+ Chronic Conditions
10% of Medicare Spending
2+ Chronic Conditions
6% of Medicare Spending
1 Chronic Condition
3% of Medicare Spending
0 Chronic Conditions
1% of Medicare Spending
Figure 5:
Medicare Spending as a Function of Number of Chronic Conditions
Data from Chronic Conditions: Making the Case for Ongoing Care. Johns Hopkins University and
The Robert Wood Johnson Foundation: Partnership for Solutions, September 2004.
21st century medicine:
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Changing Patterns: From Acute to Chronic Disease
The changes in mortality and morbidity in the United States over the last century have been described as a
shift from an age of “pestilence and famine” to an age of “degenerative and man-made diseases.”87 In other
words, infections and undernutrition as relatively straightforward causes of illness and (often early) death have
been overwhelmingly superseded by chronic, degenerative conditions caused by multiple, complex inuences.
In addition to the discovery and development of antibiotics, the great achievements of the public health
system88—vaccinations; safety in municipal water and sewage systems, foods, medicine, workplace, highways
and motor vehicles; prenatal and pediatric care; reduction in smoking—were among the most critical factors
in making this shift, particularly in the rst half of the 20th century.
Medicine’s focus on the development of a sophisticated and multifaceted pharmaceutical war chest to
cope with infectious disease achieved many notable successes. Unfortunately, infectious disease still has an
uncomfortable persistence—a way of breaking out in a different guise just when it was thought to be under
control—witness the emergence of AIDS, the ability of bacteria and viruses to become resistant to drug
treatments, and the ever-evolving inuenza virus, to name a few examples. There is no question, however, that
pneumonia, inuenza, tuberculosis, and diarrhea/enteritis (the leading causes of death in the United States
in the early 1900s) have been replaced by heart disease, cancer, and cerebrovascular disease at the top of the
mortality list.89
The tremendous advantage of this shift is that we can live much longer with chronic than acute
diseases.iii Cardiovascular disease (CVD), for example, is the biggest killer,iv even though three of its
four primary risk factors (hypertension, hypercholesteremia, smoking) have been signicantly reduced.90
Unfortunately, the fourth, diabetes, has increased.91 Pharmaceutical and surgical interventions have evolved
to address both secondary prevention and symptom management. The upshot of this massive, long-term
effort is that people with CVD are living longer and the incidence of death from this disease has substantially
decreased.92
We could stop there and declare victory, but that would be tragically shortsighted. Although we have reduced
the mortality associated with many serious chronic diseases, the prevalence of, for example, cancer, diabetes,
asthma, and heart disease—and the conditions that precede and perpetuate them—has grown, rather than
diminished. Rising disease prevalence is complex, of course, composed of at least three primary factors:
“…a rise in the population prevalence of disease, changes in clinical thresholds (and awareness) for treating
and diagnosing disease, and new technologies that allow physicians to treat additional patients with a
particular medical condition. A rise in total disease prevalence (both diagnosed and undiagnosed) is associated
with changing population risk factors such as obesity. For instance, among adults ages 20–74, obesity
prevalence increased from 14.5% (1976–1980) to 30.4% 20 years later (1999–2000). During the same period,
total diabetes prevalence, which is clinically linked to obesity, increased 53%, and diagnosed (treated) diabetes
prevalence increased 43%.”93
iiiIn the last century, overall life expectancy has risen from 51 to 79.4 years for women and from 48 to 73.9 years for men. Source:
Chapter on Human Health, EPA Report on the Environment, 2003.
Available at http://www.epa.gov/roe/roe/html/roeHealthSt.htm.
iv“According to the NCHS, if all forms of major CVD were eliminated, life expectancy would rise by almost seven years. If all
forms of cancer were eliminated, the gain would be three years.” Heart Disease and Stroke Statistics—2008 Update, American
Heart Association. Cited source: U.S. Decennial Life Tables for 1989-91, Volume 1, No. 4. Eliminating Certain Causes of
Death, 1989-91. NCHS, September 1999.
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The Role of Obesity in
Chronic Disease
Focusing on the role of obesity in
chronic disease could pay untold
dividends. “[O]ne of the most heritable
of human traits,”94 obesity is also
profoundly inuenced by lifestyle and
environment.95 It fuels (and can be
exacerbated by) chronic diseases with
high morbidity as well as mortality—
cancer, diabetes (now projected to
touch 30-40% of all Americans during
their lifetimes), heart disease, and
depression. As an outcome of the rise
in diabetes and other obesity-driven
diseases, Olshansky et al. made the
shocking projection in 2005 that “…
the steady rise in life expectancy during
the past two centuries may soon come
to an end.”96 In other words, if current
trends continue unchecked, future
generations will have shorter and less
healthy lives than the adults of today.
The urgency of this situation is
underscored in many compelling—
and poignant—scientic papers that
highlight some of the profound effects
of the obesity epidemic on all age
groups:
»Elderly: “Obese seventy-year-
olds will live about as long as those
of normal weight but will spend
more than $39,000 more on health
care. Moreover, they will enjoy
fewer disability-free life years and
experience higher rates of diabetes,
hypertension, and heart disease.”97
»Adults: “Two-thirds of adults in
the United States today are obese or
overweight.”98 “…the prevalence of
diagnosed type 2 diabetes mellitus
continued to increase concurrently
with increases in obesity.”99
The current (and growing) dominance of chronic and
degenerative diseases in the population is accompanied by
many grave problems in addition to shortened life expectancy
for today’s children: increasing disability over time, lowered
quality of life, and far greater costs—both for direct treatment
and as a result of important factors such as lowered productivity,
reduced income due to early disability, and the cost of supporting
disabled people in society for many years. As discussed above, the
cost of simply treating—with all the tools and expertise at our
command—the current epidemic of chronic disease threatens
to either bankrupt us or to displace resources needed for other
urgent priorities such as education, infrastructure, social security,
defense, research, and countless other vital activities.
We also know with greater certainty that longer life without
vitality and health imposes a considerable burden in addition to
the costs of treatment:
Depression is strongly associated with chronic
disease; it has become one of the world’s most
common conditions and results in severely decreased
quality of life and increased direct and indirect
costs.105
Overall health-related quality of life (HRQOL) has
gone down as chronic disease rates have risen. The
Mortality and Morbidity Weekly Report Surveillance
Summaries reported that “during 1993-2001, the
mean number of physically unhealthy days, mentally
unhealthy days, overall unhealthy days, and activity
limitation days was higher after 1997 than before
1997. …Adults increasingly rated their health as fair
or poor and decreasingly rated it as excellent or very
good.”106
Prolonged stress is exerted on families that provide
care for disabled elders. “An estimated 16 million
Americans—more people than live in all of New
England—nd themselves ‘sandwiched’ between
two generations, struggling to raise their kids while
caring for an aging loved one. That number is about
to explode: In 25 years, there will be 60 million
Americans between the ages of 66 and 84, many of
them needing full- or part-time care.”107
21st Century Medicine | 19
»Adolescents: “…extrapolation
from current data suggests that
adolescent overweight will increase
rates of CHD among future young
and middle-aged adults, resulting in
substantial morbidity and mortality
… more than 100,000 excess
cases of CHD attributable to the
increased obesity.”100
»Children: Type 2 diabetes,
previously almost unheard of in
children, “…has become common
among the pediatric age population,
accounting for ~40% of all diabetes
diagnosed.”101
A (highly simplied) model of the
multiple, complex inuences that create
obesity and associated chronic diseases:
If we concentrate our resources
at the bottom of the diagram, on
pharmacogenomics, we have already
lost the battle; chronic disease is already
entrenched and the costs of treating it
will only rise.
Environment / Lifestyle
Energy imbalance
Excess calories
Sedentary lives
Little/no exercise
Inefficient metabolism
Low energy
Psychosocial
Stress
Sleep deficit
Loneliness
Diet/Nutrition
High-fat, high-sugar foods
High fructose corn syrup
Empty calories
Low fiber
Environment
Hormonal changes
Respiratory diseases
Depression
Pharmacogenomics Nutrigenomics / Primary Prevention
Obesity
inflammation
Hypertension Arthritis
Diabetes Heart Disease
Creativity and innovation are lost to
underemployment or unemployment and the
shrinking work force must support an increasingly
disabled aging population for many more years.
We can and should feel grateful that the threat of acute
disease decreased so substantially over the last century and,
concomitantly, that our life expectancy increased dramatically.
We must also recognize, however, the urgent need to redirect
some of our healthcare dollars, energy, expertise, and time
toward stopping and ultimately reversing the spread of
chronic disease. While it is certainly true that we all must
die of something, and conquering acute disease made space
for chronic diseases to rise to the top of the mortality charts,
we cannot allow our much longer lives to be increasingly
haunted by unprecedented rates of chronic disease and its
accompanying disability, depression, and sharply rising costs.
Instead of spending all our resources on managing symptoms
and secondary prevention, we must turn our attention to
causal factors. We know with steadily increasing condence
and knowledge that the primary driver of chronic disease is the
interaction among genes, activities of daily living (lifestyle), and
the environment. Describing a model that folds that very general
awareness into actual clinical practice, enabling physicians to
acquire effective skills and tools for addressing the unique pattern
of each individual patient’s life and health, is the ultimate goal of
this paper.
the chAnging
medicAl enVirOnment
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20 | 21st Century Medicine
The Role of Obesity in Chronic
Disease, continued
It is important to note, however,
that there is no precise, predictive
formula. One person’s obesity is
not identical in cause, signs and
symptoms, or secondary outcomes to
another’s, and thus both treatment and
prevention must be individualized to
accommodate the genetics, lifestyle,
and environment of each patient.
Any model for managing chronic
disease that does not address all of
these components will fall short in
comprehensiveness and effectiveness.
In a 2008 publication in Circulation,102
the American Heart Association
described a comprehensive population-
based approach to preventing obesity,
including the following key strategies
(among others):
»Prevention at the population level,
with emphasis on key risk subgroups
»Differentiating environmental and
policy approaches from clinically-
based interventions
»Use of an ecological model that
“includes multiple layers of
inuences on eating and physical
activity across multiple societal
sectors”
Often in medicine the marshaling of
substantial and focused resources to
ght a public health problem waits
upon the research agenda. While
there are many questions yet to be
answered about how and why obesity
develops and how and why it is such
a risk factor for other serious diseases,
it is a long and expensive process to
test and verify strategies for prevention
and treatment.103 We cannot afford
Improving the Response to Chronic Disease
Chronic disease is now the principal cause of disability and use of health
services and consumes 78% of health expenditures. (p. 1057 in the
publication cited) [D]eveloping a different way to practice medicine for
chronic disease is at the heart of any solution to the problem.
(p. 2975, a reply to letters generated by the cited publication)
—halStead holman, md, Jama, 2004108
The burden of harm conveyed by the collective impact of all of our health
care quality problems is staggering. It requires the urgent attention of all the
stakeholders: the health care professions, health care policymakers, consumer
advocates and purchasers of care. The challenge is to bring the full potential
benet of effective health care to all Americans while avoiding unneeded and
harmful interventions and eliminating preventable complications of care.
Meeting this challenge demands a readiness to think in radically new ways
about how to deliver health care services and how to assess and improve their
quality. Our present efforts resemble a team of engineers trying to break the
sound barrier by tinkering with a Model T Ford. We need a new vehicle or
perhaps, many new vehicles. The only unacceptable alternative
is not to change.
—maRK chaSSin, md, mph; iom national RoundtaBle on
health caRe Quality, Jama, 1998109
The three arenas in which fundamental change is required in
order to improve both prevention and treatment of chronic
disease are medical education, clinical care (which is conditioned
by medical education), and consumer/patient behavior. This
paper focuses primarily on clinical care.
Medical education
The Institute of Medicine report, Crossing the Quality Chasm, in the
chapter on “Preparing the Workforce” (p. 213) observes: “Despite
changes that have been made, the fundamental approach to
medical education has not changed since 1910.”110 The report
also addresses some of the factors that make changing medical
education very difcult. However, it does not directly address
the imperative to integrate creative and innovative approaches
to chronic disease into the process. Medical education must
teach physicians to quickly and skillfully differentiate situations
requiring an acute-care intervention from those presenting the
very different challenge of complex, chronic disease. Once that
the chAnging
medicAl enVirOnment
21st Century Medicine | 21
that delay; there are far too many
lives at stake. Dr. Richard Horton,
editor-in-chief of The Lancet, addressed
this issue in an editorial titled, “The
Precautionary Principle”:
We must act on facts, and on the most accurate
interpretation of them, using the best scientic
information. That does not mean we must
sit back until we have 100% evidence about
everything. Where the state of the health of
the people is at stake, the risks can be so high
and the cost of corrective action so great, that
prevention is better than cure. We must analyze
the possible benets and cost of action and
inaction. Where there are signicant risks
of damage to the public health, we should
be prepared to take action to diminish those
risks even when the scientic knowledge is not
conclusive, if the balance of likely costs and
benets justies it.104
We must act in concert with emerging
research, being willing and able to
adapt as new information becomes
available. That is why we need a model
of care that is comprehensive, yet
exible; science-based but not rigidly
bound to an imperfect and incomplete
evidence base; personalized and
holistic. That model will be presented
and discussed in Chapters 4 and 5.
differentiation is achieved, then physicians must be given new
tools, information, and skills with which to address the common
comorbidities and complexities of chronic disease. Key concepts
that underlie and will facilitate these fundamental changes are
presented in Chapters 4 and 5 of this paper.
Clinical care
Changes in the roles of both patients and clinicians are critical
to transforming our healthcare system. Chapter 4 addresses
“The Clinician’s Dilemma”: how to practice in such a way that
both the continuing advances of science and the essential art
of medicine are integrated seamlessly into clinical practice,
neither overshadowing the other. Clinicians must improve
their capacity to incorporate important emerging evidence
into a personalized, systems-oriented model of care, within the
context of a strong healing partnership with patients. Chapter
5 presents the functional medicine model and methods that
facilitate this evolution as well as an approach to establishing and
strengthening the healing relationship. Two cases that exemplify
the process are presented.
Consumer (Patient) needs and preferences
The growth and sustained energy of consumer interest in
alternative and complementary medicine over the last quarter
century is one indicator of the desire patients have for a different
kind of healthcare system. Although not addressed directly
in this paper, healthcare consumers must be assisted to take a
lifelong interest in the forces that push each of us toward health
or disease. As difcult as it is for physicians and other health
practitioners to alter their mode of practice, that’s how difcult
it is for patients to alter their mode of living to maximize the
prospects of health and minimize the risks of disease. These
changes represent a major undertaking and we will not be
successful unless both consumers and providers of health care
commit to a long-term, sustained effort.
22 | 21st Century Medicine
21st Century Medicine | 23
21st
century
medicine:
A New Model for Medical
Education and Practice
Chapter 3
________________________________________
Emerging Models
Personalized Medicine
If it were not for the great variability among individuals,
medicine might as well be a science, not an art.
—SiR William oSleR, 1892
What is it?
Personalized medicine can be described as the effort to dene and strengthen
the art of individualizing health care by integrating the interpretation of patient
data (medical history, family history, signs, and symptoms) with emerging “–omic”
technologies—nutritional genomicsv
, pharmacogenomicsvi, proteomicsvii, and
metabolomicsviii.111 Developing these strategies is critical to enabling physicians
to match individual patients to the best diet, environment, nutraceuticals, and
pharmaceuticals for their genetic make-up—a process that will eventually
v“Nutritional genomics or, as commonly used, nutrigenomics: The study of how different
foods may interact with specic genes to increase the risk of common chronic diseases such as
type 2 diabetes, obesity, heart disease, stroke and certain cancers. Nutrigenomics also seeks to
provide a molecular understanding of how common chemicals in the diet affect health by altering
the expression of genes and the structure of an individual’s genome. The premise underlying
nutrigenomics is that the inuence of diet on health depends on an individual’s genetic makeup.
(From MedicineNet.com)
vi“…pharmacogenomics includes identifying candidate genes and polymorphisms, correlation
of polymorphisms with therapies, prediction of drug response and clinical outcomes, reduction in
adverse events, and selection and dosing of drugs based on genotype.” (Issa, 2007)
vii“Proteomics: The study of the proteome, the complete set of proteins produced by a species,
using the technologies of large-scale protein separation and identication. The term proteomics
was coined in 1994 by Marc Wilkins who dened it as “the study of proteins, how they’re modied,
when and where they’re expressed, how they’re involved in metabolic pathways and how they
interact with one another.” (From MedicineNet.com)
viii“Metabolomics/Metabonomics: The study of metabolic responses to drugs, environmental
changes and diseases. Metabonomics is an extension of genomics (concerned with DNA) and
proteomics (concerned with proteins). Following on the heels of genomics and proteomics,
metabonomics may lead to more efcient drug discovery and individualized patient treatment with
drugs, among other things. (From MedicineNet.com)
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24 | 21st Century Medicine
Integrating
Pharmacogenomic Testing
in Clinical Practice
McKinnon et al.115 describe a
general process for developing
pharmacogenomics tests that can be
used in clinical practice. Each of these
steps represents a point at which poor
outcomes may completely stall the
development of an affordable and
effective clinical test:
1. Identify circumstances in which
knowledge of inter-individual
variation in drug response is likely
to improve clinical (or nancial
outcomes)
2. Find a signicant genotype-
phenotype association
3. Determine reproducibility across
ethnic populations
4. Propose model of how genotyping
would guide clinical practice
5. Collect data on cost effectiveness of
new pharmacogenomic prole vs.
current practice
6. Educate stakeholders on
appropriate use
7. Implement testing in a staged
manner
revolutionize medicine. Such a comprehensive individual
ngerprint is still many years away from being feasible, in
research or clinical practice. It is not too early, however, to begin
learning about it and applying key concepts and early data to
patient care in incremental steps as the evidence base advances.
To date, the research underlying personalized medicine has
concentrated mostly on pharmacogenomics. The knowledge
that “a relatively large number of patients treated for cancer,
infectious disease, psychiatric illnesses, respiratory diseases
and cardiovascular conditions are not responding to the drugs
they are given”112 has been one of the key drivers of the eld.
The process of developing new drugs specically designed for
personalized applications involves many phases: identication
and screening of candidate genes; detection and description
of various polymorphisms that affect drug response (e.g., slow
or rapid metabolizers); the correlation of each polymorphism
with possible therapeutic targets; and the evaluation of clinical
outcomes with large enough study sizes to create condence in
the efcacy of the new strategy. All of these steps must occur
before selection of a drug and specication of therapeutic dosage
can be based on genotype.113 Once the drug development process
is complete, the transformation of research-based data into a new
tool for clinical practice must await a cost-effective screening test
for patients (a process that involves many challenging and time-
consuming phases—see Sidebar), delineation of which patients
should be screened and at what stage in their care, and long-
term follow-up to check for possible adverse effects of therapy.
The identication of drugs already in the pharmacopeia that
have inter-individual variability in dosing, efcacy, and/or side
effects that would make them amenable to a pharmacogenomics
approach will also be a lengthy and expensive process, as there
are thousands of drugs that could be tested for such personalized
applications. Screening tests to detect various polymorphisms
must also be developed and they must be cost effective if they
are to be utilized routinely in clinical care. Pharmacodiagnostic
tests that enable clinicians to quickly and cost effectively identify
patients who are at risk for adverse drug responses “must possess
high sensitivity and specicity with regards to their predictive
performance.”114
A couple of examples will indicate the incalculable potential—
and the complexity and costliness—of pharmacogenomics as a
clinical strategy:
emerging mOdels
21st Century Medicine | 25
New drug development: Herceptin® (trastuzumab) is a monoclonal antibody developed
to treat breast cancer that over-expresses HER2 (human epidermal growth factor receptor
2). This characteristic “is associated with an aggressive phenotype, high recurrence rate
and reduced survival”116 and it affects approximately 25-30% of breast cancer patients.117
Before a drug could even be conceptualized, the HER2 protein had to be detected and
reliably identied, and many breast cancers had to be analyzed to discover the proportion
with overexpressed HER2. Then, the search for a drug targeted to this trait could begin.
Ultimately, trastuzumab was developed, tested, and validated in research trials as an
effective treatment for breast cancers that over-express HER2; its ability to work with other
chemotherapeutic agents was also assessed. Two cost-effective screening tests were developed
and are now available—immunohistochemistry (IHC—appropriate as a general screening
tool for all breast cancer) and uorescence in situ hybridization (FISH—used as further
screening for patients with 2+ and 3+ IHC scores).118 And “…ve recent adjuvant breast
cancer trials have demonstrated an astonishing and highly reproducible benet in halving the
recurrence rate and reducing mortality in patients with this phenotype.”119
Existing drug specications: Warfarin, an effective anticoagulant in use for many
decades, has “a narrow therapeutic range because of both genetic and environmental
factors,”120 and has been under-prescribed because of “historically high rates of drug-
associated adverse events.”121 Understanding these factors sufciently well to alter dosing
appropriately would enable this cost-effective drug to be used more widely. Studies assessing
the role of patient demographics and known variants in CYP2C9 alleles and VKORC1
genotypes have been performed, and therapeutic response to warfarin is now known to
vary among Jewish (both Ashkenazi and Sephardic origins), African American, and Asian
patients.122, 123, 124 In 2005, “the U.S. FDA Clinical Pharmacology Sub-Committee (CPSC)
of the Advisory Committee for Pharmaceutical Science voted to re-label the dosing of
warfarin to take into consideration the new information.”125 It is not known how many
patients already on warfarin have undergone testing to re-evaluate their dosage since the
prescribing recommendations were changed. However, at least one study has determined
that “prospective application of a multivariate CYP2C9 gene-based warfarin dosing model
is feasible,”126 and another reported that “a quantitative dosing algorithm incorporating
genotypes for 2C9 and VKORC1 could substantially improve initial warfarin dose-selection
and reduce related complications.”127
The incorporation of nutrigenomics (the effect of diet on gene expression), nutrigenetics (effect of genetics
on response to diet, foods, or nutrients), proteomics, and metabolomics into the personalized medicine
model has moved much more slowly,128, 129 perhaps simply as a reection of the marked dominance of
drug treatments that characterizes our healthcare system and shapes the funding priorities (see Sidebar in
Chapter 2). However, much that is learned in pharmacogenomics will drive the knowledge base in these
related elds as well because the underlying principle is common to all: individual genetic variations affect
our physiological and biochemical response to virtually everything we are exposed to. This represents a
fundamental alteration in our understanding of health and disease. The knowledge of how to identify and
manage these individual differences is acutely needed for lifelong prevention of chronic disease. It won’t
be enough to say “Eat more vegetables and less fat and sugar.” We will need to be able to individualize
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26 | 21st Century Medicine
healthy diets, add targeted nutraceuticals, prescribe specic exercise programs, advise stress reduction
efforts, plan to avoid certain pollutants, all based on individual genetic variations. Ultimately, personalized
medicine will not be fully realized until all the inuences, effects, and interactions are researched and
described in such a way that practitioners are able to bring them to bear on an individual patient’s health
and on lifelong prevention of chronic disease.
Strengths and weaknesses
The ultimate promise of personalized medicine is its potential to uncover “the causes of the causes”
of disease.130 From the unlocking of the human genome to the development of proteomics (wherein
we begin to understand how the proteins made by genes behave131), scientists can now demonstrate
how individualized both health and disease really are. It’s a powerful and exciting model that is already
beginning to affect both research and clinical practice. Its strength is the rapidly developing science (all
the –omics) that opens new vistas and new possibilities for dramatically increasing the effectiveness of
individualized prevention and treatment strategies.
On the other hand, the many challenges of transferring this model to clinical practice are daunting; they
include:
The “clinical complexity of genomic-based diagnostics and treatment.”132 A recent NIH
report phrases the complexity question clearly: “An enormous scientic challenge now
presents itself: What are the best ways to understand, prevent, and treat common, chronic
diseases like heart disease, cancer, addiction, and mental illness when it is apparent that they
are the result of interactions between individuals—in all their biological complexity—and
their ever-changing physical, behavioral, and societal environments?”133
Excessive cost134
Regulatory issues135, 136
Ethical concerns137
The need for new information technology138
At the level of patient care, additional complex challenges arise that may take decades to resolve:
Devising accurate and cost-effective genomic and/or proteomic screening tools
Identifying biomarkers that will indicate whether/when an active adverse process is in play for
specic conditions in a given patient
Testing and validating diagnostic tools across many populations
Selecting appropriate patients for screening and demonstrating the usefulness of screening in
improving patient outcomes through long-term clinical trials
Convincing third-party payers to reimburse for screening tests (likely to happen only when the
results from long-term trials demonstrate cost-effectiveness)
Interpreting individual patient screening reports appropriately
21st Century Medicine | 27
Devising and validating effective interventions based on individual screening results
Common ground with other emerging models
As shown in Figure 2 (Chapter 1), personalized medicine shares many features with other emerging
models: the emphasis on discovering individual patients’ genetic vulnerabilities, the vision of
individualized diagnostics and treatment, and the reliance on a powerful (and still emerging) scientic
evidence base. It also shares with other models the absence of a clear and practical method of
integrating emerging information into medical education and practice. Nor does it address structural
and multidisciplinary issues in clinical practice that are part of the chronic-care model and integrative
medicine.
Role in a synthesized, comprehensive model of 21st century medicine
Despite the rapidly evolving research base, therefore, personalized medicine does not (yet) have a robust,
consistent architecture for clinical applications, nor does it describe a clear pathway toward achieving that
goal. Research designs are still in development, and research ndings do not specify how personalized
medicine may (or may not) contribute to a new model of care for chronic disease. Even when a gene
mutation, or SNP, can be identied, we may still be “six degrees of separation removed from the
functional aspects of the disease,”139 because gene analysis does not tell us which protein and protein
pathways are affected and what the aberrant protein is doing. “Proteins are actually the drug targets;
analysis of genes and gene expression just gives an indication of whether or not the proteins may be
present.”140 The same can be said of the effects of diet, environmental toxins, psychosocial inuences, and
many other lifestyle and environmental factors on gene expression and protein function. For these reasons,
it is difcult to plan for the integration of this model into medical education in a systematic way in the
near future.
It will be necessary, therefore, to ensure that whatever transformative model is used, it will allow clinicians
to integrate new and useful information from personalized medicine as and when it becomes available,
and will also empower them to respond effectively now to the urgent need for improved prevention and
management of complex, chronic disease. Perhaps the single most valuable portion of the personalized
medicine model at the moment is the transparency it brings to the concept of patient individuality. The
evidence clearly reveals that each patient is a unique individual—one whose gene expression patterns are
constantly in ux and whose complex and ever-changing response to treatment, environment, and lifestyle
will challenge physicians to listen differently, see differently, and respond differently than taught by the
linear model of acute care.
emerging mOdels
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28 | 21st Century Medicine
Prospective Medicine
“The ability to identify those individuals most at risk for developing chronic diseases and to provide a customized means to prevent
or slow that progression are emerging competencies and provide the foundation for prospective care.”
—Ralph SnydeRman, md and R. SandeRS WilliamS, md 141
What is it?
A relatively new concept introduced in 2003, prospective medicine is a descriptive rather than a prescriptive
term, encompassing “personalized, predictive, preventive, and participatory medicine.”142 Snyderman argues
persuasively that a comprehensive system of care would address not only new technologies (e.g., identication
of biomarkers, use of electronic and personalized health records), but also delivery systems, reimbursement
mechanisms, and the needs of a variety of stakeholders (government, consumers, employers, insurers, and
academic medicine). Prospective medicine does not claim to stake out new scientic or clinical territory;
instead, it focuses on creating an innovative synthesis of technologies and models—particularly personalized
medicine (the “-omics”) and systems biology—in order to “determine the risk for individuals to develop
specic diseases, detect the disease’s earliest onset, and prevent or intervene early enough to provide maximum
benet. Each individual would have a personalized health plan to accomplish this.”143
Strengths and weaknesses
A very compelling element of prospective medicine is the call for fundamental change in clinical practice—
from treating people only when they are sick enough to visit the doctor’s ofce to prospectively examining
individual risks and developing comprehensive preventive strategies based on the best available evidence at
the time. This would, indeed, revolutionize medicine; not only would it shift the focus of primary care, but
it would establish a serious partnership between patient and clinician aimed at lifelong health. Snyderman
emphasizes the need for clinical medicine and the emerging genomic models to integrate their respective
knowledge and skills to create the best outcomes for patients. He discusses some diagnostic and risk-assessment
tools that are already available, such as the following examples:
Know Your Number®, a program that “uses … synthesis modeling to quantify an individual’s risk
of developing chronic, preventable, obesity-related diseases such as diabetes, chronic obstructive
pulmonary disease, and heart disease. In addition, KYN calculates what modiable factors are
contributing to that risk so that individuals can take steps to improve their overall risk prole.”144
Although Know Your Number is not available directly to consumers, other similar programs are.
One example is Navigenics Health Compass,145 offering “A scan of your whole genome, carried
out by a government-certied laboratory, that captures data on 1.8 million of your genetic risk
markers.” For $2500, individuals can obtain an analysis of their “genetic predisposition for a
variety of common health conditions, and the information, support and guidance to know what
steps you can take to prevent, detect or diagnose them early.” For $250 per year, they will have a
subscription that entitles them to regular updates.
Biomarkers can be assessed through an analysis of 250 serum proteins ($3400). According to the
company’s Web site: “Biophysical250 … measures 250 different biomarkers that may indicate
the presence of diseases and conditions often before symptoms appear. Unlike standard physicals
21st Century Medicine | 29
that measure only up to 40 biomarkers, Biophysical250 simultaneously assesses hundreds of
biomarkers used by 12 different medical specialties.”146
Two gene-expression assays that predict recurrence of breast cancer in patients with stage I or
II node-negative breast cancer. These tests can be used to individualize follow-up treatment by
helping to determine “the need for systemic adjuvant therapy in such patients.”147
Also compelling is the call to involve a broad range of stakeholders to “work together to develop
innovative applications of new technologies and appropriate delivery models.”148 It is certainly true that
reimbursement strategies and academic training practices will have to evolve to encompass such a broad-
based new model of care, and retraining existing practitioners must become a high priority.
What’s missing? Like the other emerging models we are discussing, prospective medicine does not provide
a clear road map for integrating these new technologies into clinical practice. Precisely how, one wonders,
will the 500,000+ MDs and DOs already in practice be retrained? How will academic medicine evolve?
How many patients can spend $2500-$3500 on laboratory tests to assess risk biomarkers? How much
new and expensive testing is actually necessary compared to how much risk is already clear when a
comprehensive history is taken and a thorough examination including (mostly) standard laboratory tests is
performed? And what, exactly, will change in clinical practice once expanded information is in hand from
these new technologies? Will doctors still be in the same position they are in today—suggesting better diet,
losing weight, and reducing stress without knowing how to help their patients make all of that happen?
The big missing piece in prospective medicine (at least as described thus far in the literature) lies in the
absence of a clear, practical, and systematic method for altering clinical practice. Recognizing that the
interactions between doctor and patient and between patients and their lifestyle-environment exposures
and choices are where real change happens, Johns and Brigham,149 offer this commentary on a post-
prospective medicine world:
This “next next transformation” will identify “healthy” biologic processes (i.e., homeostatic) and provide tools for measuring
early deviations from health (“unhealth”) that are not necessarily disease specic but that predict dire outcomes and warrant
health-focused interventions. For example, many chronic diseases (diabetes, atherosclerosis, autoimmune diseases) share
inammation as a common mechanism. Characterizing an individual inammatory phenotype may be a potent health
predictor. And inammatory responses to stress can be modied by behavior. Such health-focused treatment is the logical step
beyond the “next transformation” that Snyderman and Yoediono advocate.
Common ground with other emerging models
Prospective medicine urges the integration of the developing sciences of personalized medicine and
systems biology with the skills and knowledge of clinicians, and describes recommendations for revisions
in reimbursement mechanisms and medical education that will be required in order to implement
a comprehensive new system of care. It clearly relies on the emerging evidence base, but not to the
exclusion of other important information. It does not specically address the chronic-care model, nor
issues of integrated care or integrative medicine; neither diagnostic approaches nor treatment strategies
appear to include a multidisciplinary model of care.
emerging mOdels
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30 | 21st Century Medicine
Crossing the Quality
Chasm
The Institute of Medicine’s report,
Crossing the Quality Chasm,151 comments
extensively on the unmet needs of
those with chronic conditions:
»Page 4: “… there remains a
dearth of clinical programs with
the infrastructure required to
provide the full complement of
services needed by people with
heart disease, diabetes, asthma, and
other common chronic conditions
(Wagner et al., 1996). The fact that
more than 40% of people with
chronic conditions have more than
one such condition argues strongly
for more sophisticated mechanisms
to communicate and coordinate
care (The Robert Wood Johnson
Foundation, 1996).”
»Page 9: “Care for the chronically
ill needs to be a collaborative,
multidisciplinary process.”
»Page 28: “In a population
increasingly aficted by chronic
conditions, the health care delivery
system is poorly organized to provide
care to those with such conditions.”
»Page 29: “Thus the American
health care system does not have
well-organized programs to provide
the full complement of services
needed by people with such chronic
conditions as heart disease, cancer,
diabetes, and asthma.”
»Page 89: “Common chronic
conditions should serve as a starting
point for the restructuring of health
care delivery because, as noted in
Chapter 1, chronic conditions are
Role in a synthesized, comprehensive model of 21st
century medicine
Because prospective medicine relies on personalized medicine
and systems biology for the science of risk-assessment, many of
its strengths and its limitations are found in those two models.
It is, however, more comprehensive in sweep than either of
them, incorporating not only technologies such as electronic
health records but also acknowledging the need for simultaneous
reform of the reimbursement structure and the training of future
physicians. Thus, it is an important step forward, but it still lacks
a robust, consistent architecture for clinical applications.
Chronic-Care Model
What is it?
The chronic-care model (CCM) is briey outlined in Chapter 1
and fairly thoroughly described in the Appendix, where extensive
material from the Improving Chronic Care Web site is included.
The primary focus of this model is to include “…the essential
elements of a healthcare system that encourage high-quality
chronic disease care…. the community, the health system, self-
management support, delivery system design, decision support
and clinical information systems. Evidence-based change
concepts under each element, in combination, foster productive
interactions between informed patients who take an active part
in their care and providers with resources and expertise.”150
The CCM is a response to powerful evidence that patients with
chronic conditions often do not obtain the care they need, and
that the healthcare system is not currently structured to facilitate
such care (see Sidebar).
Strengths and weaknesses
The chronic-care model has the advantage of having been
around for more than a decade; it has undergone considerable
testing and revision. Implementation trials have indicated that,
when enough of the model can be implemented, compliance
with current algorithms and guidelines can be improved for
conditions such as diabetes,152, 153 depression,154 and tobacco
cessation.155 The CCM is a structure-of-care (or process-
of-care) more than a content-of-care model; it describes a
21st Century Medicine | 31
now the leading cause of illness,
disability, and death in the United
States, affecting almost half of the
population and accounting for the
majority of health care resources
used (Hoffman et al., 1996).”
»Page 94: “Four chronic conditions
(cardiovascular disease, cancer,
chronic obstructive pulmonary
disease, and diabetes) account for
almost three-quarters of all deaths
in the United States (Centers for
Disease Control and Prevention,
1999).”
»Page 211: “The ability to plan
care and practice effectively using
multidisciplinary teams takes
on increasing importance as the
proportion of the population with
chronic conditions grows, requiring
the provision of a mix of services
over time and across settings….
A changing relationship between
clinicians and their patients also calls
for new skills in communication and
support for patient self-management,
especially for patients with
chronic conditions. Collaborative
management requires collaboration
between clinicians and patients in
dening problems, setting goals, and
planning care; training and support
in self-management; and continuous
follow-up (Von Korff et al., 1997).
Patients with chronic conditions who
are provided with knowledge and
skills for self-management have been
shown to experience improvements
in health status and reduced
hospitalizations (Lorig et al., 1999).
Clinicians need to have skills to train
multidisciplinary, multi-stakeholder approach to delivering care
that will improve both patient and practitioner compliance with
current evidence-based best practices. For this reason, integrating
new technologies, such as those emerging from personalized
medicine, are not explicitly addressed; one might assume that as
those tools make their way into clinical guidelines and algorithms,
they will become part of the CCM as well. However important
improving the structure of care may be—and we certainly
agree that it is important—the care thus provided will still be
limited to the current medical model, which does not address
individualizing care, lifelong primary prevention, or reversal of
chronic disease, and which is primarily pharmaceutical in nature.
We could imagine implementing, for example, personalized
medicine using the chronic-care model, but no mechanism for
achieving that is described. In fact, just implementing the full
CCM itself is a very difcult proposition that encounters many
barriers (e.g., no consensus on the value of the changes, limited
change management skills within organizations, too many
competing priorities, and failure to engage the commitment
of physicians).156 The Academic Chronic Care Collaborative,
representing 22 academic medical centers, has reported
some initial promising outcomes from their experiences with
implementing aspects of the CCM.157 It is worth noting that these
institutions were committed to providing effective leadership and
resources for the change process. The Agency for Healthcare
Research and Quality provides an extensive Toolkit for Implementing
the Chronic Care Model in an Academic Environment.158
Common ground with other emerging models
The CCM shares with integrative medicine an emphasis on a
multidisciplinary care model, the use of evidence-based best
practices, and engagement of the patient in self-care. It does not
address biochemical and physiological individuality, any of the
emerging genomic technologies, or the inuence of underlying
mechanisms of disease. It shares with prospective health care a
focus on structural, system-wide change, although the two models
emphasize different aspects of structural change.
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patients in techniques of good self-
management.”
»Page 237: “Patients with chronic
conditions, for which certain routine
examinations and tests are crucial in
order to prevent complications, do
not all get the care they need.”
Note: Citations included in the above
quotations are available in the Institute
of Medicine report, but are not
provided here.
Crossing the Quality Chasm,
continued
Role in a synthesized, comprehensive model of 21st
century medicine
The CCM advances our knowledge of how to improve the
structure or process of care for chronic disease using standard
approaches, but it does not advance our ability to select more
effective strategies for actually improving both treatment and
prevention. Still lacking is a robust, consistent architecture for
selecting the most effective clinical applications for each unique
patient.
Evidence-based Medicine (EBM)
What is it?
EBM is a tool for improving clinical practice. Its stated goal
is to ensure that clinical decision making is grounded in the
best available evidence. Despite its many limitations, it wields
a great deal of power over medical training, clinical practice,
and—increasingly—reimbursement decisions and legal
determinations.159, 160 We include it in our discussion of emerging
models because of its multifaceted inuences on patient care.
Although it is beyond the scope of this paper to explore EBM
in depth, it is critical to the future of health care to understand
its strengths and weaknesses. To that end, we provide a brief
description of this evolving paradigm.
Since the late 1970s, various efforts have been made to
systematize the use of research ndings in clinical decision
making.161 Rather than expecting each practitioner to establish
and maintain a constant surveillance over a rapidly expanding
evidence base, and to know which studies should generate
the highest level of condence, specic guidelines have been
proposed concerning the interpretation of evidence that
inuences clinical decision making. There have been many
denitions and ratings of what constitutes poor, good, and
best evidence, but in the early 1990s, the term evidence-based
medicine appeared for the rst time,162, 163 reecting an increasing
consensus that a more standardized approach to the use of
medical evidence was on the way. Early efforts sought explicitly to
reduce “…the emphasis on unsystematic clinical experience and
pathophysiological rationale” while promoting “the examination
of evidence from clinical research.”164
21st Century Medicine | 33
A hierarchy of evidence reliability was proposed, with meta-analyses and systematic reviews at the top and
personal communications at the bottom (see Figure 6). Over the years, this hierarchy has been revised and
adapted many times for a number of reasons:
It did not identify a mechanism for decreasing or increasing an assessment of value based
upon, for example, study size, adequacy of blinding, bias, directness of the evidence, and
other factors.165
It failed to accommodate many important criteria for translating evidence into clinical
practice—for example, the degree to which outcomes being tested were important to patients,
whether results were consistent with past studies, and whether condence intervals were overly
broad.166
It inappropriately identied systematic reviews and meta-analyses as evidence (they are,
rather, interpretations of the evidence and should be produced, at least in part, based on
EBM principles).167, 168
It did not differentiate between quality of evidence and strength of recommendations.
“High quality evidence doesn’t necessarily imply strong recommendations, and strong
recommendations can arise from low quality evidence.”169
One example of a subsequent adaptation is provided in Figure 7, where we can see that other useful
criteria were added to the model, altering the earlier and more simplistic assessment of evidence
usefulness.170
The basic concepts have continued to evolve. “In 2000, the Evidence-Based Medicine Working Group
presented the second fundamental principle of EBM (the hierarchy of evidence being the rst): Whatever
the evidence, value and preference judgments are implicit in every clinical decision. A key implication of
this second principle is that clinical decisions, recommendations, and practice guidelines must not only
attend to the best available evidence, but also to the values and preferences of the informed patient.”171
A major advance over the use of any hierarchy, however complex, has been the development of the
GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Figure 8
shows a partial representation of this system; in practice, it has other important elements as well. The
GRADE system describes a very sophisticated, multi-level evaluation of evidence; its purpose is to
strengthen recommendations for clinical practice and to increase condence in those recommendations.
Because of its complexity, however, it is not intended for use by individual clinicians, who generally
have neither the time nor the expertise to implement it. It is aimed primarily at researchers and clinical
guideline developers, who have not heretofore used a consistent and uniform methodology that is
transparent to all potential users.172 GRADE software is now available for free at the GRADE Working
Group’s Web site,173 making it even more likely that its use will continue to expand.
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34 | 21st Century Medicine
1. A Systematic reviews; meta - analyses
B RCTs
C Experimental designs
2. A Cohort control studies
B Case control studies
3. A Consensus conference
B Expert opinion
C Observational study
D Other types of study (e.g., interview -based)
E Quasi-experimental, qualitative design
4. Personal communication
Figure 6:
Hierarchy of Evidence (Sackett)
Effectiveness Appropriateness Feasibility
Excellent Systematic reviews
Multi-center studies
Systematic reviews
Multi-center studies
Systematic reviews
Multi-center studies
Good RCTs
Observational studies
RCTs
Observational studies
Interpretive studies
RCTs
Observational studies
Interpretive studies
Fair Uncontrolled trials; dramatic
results
Before and after studies
Non-randomized CTs
Descriptive studies
Focus groups
Descriptive studies
Action research
Before and after studies
Focus groups
Poor Descriptive studies
Case studies
Expert opinion
Studies with poor methodology
Expert opinion
Case studies
Studies with poor
methodology
Expert opinion
Case studies
Studies with poor
methodology
Figure 7:
Hierarchy of Evidence (Evans)
21st Century Medicine | 35
A. Criteria for Assigning Level of Evidence
Type of Evidence
Randomized trial High
Obsvervational study Low
Any other type of research evidence Very Low
Increase level if:
Strong association (+1)
Very strong association (+2)
Evidence of a dose-response gradient (+1)
Plausible confounders reduce observed effect (+1)
Decrease level if:
Serious or very serious limitations in quality (-1) or (-2)
Important inconsistency (-1)
Some or major uncertainty about directness (-1) or (-2)
Imprecise or sparse data* (-1)
High probability or reporting bias (-1)
B. Denitionsforlevelsof evidence
High Further research is not likely to change our condence in the effect
estimate
Moderate Further research is likely to have an important impact on our
conednece in the estimate of effect and may change the estimate
Low Further research is very likely to have an important impact on our
condence in the estimate of effect and is likelh to change the estimate
Very Low Any estimate of effect is uncertain
*Few outcome events or observations or wide condent limits around an effect
estimate
Figure 8:
Overview of the GRADE System for Evaluating Evidence (Bagshaw)
Over the years, a number of studies have veried that teaching EBM will, in fact, signicantly increase
the degree to which practitioners apply it.174 Training is more successful if it is both experiential and
didactic.175, 176, 177 Unfortunately, there are very few studies available as yet that tell us whether EBM
improves overall patient health over a period of years.
Strengths and weaknesses
There can be little doubt that a thoughtful evaluation of evidence is an indispensable factor in delivering
high-quality health care. The emergence of formal assessment processes reects a desire to establish
greater clarity and condence about the reliability of evidence. Even a casual user of Medline or PubMed
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quickly becomes aware of the overwhelming quantity of published research available today; it is a
daunting prospect to identify the best or most relevant papers among hundreds or thousands that may
be available on a particular topic. For example, a PubMed search for the phrase evidence-based medicine in
titles and abstracts returns nearly 5000 entries encompassing dozens of journals! There are, of course,
tools for narrowing a search term or process, but it is still inordinately time consuming to obtain, read,
evaluate, and then compare even a few individual research papers on a specic subject. Such a process,
even if an EBM hierarchy is used, is also subject to a great deal of individual bias. Thus, any tool that
provides signicant and reliable assistance in such an endeavor is welcome, and that is one of the primary
rationales for the development of clinical guidelines.ix
As the use of EBM has become increasingly widespread, its limitations and weaknesses have also become
more apparent. Paramount among the problems is that EBM reects an acute-care model: it most
often assumes that the goal of care is a single diagnosis followed by a hierarchy of (primarily) single-
agent treatments. Although GRADE has made an admirable attempt to compensate for many EBM
weaknesses, these fundamental goals remain the gold standard. Therefore, EBM fails at the same point
where the research itself fails—in its inability to account for unique patient geno/phenotypes, multiple
comorbidities, and personalized approaches to care that include multiple interventions for complex,
chronic disease. Such multifaceted interventions may include dietary, nutraceutical, pharmaceutical and/
or surgical recommendations, as well as many options from the natural medicine world (e.g., botanical
medicine, acupuncture and oriental medicine, body/mind practices).
EBM and any guidelines derived from applying an EBM model to the evidence are, of course, only as
good as the underlying research, which presents several problems:
Not only is the research agenda disproportionately driven by the pharmaceutical industry,
but it is tainted by the failure to publish negative or neutral results and by industry bias (see
Chapter 2).
Much of generally accepted medical practice has not been systematically evaluated. For
example: “Of around 2500 treatments covered [in BMJ Clinical Evidence] 13% are rated as
benecial, 23% likely to be benecial, 8% as trade off between benets and harms, 6%
unlikely to be benecial, 4% likely to be ineffective or harmful, and 46%, the largest proportion, as
unknown effectiveness [italics added].”178
Individuals studied in RCTs do not reect the patient population seen most often in primary
care; condence in the transferability of the data is thereby reduced.179
“Randomized trials, especially if evaluating complex interventions or with strict inclusion/
exclusion criteria, often only provide data in a clinical context that does not exist outside
the trial itself and have limited power to detect harm…. Systematic reviews require vigilant
interpretation and should not necessarily be considered as high level evidence due to issues
related to … incomplete reporting and the inclusion of evidence from trials of poor quality….
Meta-analyses are not primary evidence; they are statistically assisted interpretations of
ixClinical guidelines are “systematically developed statements to assist practitioner and patient decisions about appropriate
health care for specic clinical circumstances”—Institute of Medicine, 1990. “They dene the role of specic diagnostic and
treatment modalities in the diagnosis and management of patients. The statements contain recommendations that are based
on evidence from a rigorous systematic review and synthesis of the published medical literature”— http://www.nhlbi.nih.gov/
guidelines/about.htm.
21st Century Medicine | 37
primary evidence. They have been shown to contradict conrmatory trials, especially when
such meta-analyses are based upon small, low quality studies.”180
“Even the most promising ndings of basic research take a long time to translate into clinical
experimentation, and adoption in clinical practice is rare.”181 Evidence-based guidelines of
genomic applications are even more rare, and thus are unavailable to practitioners who rely
on EBM processes to update their clinical practices.182
Common ground with other emerging models
EBM is, to differing degrees, part of all the other models described in this paper. Since EBM focuses
primarily on mechanisms for translating research ndings into clinical applications, it is less useful for
those aspects of personalized medicine and systems biology that concentrate on the basic research itself.
Also, as noted above, integrating personalized assessment and treatment with EBM models is not yet
feasible on a systematic basis. It will be extremely interesting to see whether this can be done.
Role in a synthesized, comprehensive model of 21st century medicine
In our opinion, the role of EBM is strongest in acute-care situations, where the physician or healthcare
team must focus on short-term and fairly narrowly dened issues. When we consider its role in outpatient
primary care for complex, chronic disease, however, it is more difcult to make an overall determination
of usefulness. Certainly there are situations where EBM and the clinical guidelines that ow out of it
are extremely useful. In general, however, it seems easier to see the problems (described above) than it
is to detect the benets. Nonetheless, there is great benet to researchers, practitioners, and patients in
improving our ability to objectively and systematically evaluate data and determine clinical usefulness.
Overall, this is perhaps the most important role that EBM will play over time.
Systems Biology
What is it?
Although there is not yet a universally recognized denition of systems biology, the National Institute
of General Medical Services (NIGMS) at NIH provides the following explanation: “A eld that seeks to
study the relationships and interactions between various parts of a biological system (metabolic pathways,
organelles, cells, and organisms) and to integrate this information to understand how biological systems
function.”183 The Molecular Systems Biology Blog on Systems & Synthetic Biology poses—and provides some
possible answers to—the question of why it appears to be difcult to come up with a concise and generally
applicable denition: “One of the reasons might be that every denition has to respect a delicate balance
between ‘the yin and the yang’ of the discipline: the integration of experimental and computational
approaches; the balance between genome-wide systematical approaches and smaller-scale quantitative
studies; top-down versus bottom-up strategies to solve systems architecture and functional properties.”
The blog hypothesizes that, “despite the diversity in opinions and views, there might be two main aspects
that are conserved across these denitions: a) a system-level approach attempts to consider all the components
emerging mOdels
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38 | 21st Century Medicine
of a system; b) the properties and interactions of the components are linked with functions performed by
the intact system via a computational model.”184
We would add to the NIGMS denition that it is also vital to understand how the human system interacts
with the environment, as well as how all the components act and interact. We see systems biology as
a broad term for the basic science underlying the personalized medicine revolution (described above).
While the elds of personalized, prospective, and integrative medicine all recognize (to varying degrees)
the importance of nutritional genomics, pharmacogenomics, metabolomics, and proteomics to the future
of health care, most of the scientic research has been generated by systems biologists (whether or not
they identify with that term or any of the many denitions proposed). Thus far, although systems biology
claims virtually the same broad territory as personalized medicine, it actually focuses almost exclusively
on pharmacogenomics—in the Willie Sutton idiom, “That’s where the money is.” Attention to the
applicability of those ndings to patient care (i.e., the gene-environment interaction that creates the
phenotype) is what connects systems biology to personalized medicine.
Strengths and weaknesses
Identifying the nature and effects of the myriad interactions that occur where human biology is exposed
to the environment is almost unimaginably complex. Yet that effort is critical to a better understanding of
the multifactorial nature of disease development. We know that “the causes of most chronic diseases will
require an understanding of both the genetic and environmental contribution to their etiology…. The
most critical issue is how to relate exposure-disease association studies to pathways and mechanisms….
Scientists will need tools with the capacity to monitor the global expression of thousands of genes,
proteins and metabolites simultaneously…. Even when all the highly relevant genes and their interactions
with specic environmental components have been identied, it will still be difcult to relate the inuence
of an individual’s genotype to their disease phenotype due to the added complexity of gene-gene
interactions, post-translational processing, and protein-protein interactions.”185
Because of the magnitude and complexity of the challenge, “Systems biology research should create
an interactive inter-disciplinary scientic culture. For progress to occur, experts in engineering, physics,
mathematics, and computer science must join biochemists, cell biologists, and physiologists in the effort
to gure out how to obtain the required data and develop the sophisticated computational approaches
that will be needed to make viable predictions.”186 This is a long-term prospect, of course, although early
studies have shown some highly benecial outcomes of genomic medicine187 (a plausible term for applying
the ndings of systems biology to patient care).
Many of the same obstacles discussed earlier in this chapter vis-à-vis personalized medicine and
pharmacogenomics188 are inherently shared by systems biology. In addition to barriers of cost, complexity,
equipment, ethics, and education, “the evidence and importance of most pharmacogenomics associations
are not sufcient to overcome the barriers to clinical implementation…. It is likely that complementary
technologies, such as metabonomics, will be able to compensate for some limitations of genotype-
phenotype association.”189
21st Century Medicine | 39
Common ground with other emerging models
Systems biology seeks to elucidate the biological underpinnings of disease risk and apply that knowledge
within a personalized, predictive, prospective, and participatory model of patient care. The science of
systems biology clearly underlines the congruent goals of personalized medicine, prospective medicine,
and—to a lesser extent—integrative medicine. It is not entirely congruent with evidence-based medicine,
because it has not yet generated a large number of clinical trials. In fact, systems biology somewhat
reverses the direction of EBM described above, in that it takes us back to a more “pathophysiological
rationale” of disease and treatment. Eventually, research models will be devised to test the effectiveness
and reliability of patient care based on diagnostic tests and therapeutic recommendations derived from
systems biology.
Role in a synthesized, comprehensive model of 21st century medicine
Systems biology illuminates the science that will support a new model of health care—one that is based on
an intimate understanding of complex human systems interacting with complex environments and unique
genetic inheritances.190 In order to achieve its greatest potential, it must broaden its scope far beyond
pharmacogenomics, which represents a very small portion of what we need to know about preventing and
treating complex, chronic disease.
Integrative Medicine
What is it?
“Integrative medicine can be dened as an approach to the practice of medicine that makes use of
the best available evidence taking into account the whole person (body, mind, and spirit), including all
aspects of lifestyle. It emphasizes the therapeutic relationship and makes use of both conventional and
complementary/alternative approaches.”191 The eld is now nearly 10 years old and it is the only one of
the emerging models discussed in this paper to explicitly encompass the integration of therapeutics that,
until recently, were the sole purview of complementary and alternative medicinex (CAM). A number of
forces are responsible for the emergence of this new discipline:
The initial driver was undoubtedly the burgeoning interest in and demand for CAM displayed
by consumers over many years. As reported in the Annals of Internal Medicine in 2001, “Use
of CAM therapies by a large proportion of the study sample is the result of a secular trend
that began at least a half century ago. This trend suggests a continuing demand for CAM
therapies that will affect health care delivery for the foreseeable future.”192
The establishment of the NIH National Center for Complementary and Alternative Medicine
(NCCAM) provided research funding to investigate CAM therapies. As research into CAM
therapies revealed many effective natural (nonpharmaceutical, nonsurgical) approaches to
xA widely used denition of CAM therapies from the Osher Institute at Harvard: “clinical services not routinely used within
conventional care, such as chiropractic, acupuncture, massage therapy, homeopathy, meditation, music therapy, therapeutic
touch, yoga, Reiki, and advice involving herbal products and other dietary supplements.”
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Meditation and Brain
Science
Meditation may be one of the best
studied body-mind modalities.
The effects of meditation on the
brain have been studied using
sophisticated functional MRI (fMRI)
and electroencephalographic (EEG)
techniques. Not only have researchers
detected signicant differences in
brain activity between experienced
meditators and nonmeditators (or
inexperienced meditators), but there
also may be detectable differences
resulting from the particular type of
meditation studied.199 Although more
substantial differences can be found
with long-term meditators, even a
short training period of eight weeks
“produces demonstrable effects on
brain and immune function.”200 Some
ndings suggest that “the resting state
of the brain may be altered by long-
term meditative practice,” and that
“attention and affective processes…are
exible skills that can be trained.”201
The practical implications of such
ndings, if replicated on a large
scale, could be considerable. One
report concluded that “it is plausible
from our results that meditation
may strengthen the ability to inhibit
cognitive and emotional mental
processes such as rumination that can
lead to or exacerbate stress, anxiety, or
depression.”202 A subsequent study to
test this hypothesis returned startling
results203:
MBCT [mindfulness-based cognitive
therapy] was more effective
than m-ADM [maintenance
antidepressant medication] in
reducing residual depressive
a wide variety of diseases and conditions, it was
thought desirable for physicians to understand CAM
in much greater depth193 and to devise a pathway for
validated approaches to be brought into the standard
“medicine chest.”194
The philanthropic funding of centers and
departments of integrative medicine within the
academic medicine community (e.g., University of
Arizona, Harvard, Vanderbilt, Duke; also see list in
the Appendix of members of the Consortium of
Academic Health Centers for Integrative Medicine)
brought high-level attention to the educational
element: “Integration of CAM with conventional
health care requires educational venues that
prepare conventionally trained caregivers with a
sufcient knowledge base for assessing benecial
and detrimental interactions between CAM and
conventional care approaches; development of
criteria for making informed referrals to CAM
practitioners; and enhanced research capacity.”195
Integrative medicine might also be characterized
as a response to the increasing depersonalization
of health care that came with the rise of HMOs,
greater use of technology, decreasing time spent in
the outpatient visit, and the insertion of third-party
payers into the doctor-patient relationship.196
Integrative medicine curriculums now commonly describe a
fairly comprehensive set of core competencies that include
dietary interventions, nutraceuticals, botanical medicines,
body-mind practices (see, for example, Sidebar on meditation),
energy medicine (e.g., acupuncture), and manual medicine (e.g.,
massage, chiropractic).197, 198 The balance of didactic knowledge
(for the purpose of providing better-informed advice and
referrals to patients) vs. practical skills (for actually integrating
clinical applications) varies from program to program.
Strengths and weaknesses
Integrative medicine is an important step toward a functionally
integrated healthcare system that includes all appropriately
credentialed practitioners. Not only does it provide an avenue for
validated CAM therapies to be more widely used, but it supports
21st Century Medicine | 41
symptoms and psychiatric
comorbidity and in improving
quality of life in the physical and
psychological domains. There was
no difference in average annual cost
between the two groups. Rates of
ADM usage in the MBCT group
was [sic] signicantly reduced,
and 46 patients (75%) completely
discontinued their ADM. For patients
treated with ADM, MBCT may
provide an alternative approach for
relapse prevention.
the interdisciplinary team concept in both educational and
clinical settings. It allows patients greater freedom of choice in
both therapies and providers, and it encourages dialogue among
all health practitioners.
There is a danger that integrative medicine physicians will
extend their practices beyond the scope of their education.
Completing a program in integrative medicine does not turn
an MD or a DO into a trained chiropractor, acupuncturist,
naturopathic physician, or other such practitioner. It is important
that those who wish to fully practice an alternative discipline seek
comprehensive training from accredited institutions, just as those
who wish to practice as medical doctors must do.
Common ground with other emerging models
Integrated medicine uses evidence-based medicine to select
the practices to integrate. It is multidisciplinary and oriented
toward whole-person health care. It is the only one of the
models to explicitly integrate alternative practitioners and
approaches, to emphasize the importance of the practitioner-
patient relationship, and to bring body-mind issues to the fore.
Other than EBM, it is the only one that already has a signicant
foothold within academic medicine.
Role in a synthesized, comprehensive model of
21st century medicine
Integrative medicine provides great leadership in demonstrating
the importance of a more integrated healthcare system and in
creating academic models to educate practitioners in this new
approach. It could benet from a greater emphasis on genomic
medicine, perhaps by incorporating some of the principles or
recommendations of personalized or prospective medicine.
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42 | 21st Century Medicine
21st Century Medicine | 43
21st
century
medicine:
A New Model for Medical
Education and Practice
Chapter 4
________________________________________
The Clinician’s Dilemma
[W]hat we observe is not nature itself, but nature exposed to our method of questioning.
Natural science, does not simply describe and explain nature;
it is part of the interplay between nature and ourselves.
—WeRneR heiSenBeRg, phySicS and philoSophy, 1958
We have spent, to this point, a great deal of time and effort exploring both the
challenge of 21st century medicine—to rst halt and then reverse the epidemic
of chronic disease—and some of the most prominent among many proposed
solutions. We hope we have achieved a shared recognition that our current tools
and approaches are not sufcient to the task, and that changes in the practice
of medicine are necessary and imminent. At the same time, we cannot ignore
the challenge of making these conclusions relevant to the individual practice
of medicine. For, ultimately, most health care is delivered one patient and one
practitioner at a time. In this chapter, we explore the clinician’s dilemma: how
to practice in such a way that both the continuing advances of science and
the essential art of medicine are integrated seamlessly into clinical practice,
neither overshadowing the other. It won’t matter how intelligent and persuasive
the arguments for change may be if we cannot convert them into practical
approaches that can be taught to and adopted by individual clinicians.
This paper is not intended as an exploration of the actual clinical interventions
that comprise functional medicine nor of the extensive science that underlies
them. For that purpose, we refer the reader to the books, monographs, and
courses available through The Institute for Functional Medicine (IFM).xi In these
nal two chapters, we address clinical practice at a different level, presenting the
foundational concepts and principles that we believe should shape the coming
changes in health care.
xiA complete list of IFM publications and courses can be found at www.functionalmedicine.org.
44 | 21st Century Medicine
21st century medicine:
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xiiThe potential for human cloning might be considered the exception to this rule. However, exact replication from a clone donor
cannot duplicate the pre and post epigenetic imprinting that skews the exactness of a clone.
The Central Hub of 21st Century Medicine
The primary principle around which 21st century medicine—functional medicine—will revolve is
personalized, systems medicine. Grouping people into categories based on organ system diseases, and then
prescribing as though all people with a given diagnosis were inherently alike, is beginning to give way to a
model that recognizes each patient’s genetic and environmental uniqueness. Clinicians must develop the
knowledge and skills to deliver individually tailored care. They must be able (and willing) to incorporate
the science of systems biology, the emerging discipline of personalized care, and a much broader array of
assessment, therapeutic, and preventive strategies into a new therapeutic relationship.
Each human emerges from a mold that has but one model.xii Uniqueness continues to develop
throughout life as a result of myriad inuences. Family, school, work, community, diet, exercise, stress,
and environmental toxicity all communicate information from outside the organism to the epigenetic
translational structures that are married to nuclear DNA and that create powerful downstream effects on
the genome, proteome, and metabolome. This phenomenon of biochemical uniqueness was recognized,
researched, and documented in the 20th century, and is the foundation from which many key constructs
have evolved, including systems biology and systems medicine, prospective health care, patient-centered
health care, nutrigenomics, pharmacogenomics, proteomics, and metabolomics/metabonomics (see
Chapter 3).
Decision Making in the Face of Uncertainty
From this chaotic, nonlinear interplay of complex factors, involving the integration of both genetics and
context of living, emerges the haunting reality that all care is provided in a context of uncertainty. This is
the shadow side of modern clinical medicine and it poses a daunting conundrum—how do you structure
and systematize the assessment and treatment of patients when each is the product of a multitude of
unique genetic and environmental inuences and interactions? Kathryn Montgomery in her scholarly
book, How Doctors Think, directly addresses this challenging issue:
Complexity and uncertainty are built into the physician’s effort to understand the particular in
light of general rules…. The obstacle they encounter is the radical uncertainty of clinical practice:
not just the incompleteness of medical knowledge but, more important, the imprecision of the
application of even the most solid-seeming fact to a particular patient.204
What elevates the importance (and the stress) of clinical care over the work of, for instance, engineers,
lawyers, accountants, and other nonclinical professionals is its continuous involvement in matters of
life and death. The cost of failure is so high—death, when life might have been possible; illness, when
health might have been attainable. The daily unconscious concern of every clinician is the weight of
this cumulative decision making—inherently uncertain and lacking full (or sometimes even adequate)
information to inform the clinical picture. Dr. Jerome Groopman in his provocative book with the same
title, How Doctors Think, addressed this issue from his clinical perspective:
the cliniciAn’s dilemmA
21st Century Medicine | 45
Uncertainty creeps into medical practice through every pore. Whether a physician is dening a
disease, making a diagnosis, selecting a procedure, observing outcomes, assessing probabilities,
assigning preferences, or putting it all together, he is walking on very slippery terrain. It is
difcult for non-physicians, and for many physicians, to appreciate how complex these tasks
are, how poorly we understand them, and how easy it is for honest people to come to different
conclusions.205
Personalized, systems medicine serves to inform us about the enormity of the uncertainty. The message
is clear: there is no one-size-ts-all solution to resolve any specic diagnosis. The limitations of clinical
algorithms and evidence-based medicine can now be more clearly discerned. We can no longer allow
them to skew our understanding of the larger picture, however difcult it may be to look at uninchingly.
We are at a crossroads where only honesty about the limitations of strategies that seek to avoid or ignore
uncertainty will sufce.
For the great enemy of truth is very often not the lie—deliberate, contrived, and dishonest—but
the myth—persistent, persuasive, and unrealistic. Too often we hold fast to the clichés of our
forbears. We subject all facts to a prefabricated set of interpretations. We enjoy the comfort of
opinion without the discomfort of thought.
—John F. Kennedy, yale commencement, 1962
Medicine has attempted historically, through a number of shifts in perspective, to provide greater certainty
to both practicing clinicians and patients, a patently valuable goal. Setting aside traditional methods
of instilling condence—oracles or shamans, for example—science has been a very important tool for
reducing uncertainty.
Twentieth century medicine completed a great philosophical and practical transformation into the organ
system model of disease and diagnosis. This provided an evolving and reassuring sense of control and
certainty as a result of ever-increasing specialization (often described as knowing more and more about
less and less) as well as myriad fascinating scientic breakthroughs in understanding the nature of life,
health, and disease. From early x-rays through the sophisticated imaging processes in use today, through
ever more complex and detailed biochemical pathways, we have explored the silos of mammalian
organ systems taxonomy. Objective facts accreted in uncountable numbers during the 1900s, describing
human anatomy, physiology, and mechanisms of dysfunction from the cellular level to the specic organs
themselves. The medical specialties (e.g., cardiology, neurology, nephrology) emerged and grew strong
from these historic breakthroughs.
Near the end of the 20th century, however, the reality of the web-like, chaotic, nonlinear and complex
nature of life (and health)—exposed by advances in the systems-oriented life sciences—began to erode
this reassuring sense of certainty. Twenty-rst century medicine has now come face-to-face with the
practical implications of uncertainty—a problem that ummoxed many mid-20th century physicists
(including the great Albert Einstein, who ultimately rejected what is now an accepted principle) when
they rst confronted Heisenberg’s articulation of the principle of uncertainty in physics. Fortunately, once
the seriousness of this issue is consciously acknowledged, management strategies can be developed. First,
however, we have to stop denying the presence and power of uncertainty in medicine. Research by brain
scientists using advanced imaging and electronic technologies and analytic techniques equips the clinician
with important knowledge for facing squarely the daunting task of assessing and treating each patient as
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a unique individual, shaped by innumerable complex interactions between genetics and the cumulative
inuences of daily life.
The rest of this chapter will discuss these ndings and will describe why the context of uncertainty in
medicine requires a change in our view of evidence and the therapeutic relationship, and a considerable
expansion in the clinical tool kit of the practitioner. The increasingly technical (and increasingly brief)
clinical encounter that has characterized the last few decades in medicine can be transformed into
a healing partnership through the appropriate integration of relevant evidence from clinical trials, the
knowledge gained from breakthroughs in brain science and systems biology, and an expanded clinical
armamentarium. Within this complex relational system can be found effective strategies for individualized
assessment and treatment, taking into account the uncertainty generated by the complex genetic and
environmental uniqueness of each patient—we can, in fact, begin the practice of personalized, systems
medicine today.206, 207
Evidence-based Medicine in the Clinical Setting: Uses and Limitations
The scientic method disciplines the creative process of human inquiry. In the applied biological sciences
(e.g., clinical medicine) prior to World War II, evaluation of emerging therapeutics was mainly the
purview of recognized leaders in the medical profession, based primarily on their clinical experience and
reputations, and without the rigor of systematic controls or external standards.208 To improve the quality
of evidence and render a more accurate judgment with less personal bias, postwar researchers developed
the randomized controlled trial (RCT) protocol. The major characteristics of this method include blinded
assessment (of subjects, investigators, or both), often in the presence of a placebo control; random
assignment to comparable groups; and inferential statistics as a surrogate for establishing causation.209
The reliance on the expert gave way to reliance on results from RCTs. Clinicians could no longer reduce
uncertainty by following the lead of a condent expert, but they increasingly appreciated the power of the
double-blind, randomized, placebo-controlled clinical trial—a step up in certitude.210, 211 Putting aside, for
the moment, the many problems inherent in the RCT model, not the least of which is the bias introduced
by the inuence of big Pharma,212, 213, 214, 215 let’s briey explore EBM—the offspring of the RCT model—
as understood and used by clinicians to reduce uncertainty.
Proponents of the RCT as the gold standard for unbiased research results have fostered its preeminence
in the applied medical elds, both in primary and specialty care. They have argued for and developed
algorithms for grading recommendations based on a research quality scale that ranks methodologies in
descending order of accepted best evidence:216, 217
Systematic reviews and meta-analyses of RCT studies
RCTs
Nonrandomized intervention studies
Nonexperimental studies
Expert opinion
21st Century Medicine | 47
Amid the early excitement generated by this new schema, certain assumptions were posited as
foundational:
A new paradigm for medical practice is emerging. Evidence-based medicine de-emphasizes intuition,
unsystematic clinical experience, and pathophysiologic rationale as sufcient grounds for clinical decision making and
stresses the examination of evidence from clinical research. Evidence-based medicine requires new
skills of the physician including efcient literature searching and the application of formal rules of
evidence evaluating the clinical literature.218 [Italics added.]
—evidence-BaSed medicine WoRKing gRoup, Jama, 1992
The application of EBM in the clinical setting is described as following this general scenario:219, 220
Select specic clinical questions from the patient’s problem(s)
Search the literature or databases for relevant clinical information
Appraise the evidence for:
➢validity against the hierarchy of evidence as described above, and
➢usefulness to the patient and practice
Implement useful ndings in everyday practice
Arguments in favor of EBM infusion into both medical education and clinical practice are based on the
following facts and inferences:221, 222
Available new evidence can and should lead to major changes in patient care
Practicing physicians often fail to obtain available newer relevant evidence
Medical knowledge and clinical performance deteriorate over time without the leavening of
newer evidence inuencing clinical decisions
Traditional continuing medical education (CME) alone is inefcient and generally does not
improve clinical performance without signicant follow-up and evaluation measures
The discipline of using evidence-based medicine can keep clinicians up-to-date
In a cogent paper in The Lancet in 1999, van Weel and Knottnerus responded to the proddings of many
eminent medical thought leaders to move ahead quickly and comprehensively with the integration of
EBM into the clinical setting by pointing out the many difculties of using this schema to manage the care
of individual patients with complex, chronic illness:223
EBM tends to concentrate on research methodology and reduces clinical practice to the
technical implementation of research ndings. In a more colloquial view, it is the tail wagging
the dog. Rather than using clinical judgment to guide the choice of relevant evidence, EBM is
structured with a hierarchy of evidence as the driver of clinical judgment.
the cliniciAn’s dilemmA
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The structure of RCT methodology assumes the consequences of individual variability in
response to treatment will “wash out” if the subject pool is large enough and the statistical
analyses sophisticated enough. While this may be true for populations, it seriously limits the applicability
of the research in primary care, where therapy is delivered one unique patient at a time.
Co-morbid conditions are the usual justied reason for the exclusion of many patients from
RCTs, so the very patients most in need of usable evidence (e.g., those with complex, chronic conditions) are
often not in the cohorts of patients being studied, making the ndings from the research trials very
limited in their applicability.
In primary care, treatment usually involves several interventions, sometimes delivered
concurrently and sometimes sequentially. Unfortunately, combinations of evidence-based
interventions do not sum to a treatment plan that is evidence-based. Interactions between
single interventions may increase or decrease their efcacy (even under ideal trial conditions),
when blended into a comprehensive plan. Adverse interactions among treatments may, and
often do, occur.
Clinical research does not focus on the overall outcome of composite interventions because
of the complexity of such studies and the absence of well-developed tools for studying such
whole systems approaches.
Drug interventions have been studied more extensively than nonpharmacological
interventions, in part due to the technical and methodological difculties in the design of
RCTs for nondrug interventions (and, in part, because of the nonpatentable nature of most
lifestyle interventions). This situation creates a signicant problem in primary care, where the
use of educational, dietary, and lifestyle interventions is attractive because of their resonance
with the principle of “maximum effect using minimum resources.”
In marked contrast to the assertions of the EBM Working Group cited earlier, van Weel and Knottnerus
suggest that the driving force behind EBM should be a coherent system of fundamental research
in pathophysiology and the humanities, combined with careful clinical observations, on which systematic
(RCT-based) evidence of effectiveness is superimposed. Existing clinical practice should be supported
or, if erroneous, corrected on the basis of this coherent system. They go on to propose that “two
complementary approaches are needed to strengthen the evidence base of nonpharmacological
interventions and complex multifaceted strategies. First, the generic characteristics of complex
interventions must be acknowledged as essential for its evaluation. Second, a methodology to allow the
assessment of complex effects should be further developed.”
Dr. David Mant in his seminal 1999 paper, “Can randomized trials inform clinical decisions about
individual patients?” takes a slightly different tack in exploring the irony that the RCT combines strength
of concept for the population being studied with weakness of specic application to the individual
patient:224
21st Century Medicine | 49
The paradox of the clinical trial is that it is the best way to assess whether an intervention works,
but is arguably the worst way to assess who will benet from it…. However, the nub of the
argument for me is that randomized controlled trials are primarily about medical interventions
and not patients. In clinical trials, patients are randomized to allow a comparison of intervention
efcacy unbiased by the individuality of patient. This methodological approach provides society
with powerful protection against witch-doctoring, and helps us eliminate the inefciencies in the
provision of medical care described by Cochrane. But the methodological minimization of information on
effectiveness in relation to the individual patient leaves an evidence gap for clinicians. [Italics added.]
Dr. Alan Feinstein, from the Department of Medicine at Yale University, echoes similar reservations in his
article, “Problems in the evidence of evidence-based medicine.”225 Larry Culpepper and Thomas Gilbert,
in their Lancet commentary, “Evidence and ethics,” focus on this same difculty in the primary-care
arena.226 Although the debate has continued over the past decade, these reasoned arguments have been
heard less frequently as the push toward EBM has gained momentum. However, the problems described
above have not been solved. Rather, with the advent of personalized medicine and systems biology, it
is even more clear that the reductionist simplicity of the RCT frequently does not work to address the
signicant questions now facing 21st century practitioners in their struggle to cope with the epidemic of
complex, chronic disease.227, 228, 229, 230, 231
We can now begin to understand why the effect of research ndings on clinical practice has been
weaker than the early proponents of EBM postulated. The rst problem that has impeded the successful
application of EBM to patient care is the complex nature of the translation of research studies to the
individual patient’s unique clinical problem(s)—what Larry Weed called knowledge coupling.232, 233
John Hampton, Professor of Cardiology, University Hospital, Nottingham, England, in a review titled
“Evidence-based medicine, opinion-based medicine, and real-world medicine,” reasons: “Clinical trials
will tell us what treatments are effective, but not necessarily which patients should receive them…Treatment must always
be tailored to the individual patient.”234 (We would add to that statement that RCTs can only tell us what
treatments are effective from among those studied. The decision about what to investigate introduces so much
bias into the evidence base that it would be difcult to overstate its impact.)
Added to this methodological conundrum are the real-world exigencies of daily clinical practice that
make it virtually impossible to acquire, collate, and lter all relevant evidence prior to direct application
to the unique needs of the patient. Imagine a clinic where, after each therapeutic encounter—involving
both appropriate history taking and physical examination procedures—a problem list is developed and
then carefully subjected to a medical literature search and analysis. The pace of clinical practice will not
tolerate the inertia of such a process,235 even to improve the care of patients who may be in desperate
need of new interventions based on emerging evidence.
A second major issue is even more complex. If medical care were as simple as making a diagnosis and
then prescribing an appropriate pharmacologic agent (or agents), then the EBM system, as presently
congured and applied, might work—but only if appropriate Problem Oriented Evidence that Matters
(POEMs) xiii, 236 were available for each medical problem (and disregarding, for the moment, that
xiiiTo assist the practicing physician’s effective inclusion of new evidence into daily practice, both government-sponsored and
commercially afliated organizations have moved EBM forward with a collation of ltered studies called: Problem Oriented
Evidence that Matters (POEMs). Most POEMs and most studies in the Cochrane Collection are research trials of pharmacologic
therapeutic interventions. It is now possible to search these specic databases, or self-developed relevant databases that review
groups of studies that directly link research ndings with specic clinical problems.
the cliniciAn’s dilemmA
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most chronic disease is complicated by multiple comorbidities that are rarely addressed by POEMs).
Unfortunately, the “better living through chemistry” dream that fueled half a century of research has
not, in fact, created a healthier population (see Chapter 2).237 Although many acute medical problems
do appear to respond consistently as envisioned by the EBM model, more than 70% of health problems
presenting to clinicians today are both chronic and complex238 (Chapter 2), and they require a different
approach. “Treating only known biological components of disease minimizes the ability of the
practitioner to tailor therapeutic interventions to individual patients.”239
Despite these sobering facts, physician education, training, and reimbursement, as well as research
designs for clinical studies that physicians depend upon for effective decision making, continue to be
focused primarily on an acute-care model that emphasizes pharmacologic solutions for complex, chronic
problems, leaving the discerning clinician without the evidence and tools needed for addressing their
patients’ complex needs.
It’s not enough, of course, for us to understand what’s wrong. We must also seek better solutions for
these urgent problems, regardless of the difculty of the task and the elusiveness of the answers. The
RCT tool was developed during a specic period in our medical history and worked well to differentiate
the traditionalists, who claimed that clinical experience trumped bench science, from the scientists, who
perceived the value in systematic inquiry. Major strides in treatment have occurred in the intervening 50
to 60 years as a result of the shift toward the use of RCT methodology. But we are now at another nodal
decision point, unique to our cultural and medical evolution. We need more sophisticated tools to shed
light on the nature of the web-like interweaving of mechanisms at work in complex, chronic
illness.240, 241, 242 While alternate study designs and statistical methodologies are being developed for
analyzing complex data sets,243, 244, 245 we must return the practice of EBM to its original mission of using
evidence to inform clinical experience and to expand the understanding of basic mechanisms of health
and disease.246, 247 This will help to reverse the decade-long plunge toward “... reducing clinical practice to
the technical implementation of research ndings.”248, 249
In sum, we are now facing another major transition in how we perceive and utilize evidence in clinical
medicine. Thomas Kuhn offers this insightful analysis:
When defects in an existing paradigm accumulate to the extent that the paradigm is no longer
tenable, the paradigm is challenged and replaced by a new way of looking at the world. Medical
practice is changing, and the change, which involves using the medical literature more effectively in
guiding medical practice, is profound enough that it can appropriately be called a paradigm shift.250
A Science-Using Profession
Given the serious limitations of applying the EBM model in clinical practice, we must ask two questions
central to the future of medicine:
How do we develop an effective therapeutic relationship based upon (1) efcacious,
reproducible, and personalized clinical applications that are solidly anchored in science, (2)
emerging knowledge about the multifactorial causes of chronic disease, and (3) an expanded
awareness of the nature of clinical/critical thinking?
21st Century Medicine | 51
How do we transition from an EBM-based, guideline-driven, prescriptive clinical practice to
an individualized, patient-centered approach that captures both the science and the art of
medicine?
First, we must recognize that most clinicians, by professional training and inclination, are not scientists.
Clinical medicine is a science-using profession. It is true that diagnosis and treatment have become
intensely science-using activities, but these activities have a distinctly different process and endpoint
than those of the professional scientist.251 “Physicians start from the demands of the patient’s condition
and not from the demand for generalizable knowledge, and their goal is just as particular: to treat the
patient’s illness, not to test the therapy.”252 The evidence needs of clinical medicine are also distinctly
different. The focus on application and usefulness centers on how the evidence informs the assessment and
treatment process for each individual patient, given that patient’s unique genetic propensities and unique
environmental inuences.
At a number of points in this paper, we have documented how most clinical evidence based on RCTs
informs about cohorts of patients with similar signs and symptoms (the basis of diagnosis and diagnostic
groups), but not does not necessarily provide decision support for an individual patient. The primary
responsibility of the attending clinician is to ferret out meaningful evidence for each patient, knowing that
unique genomic specicities may predispose that patient to unanticipated results. From this perspective,
evidence often serves to qualify insight, but when applied in a simplistic or statistically linear way, can create
unintended mischief.253 From this perspective, every maneuver, either further assessment or therapeutic
intervention, becomes a clinical probe that must be assessed in partnership with the client as the shared
journey of investigation and healing proceeds.
Dr. Sackett, founder and advocate for EBM, was quite clear about this in the early development of EBM:
“Evidence based medicine is the conscientious, explicit, and judicious use of current best evidence in
making decisions about the care of individual patients. The practice of evidence based medicine means
integrating individual clinical expertise with the best available external clinical evidence from systematic
research…. Good doctors use both individual clinical expertise and the best available external evidence and neither alone is
enough.”254 [Italics added.]
The combining of these elements can be viewed as a Venn diagram, where the best outcomes occur when
all three elements are represented (Figure 9).
Research
Evidence
Clinical
Practice
The Patient’s Story
Optimal
Outcomes
Figure 9:
Optimal Outcomes: Applying Evidence-based Medicine to the Real World
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Another Perspective on the
Biomedical Model
The complexity of the developing
explanatory models has been serially
addressed in the Annals of Family
Medicine, a peer-reviewed medical
journal “dedicated to advancing
knowledge essential to understanding
and improving health and primary
care,” including the development of
methodology and theory for addressing
this conundrum. In the article, “The
biopsychosocial model 25 years later:
Principles, practice, and scientic
inquiry,”255 the authors critique
the limitations of the conventional
biomedical model and the research
methodologies that evolve from this
model and preview the evolving model
of complexity and causality and the
nested model of structural causality:
Few morbid conditions could
be interpreted as being of the
nature “one microbe, one illness”;
rather, there are usually multiple
interacting causes and contributing
factors. Thus, obesity leads to
both diabetes and arthritis; both
obesity and arthritis limit exercise
capacity, adversely affecting blood
pressure and cholesterol levels; and
all of the above, except perhaps
arthritis, contribute to both stroke
and coronary artery disease. Some
effects (depression after a heart
attack or stroke) can then become
causal (greater likelihood of a second
similar event)….These observations
set the stage for models of circular
causality that describe how a series
of feedback loops sustain a specic
pattern of behavior over
time.256, 257, 258 Complexity science
is an attempt to understand these
complex recursive and emergent
properties of systems259, 260 and to
nd interrelated proximal causes that
might be changed with the right set
of interventions.261
David Deutsch, in The Fabric of Reality, describes the need for a
next step in using the science of underlying pathophysiological
mechanisms of disease in the clinical setting of medicine:
The science of medicine is perhaps the most
frequently cited case of increasing specialization
seeming to follow inevitably from increasing
knowledge, as new cures and better treatments
for more diseases are discovered. But as medical
and biochemical research comes up with deeper
explanations of disease processes (and healthy
processes) in the body, understanding is also on the
increase. More general concepts are replacing more
specic ones as common, underlying molecular
mechanisms are found for dissimilar diseases in
different parts of the body. Once a disease can be
understood as tting into a general framework, the
role of the specialist diminishes.... Physicians…
can look up such facts as are known. But [more
importantly] they may be able to apply a general
theory to work out the required treatment, and
expect it to be effective even if it has never been
used before.262
The real question now facing every discerning, informed
clinician263 is how to bring relevant, graded, emerging scientic
evidence to the complex list of problems made unique by the
patient’s genetic susceptibilities and potentialities that, in turn,
communicate constantly with the ever-changing environment
within which the patient lives. No RCT can inform, in a
specic way, the appropriate clinical roadmap for assessment
and planning for therapeutic interventions in this complex
environment.264 Clinicians must use science; it is a powerful tool.
But they should be in charge of how and when to use it, not
dominated and intimidated by it.
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The Heuristics that Guide Doctors’ Thinking
We believe it is fair to say that the fear of uncertainty has led us to narrow our eld of vision far too soon.
“Science has not one method, but many. These include observation in the natural world, experimentation
in the laboratory, mathematical proof, computer simulation with real data, analysis of surveys and
demographical statistics, and thought experiments for the great geniuses, such as Galileo and Einstein.
In the social sciences, a climate of anxious identication with a sub-discipline goes hand in hand with
methodological rituals … methodological uniformity and discipline-oriented research are two sides of the
same coin....” A shift is needed to “free us from the straightjacket of methodological rituals, allowing us
to consider and choose proper methodologies for the problem at hand and to verify a result obtained with
one method by using other methods.”265
Has broad-based and open-minded scientic inquiry been skewed by EBM and its hierarchy of evidence
codication and ranking?266, 267, 268, 269, 270, 271 Is the hegemony of EBM in contemporary medicine, as
exemplied by Drs. Montori and Guyatt,272 closing the door on the reintegration of the science and
art of medicine?xiv We need to ask what we have surrendered by de-emphasizing “unsystematic clinical
experience and pathophysiologic rationale.” What is the irreplaceable loss in patient outcomes with the
dismissing of experience, intuition, and wisdom? What must we do to develop skills and methodologies
appropriate to clinical decision making in a context of uncertainty?
There is a robust literature that explores the actual methodologies used by clinicians who must make
decisions when time and information are limited and the outcome is uncertain. It is clear from brain
research that there is an important difference between the human brain and other features of the universe.
The brain is a complicated, nonlinear, living system capable of self-organization. The brain does not
respond to incoming stimuli in a direct, reex-like action but continuously changes, constructing its own
neural activity patterns in order to adapt to and synchronize with external stimuli. Genetic makeup and
continuous stimuli from the environment are the only factors that create individual differences; the twin
magnets of chaos and self-organization shape the constant interplay of those factors. The human mind is
highly capable of dual processing; in fact, the continuous and virtually seamless integration of reason to
test intuition and of intuition to generate the creative thinking that fuels rational inquiry is what advances
insight and knowledge.
We usually represent problems in a linear fashion despite the convincing evidence that this type of
modeling is not appropriate or adequate for studying the nervous system or human behavior.273, 274 This
naturally leads to some interesting conclusions about the interrelationship of brain and mind when
faced with decision making in a sea of uncertainty.275, 276, 277, 278, 279 The mind is an adaptive toolbox with
genetically, culturally, and individually created and transmitted rules of thumb. These rules of thumb are
called heuristics and are foundational to daily function, intuition, or inspiration.280 The study of judgment under
uncertainty is the study of heuristics. The human species’ response to uncertainty is to rely upon experience,
coupled with knowledge, data, and applied wisdom through processes such as heuristics and insight.
xivIn their 2008 review of the progress in EBM, VM Montori and GH Guyatt reiterate a basic principle of EBM cited earlier
in this chapter: “Evidence-based medicine de-emphasizes intuition, unsystematic clinical experience, and pathophysiologic rationale (italics
added) as sufcient grounds for clinical decision making and stresses the examination of evidence from clinical research,”
ignoring the signicant push back from the international scientic and clinical community regarding the hobbling effects of
EBM on both research and translational medicine.
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Heuristics and “rules of thumb” are synonymous terms. It is important to distinguish between heuristic
and analytic thinking. For instance, heuristic thinking is indispensable for discovering a mathematical
proof, whereas analytic thinking is necessary for checking the steps of the proof.281 A limited number of
simplifying heuristics rather than more formal and extensive algorithmic processing is the rule.282 The
classic example of a heuristic that most people have experienced is the “rule of thumb” (gaze heuristic)
used for catching a ball, as illustrated in Figure 10.
The angle of gaze is the angle between the eye and the ball, relative to the ground. For years, brain
scientists assumed that a complex process of computations was required for tasks like catching a ball. The
articial intelligence (AI) groups attempted to duplicate these tasks with robotic technologies. However,
research by the ‘heuristics’ groups showed a very different process at work.283 It turns out that a player
who uses the gaze rule does not need to measure wind, air resistance, spin, or the other complex, causal
variables. “All the relevant facts are contained in one variable: the angle of gaze. Note that a player using
the gaze heuristic is not able to compute the point at which the ball will land. Yet the heuristic leads the
player to the landing point...most elders are blithely unaware of the gaze heuristic, despite it simplicity.
Once the rationale underlying an intuitive feeling is made conscious, however, it can be taught.”284
Elwyn et al., in their well reasoned paper, “Decision analysis in patient care,”285 demonstrate the efcacy
and comprehensiveness of this methodology. Naylor summarizes in his editorial comments on their paper
(published in the Lancet):
The process of individualized decision analysis might best be viewed as a way of enhancing
communication with patients, rather than as a “black box” from which directives emerge. But
if that is the ultimate aim, it seems more useful to develop simple decision aids aimed at helping
patients and doctors share information and work through tough choices in the clinical setting.
To that end, Elwyn and colleagues call on clinicians and patients to communicate better while
embracing fast and frugal rules of thumb [heuristics]. In so doing they have arguably drawn their
Figure 10:
How to Catch a Fly Ball: Players rely on unconscious rules of thumb. When a ball comes in high, a player fixates his gaze
on the ball, starts running, and adjusts his speed so that the angle of the gaze remains constant.
From page 22 of the essay Rationality for Mortals, originally published in Blackwell Handbook of Judgement and Decision Making. Copyright Oxford University Press. UK Blackwell permission pending.
21st Century Medicine | 55
readers full circle—from clinical art to bedside science and back again. It is ironic, moreover, that the best
lessons in fast and frugal rules of thumb may well come from understanding the cognitive processes
of those master clinicians who consistently make superb decisions without obvious recourse to the
canon of evidence-based medicine.286 [Italics added.]
If we are to develop both a clinical methodology and a curriculum that will approximate the best
characteristics of successful clinicians, we must compare what is usually done with what could be done.
A very pertinent example of how we might transform medical care affects the primary heuristic of
contemporary medicine—the patient history and physical exam reporting structure (the H&P heuristic)—
that dominates all communication among healthcare practitioners today. We will then compare it to the
new heuristic developed by IFM to achieve a more comprehensive communication tool.
Every healthcare provider recognizes this formal construct for medical information and communication.
It both describes and dictates the process of the patient visit. The story that emerges from a clinical
encounter is typically organized around the following elements:
It is not always recognized that this construct facilitates the “fast and frugal processing” needed to
efciently collect, collate, and use patient information. The conventional H&P heuristic propels all
information headlong toward the diagnosis, with the intention of identifying and prescribing the
pharmaceutical or procedural therapy associated with that diagnosis. Each individual diagnosis is
viewed as a distinct entity unto itself—often investigated during separate ofce calls and/or by different
practitioners. There is no place in the conventional H&P heuristic to tie together multiple diagnoses into a
consistent and coherent patient narrative. There is no identication of the antecedent conditions that may
predispose the patient to the triggering of dysfunctional adaptive responses, nor of the mediators that may
perpetuate the dysfunction. Thus, patients ltered through this conventional heuristic never have a chance
the cliniciAn’s dilemmA
From Patient Encounter to the Diagnosis:
The Conventional Medical Heuristic
•Chief Complaint(CC)*
•Historyof PresentIllness(HPI)*
•PastMedicalHistory(PMH)*
•Reviewof OrganSystems(ROS)*
•MedicationandSupplementHistory*
•DietaryHistory*
•Social,Lifestyle,ExerciseHistory**
•PhysicalExamination(PE)*
•LaboratoryandImagingEvaluations*
•AssessmentandDiagnosis*
•TreatmentInterventions(usuallypharmaceuticaland/or
procedure-based)*
*=STANDARDPRACTICE
**=EXPANDEDMODEL
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to be fully heard and understood in the context of their whole life experience. Instead, their stories are
reduced to a series of diagnoses, treated by different specialists, often in isolation from one another.
The H&P heuristic was shaped by, and thus reinforces, the organ-system model of disease, with its distinct
and separate information silos, rather than a systems-medicine perspective that encourages the search for
common underlying mechanisms of, and pathways to, disease.
IFM’s functional medicine heuristic (FM heuristic) expands upon the same basic structure we are
all familiar with, but organizes the information to integrate the patient’s genetic and developmental
susceptibilities (antecedents), historical triggers, and ongoing mediators of disease. Thus, the patient’s story
emerges with greater detail, a broader context, and a different focus and ultimate goal:
The Functional Medicine Heuristic
•Chief Complaint(CC)
•Historyof PresentIllness(HPI)
•PastMedicalHistory(PMH)
— Explore antecedents, triggers, and mediators of CC, HPI, and PMH
•Reviewof OrganSystems(ROS)
— Genetic predispositions?
•MedicationandSupplementHistory
•DietaryHistory
•Social,Lifestyle,ExerciseHistory
•PhysicalExamination(PE)
•LaboratoryandImagingEvaluations:
— Immune/inammatory imbalance
— Energy imbalance/mitochondrial dysfunction
— Digestive/absorptive and microbiological imbalance
— Detoxication/biotransformation/ excretory imbalance
— Imbalance in structural, boundary, and membrane integrity
— Hormonal and neurostransmitter imbalances
— Imbalance in mind - body - spirit integration
•InitialAssessment:
— Enter data on Matrix form; look for common themes
— Review underlying mechanisms of disease
— Recapitulate patient’s story
— Organ system-based diagnosis
— Functional medicine assessment: underlying mechanisms of disease; genetic and
environmental inuences
•TreatmentPlan:
— Individualized
— Dietary, lifestyle, environmental
— Nutritional, botanical, psychosocial, energetic, spiritual
— May include pharmaceuticals and/or procedures
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As can be seen in the FM heuristic, the diagnosis is one factor among many that help the clinician
and patient explore why and how a condition was triggered and why and how the dysfunction is being
mediated. From a disciplined ltering of the patient information through the Functional Medicine Matrix
Model™ (see Chapter 5), patterns emerge that illuminate both the underlying causes of dysfunction as
well as plausible (and multiple) points of leverage where individualized treatment can create improved
function. The potential interventions reect a broader array of health vectors than just pharmaceutical
and procedural interventions because the FM heuristic elicits a pattern that helps the clinician and patient
identify where lifestyle and environmental interventions can be applied.
Because clinical reasoning is very often grounded in heuristics (simplied models that guide evaluation
and treatment at an unconscious level of awareness), we argue that to change the outcome, we must
change the model. The ability to utilize heuristics when time and information are limited and outcomes
are uncertain is a very special cognitive trait—an evolutionary breakthrough in adaptive cognition. To
understand and rene clinical reasoning and clinical practice—to ultimately improve outcome—a deeper
understanding of these adaptive skills must be understood and consciously applied.
Insight
If we are to develop an effective model for the healing partnership, we must also explore the research that
illuminates the emergence of insight as a reproducible phenomenon.xv Brain research has illuminated
very different functions of the left and right brain that explicate the objective neural correlates of a brain
that produces insight. Among the most important features of this emerging view of brain function are the
following:
Solving computational questions is primarily a left-brain function. Asking a computational
question triggers left-brain activity at the expense of right-brain function. (This has
tremendous relevance to the interactions between doctor and patient. When a patient is
interrupted with a computational question in the midst of an attempt to describe a pattern of
dysfunction, the patient’s own opportunity for insight may be lost.)
If the left hemisphere excels at denotation—storing the primary meaning of a word—
the right hemisphere deals with connotation, everything that gets left out of a dictionary
denition, such as the emotional charge in a sentence or a metaphor. Language is so complex
that the brain has to process it in two different ways at the same time. As humans, we need to
see both the forest and the trees. The right hemisphere is what helps you see the forest.287, 288
Much of the research into the adaptive unconscious (aka unconscious cognition) suggests
that pattern recognition capacity resides in the right brain, but is not specically
localized.289, 290 Solving questions requiring insight generates activity that starts in the
prefrontal cortex and eventually extends throughout the cortex and deeper structures,
the cliniciAn’s dilemmA
xv“What is insight? The term ‘insight’ is used to designate the clear and sudden understanding of how to solve a problem.
Insight is thought to arise when a solver breaks free of unwarranted assumptions, or forms novel, task-related connections
between existing concepts or skills.” (Bowden EM. New approaches to demystifying insight. TRENDS in Cognitive Sciences.
2005;9(7):322-28.)
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searching for possible experiential information that contributes to the emergence of a pattern.
It is the appearance of that pattern that sparks the “aha” or “Eureka!” experience in the
connotative language centers of the right brain.
In brief, left-brain function helps us with the denotative, computational, linear functions of life and
thought, whereas the right brain provides the connotative shadings that give depth and character and
color to meaning. Right-brain function is the source of pattern recognition and moments of insight.
The researchers in this eld have produced a robust and credible body of research about pattern
recognition from experiments that delineate and substantiate the functions of unconscious cognition (the
adaptive unconscious) that shape moments and expressions of insight.291, 292, 293 Reproducible patterns of
brain activity correlate with the experience of insight.294 The prefrontal cortex does not simply function
as an aggregator of information. Instead, like the conductor of an orchestra, brain wave activity and
energy expenditure are coordinated as if instructed by the prefrontal cortex maestro, waving its baton and
directing the players.
This is known as top-down processing, since the prefrontal cortex (the top of the brain) is directly
modulating the activity of other areas. Studies show that cells in the right hemisphere are more broadly
tuned than cells in the left hemisphere, with longer branches and more dendritic spines. As a consequence,
neurons in the right hemisphere are collecting information from a larger area of cortical space. They
are less precise but better connected. When the brain is searching for an insight, these are the cells that
are most likely to produce it. A small fold of tissue on the surface of the right hemisphere, the anterior
superior temporal gyrus (aSTG), becomes unusually active in the second before the insight. The activation
is described as sudden and intense, a surge of electricity leading to a rush of blood.295, 296
One of the unusual aspects of insight is not the revelation itself but what happens afterward. The adult
brain is an innite library of associations, a cacophony of competing ideas, and yet, as soon as the right
association appears, we know. The new thought, which is represented by that rush of gamma waves in the
right hemisphere, immediately grabs our attention. As soon as the insight happens, it seems so obvious.
People can’t believe they didn’t see it before.297, 298, 299
Insight researchers call the “aha” experience the moment of categorical insight. This moment of epiphany
registers as a new pattern of neural activity in the prefrontal cortex. The brain cells have been altered
by the breakthrough. An insight is a restructuring of information—it’s seeing the same old thing in a
completely new way. Once that restructuring occurs, you never go back.300
Insight and the Healing Partnership
“While it’s commonly assumed that the best way to solve a difcult problem is to focus, minimize
distractions, and pay attention only to the relevant details, this clenched state of mind may inhibit the sort
of creative connections that lead to sudden breakthroughs. We suppress the very type of brain activity
that we should be encouraging. Jonathan Schooler has recently demonstrated that making people focus
on the details of a visual scene, as opposed to the big picture, can signicantly disrupt the insight process.
‘It doesn’t take much to shift the brain into left-hemisphere mode,’ he said.”301 We can extrapolate that,
as clinicians, although we don’t ignore evidence, when we want insight about a patient’s condition, we
are clearly better off not turning to left-brain analysis of the most recent RCTs. And, when we want the
patient’s insight, we must learn to elicit the patient’s story (pattern) and really listen to it.
21st Century Medicine | 59
Research focused on the typical, clinical therapeutic encounter has noted that clinicians interrupt the
patient’s ow of conversation within the rst 12 to 18 seconds (or less) of the patient’s response to a
question.302, 303 This reproducible phenomenon in the conventional clinical setting makes sense if you
compare the heuristic for contemporary medicine to the functional medicine heuristic. The heuristic of
conventional medicine (rule of thumb) achieves the stated goal in an expeditious manner: clinicians use it
to identify the primary organ system domain of the presenting problem and then focus on the differential
diagnosis within that domain, marching resolutely to the nal diagnosis. This is a computational process,
without need for a partnership that can produce insight into the underlying causes and mechanisms of the
medical problem.
The functional medicine heuristic, on the other hand, requires a carefully nurtured and protected
partnership between the clinician and the patient to illuminate the underlying mechanisms of the patient’s
illness(es). The FM heuristic requires an iterative, cooperative process that yields a more complete
narrative story. From a thorough investigation of the antecedents, triggers and mediators of the patient’s
condition, emerge information and insights that can help to shape a deeper and more comprehensive
therapeutic response.
Summary
We have devoted this chapter to achieving a better understanding of an urgent problem facing clinicians
today: how to combine both science and art, evidence and insight, into an individualized, patient-centered
approach to complex, chronic disease. We do not claim to have the (sole or denitive) answer. But we do
offer a new focus for both education and practice that can be described and substantiated, taught and
practiced. We have presented ndings that suggest that the management of uncertainty—the inherent
context of clinical medicine—requires a change in the therapeutic relationship on the part of both
clinician and patient and a change in how we view and use evidence. The technical therapeutic encounter
that has characterized a great deal of patient care for the last few decades must be transformed into a
healing partnership through appropriate applications of scientic understanding, evidence from clinical
trials, and a new understanding of brain function.
The Institute for Functional Medicine’s model of comprehensive care and primary prevention for
complex, chronic illnesses (described further in Chapter 5) is grounded in both science (the Functional
Medicine Matrix Model; evidence about common underlying mechanisms and pathways of disease;
evidence about effective approaches to the environmental and lifestyle sources of disease) and art (the
healing partnership and the search for insight in the therapeutic encounter). These two cornerstones of
clinical medicine must be integrated into our teaching and practice in order to achieve what we owe to
our patients and ourselves—a more effective response to the epidemic of chronic disease. We assert that
this can be done.
the cliniciAn’s dilemmA
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21st
century
medicine:
A New Model for Medical
Education and Practice
Chapter 5
________________________________________
Functional Medicine: A 21st Century Model
of Patient Care and Medical Education
It is much more important to know what sort of a patient has a disease than what sort of a
disease a patient has. The good physician treats the disease; the great physician treats the patient
who has the disease.
—William oSleR
Treat the patient, not the diagnosis.
—the inStitute FoR Functional medicine
In this chapter, we will review the basic principles, constructs, and methodology
of functional medicine. It is not the purpose of this paper to recapitulate the
range and depth and science of functional medicine; books and monographs
covering that material in great detail are already available for the interested
clinician and for use in health professions schools. Our purpose in the rst part
of this chapter is to describe how functional medicine is organized to deliver
personalized, systems medicine and, as such, is equipped to respond to the
challenge of treating complex, chronic disease more effectively. In the second part
of the chapter, we will discuss how clinicians can be helped to re-integrate the art
and science of medicine to create a healing partnership.
Part I: What is Functional Medicine?
Functional medicine conceptualizes health and illness as part of a continuum in
which all components of the human biological system interact dynamically with
the environment. These interactions produce patterns that change over time
in individuals. To manage the complexity inherent in this approach, functional
medicine has adopted practical models for obtaining and evaluating clinical
information that leads to individualized, patient-centered therapies.
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Functional medicine encompasses a dynamic approach to assessing, preventing, and treating complex,
chronic disease. It helps clinicians identify and ameliorate dysfunctions in the physiology and biochemistry
of the human body as a primary method of improving patient health. In this model of practice, we
emphasize that chronic disease is almost always preceded by a period of declining function in one or more
of the body’s systems. Returning patients to health requires reversing (or substantially improving) the
specic dysfunctions that have contributed to the disease state. Those dysfunctions are, for each of us, the
result of lifelong interactions among our environment, our lifestyle, and our genetic predispositions. Each
patient, therefore, represents a unique, complex, and interwoven set of inuences on intrinsic functionality
that have set the stage for the development of disease or the maintenance of health.
Historically, the word “functional” has been used somewhat pejoratively in medicine. It has implied a
disability associated with either a geriatric or psychiatric problem. We suggest, however, that this is a very
limited denition of an extremely useful word. Medicine has not really produced an efcient method for
identifying and assessing changes in basic physiological processes that produce symptoms of increasing
duration, intensity, and frequency, even though we know that such alterations in function often represent
the rst signs of conditions that, at a later stage, become pathophysiologically denable diseases. If we
broaden the use of functional to encompass this view, functional medicine becomes the science and art of
detecting and reversing alterations in function that clearly move a patient toward chronic disease over
the course of a lifetime. Thus, with functional medicine, we begin to dene a model of patient care that
seeks to identify underlying chronic dysfunctions associated with altered physiological processes and to
maximize functionality at all levels of body, mind, and spirit.
One way to conceptualize where functional medicine falls in the continuum of health and health care is to
examine the functional medicine “tree.” In its approach to complex, chronic disease, functional medicine
encompasses the whole domain represented by the graphic shown in Figure 11, but rst addresses the
patient’s core clinical imbalances, fundamental physiological processes, environmental inputs, and
genetic predispositions. Diagnosis, of course, is part of the functional medicine model, but the emphasis
is on understanding and improving the functional core of the human being as the starting point for
intervention.
FunctiOnAl medicine
21st Century Medicine | 63
Organ System Diagnosis
Signs and Symptoms
Neurology
Gastroenterology
Endocrinology
Cardiology Pulmonary
Urology/Nephrology
Hepatology
Allergy
Environmental Inputs
Fundamental Clinical Imbalances
• Hormonal and Neurotransmitter Imbalances
• Redox Imbalance + Oxidative Stress + Mitochondropathy
• Detox/Biotransformation/Excretory Imbalance
• Immune imbalance
• Inflammatory Imbalance
• Digestive/Absorptive and Microbiological Imbalance
• Structural Integrity Imbalance
Mind and Spirit
Genetic Disposition
Experiences, Attitudes, Beliefs
Fundamental Physiological Imbalances
1. Communication
• outside the cell
• inside the cell
2. Bioenergetic/Energy Transformation
3. Replication/Repair/Maintenance/
Structural Integrity
4. Elimination of Waste
5. Protection/Defense
6. Transport/Circulation
Psycho-social Physical Exercise
Trauma
Diet Nutrients
Ait/Water
Xenobiotics
Micro-organisms
Radiation
Figure 11:
The Continuum of Health and Health Care
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Functional medicine clinicians focus on restoring balance to the dysfunctional systems by strengthening
the fundamental physiological processes that underlie them, and by adjusting the environmental and
lifestyle inputs that nurture or impair them. This approach leads to therapies that focus on restoring health
and function, rather than simply controlling signs and symptoms.
Principles
Seven basic principles characterize the functional medicine paradigm:
Acknowledging the biochemical individuality of each human being, based on the
concepts of genetic and environmental uniqueness
Incorporating a patient-centered rather than a disease-centered approach to treatment
Seeking a dynamic balance among the internal and external factors in a patient’s body, mind,
and spirit
Addressing the web-like interconnections of internal physiological factors
Identifying health as a positive vitality—not merely the absence of disease—and
emphasizing those factors that encourage a vigorous physiology
Promoting organ reserve as a means of enhancing the health span, not just the life span,
of each patient
Functional medicine is a science-using profession
Environmental Inputs
At the base of the medicine tree graphic are found the building blocks of life, as well as the primary
inuences on them. When we talk about inuencing gene expression, we are interested in the interaction
between environment in the broadest sense and any genetic predispositions with which a person may have
been born—including the epi genomexvi. Many environmental factors that affect genetic expression are
(or appear to be) a matter of choice (such as diet and exercise); others are very difcult for the individual
patient to alter or escape (air and water quality, toxic exposures); and still others may be the result of
unavoidable accidents (trauma, exposure to harmful microorganisms in the food supply). Some factors
that may appear modiable are heavily inuenced by the patient’s economic status—if you are poor,
for example, it may be impossible to choose more healthful food, decrease stress in the workplace and
at home, or take the time to exercise and rest properly. Existing health status is also a powerful inuence
on the patient’s ability to alter environmental input. If you have chronic pain, exercise may be extremely
difcult; if you are depressed, self-activation is a huge challenge.
xviEpigenetics—the study of how environmental factors can affect gene expression without altering the actual DNA sequence, and
how these changes can be inherited through generations.
21st Century Medicine | 65
The inuence of these inputs on the human organism is indisputable and they are often powerful agents
in the battle for health. Ignoring them in favor of the quick x of writing a prescription means the cause
of the underlying dysfunction may be obscured, but is usually not eliminated. In general terms, the
environmental inputs listed below should be considered when working to reverse dysfunction or disease
and restore health:
Diet (type and quantity of food, food preparation, calories, fats, proteins, carbohydrates)
Nutrients (both dietary and supplemental)
Air
Water
Microorganisms (and the general condition of the soil in which food is grown)
Physical exercise
Trauma
Psychosocial and spiritual factors (including family, work, community, economic status, stress,
and belief systems)
Xenobiotics
Radiation
Fundamental Physiological Processes
There are certain physiological processes that are necessary to life. These are the “upstream” processes
that can go awry and create “downstream” dysfunctions that eventually become disease entities.
Functional medicine requires that clinicians consider these in evaluating patients, so that intervention can
occur at the most fundamental level possible. They are:
1. Communication
• outside the cell
• inside the cell
2. Bioenergetics/Energy Transformation
3. Replication/Repair/Maintenance/Structural Integrity
4. Elimination of Waste
5. Protection/Defense
6. Transport/Circulation
Although these fundamental physiological processes are usually taught in the rst two years of medical
training, where they are appropriately presented as the foundation of modern, scientic patient care,
subsequent training in the clinical sciences often fails to fully integrate knowledge of the functional
mechanisms of disease with therapeutics and prevention, emphasizing instead teaching/learning based
FunctiOnAl medicine
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on organ system diagnosis.304 Focusing predominantly on organ system diagnosis without examining the
underlying physiology that produced the patient’s signs, symptoms, and disease often leads to managing
patient care by matching diagnosis to pharmacology. The job of the healthcare provider then becomes a
technical exercise in nding the drug or procedure that best ts the diagnosis (not necessarily the patient),
leading to a signicant curtailment of critical thinking pathways: “Medicine, it seems, has little regard for
a complete description of how a myriad of pathways result in any clinical state.”305
Even more important, pharmacologic treatments are often prescribed without careful consideration of
their physiological effects across all organ systems and physiological processes (and genetic variations).306
Pharmaceutical companies have exploited this weakness. Did you ever see a drug ad that urged the
practitioner to carefully consider the impact of all other drugs being taken by the patient before
prescribing a new one? The marketing of drugs to specic specialty niches, and the use of sound bite sales
pitches that suggest discrete effects, skews healthcare thinking toward this narrow, linear logic, as notably
exemplied by the COX-2 inhibitor drugs that were so wildly successful on their introduction, only to be
subsequently withdrawn or substantially narrowed in use due to collateral damage.307, 308
Core Clinical Imbalances
The functional medicine approach to assessment, both before and after diagnosis, charts a course using
different navigational assumptions. Every health condition instigates a quest for information centered on
understanding when and how the specic biological system(s) under examination spun out of control to
begin manifesting dysfunction and/or disease. Analyzing all the elements of the patient’s story, the signs
and symptoms, and the laboratory assessment through a matrix focused on functionality requires analytic
thinking and a willingness on the part of the clinician to reect deeply on underlying biochemistry and
physiology. The foundational principles of how the human organism functions—and how its systems
communicate and interact—are essential to the process of linking ideas about multifactorial causation
with the perceptible effects we call disease or dysfunction.
To assist clinicians in this process, functional medicine has adapted and organized a set of core clinical
imbalances that function as the intellectual bridge between the rich basic science literature concerning
physiological mechanisms of disease (rst two years of medical training) and the clinical studies, clinical
experience, and clinical diagnoses of the second two years of medical training. The core clinical
imbalances serve to marry the mechanisms of disease with the manifestations and diagnoses of disease.
Many common underlying pathways of disease are reected in a few basic clinical imbalances:
Immune/inammatory imbalance
Energy imbalance/mitochondrial dysfunction
Digestive/absorptive and microbiological imbalance
Detoxication/biotransformation/excretory imbalance
Imbalance in structural, boundary, and membrane integrity
Hormonal and neurotransmitter imbalances
Imbalance in mind-body-spirit integration
21st Century Medicine | 67
Using this construct, it becomes much clearer that one disease/condition may have multiple causes (i.e.,
multiple clinical imbalances), just as one fundamental imbalance may be at the root of many seemingly
disparate conditions (see Figure 12).
The most important precept to remember about functional medicine is that restoring balance—in the
patient’s environmental inputs and in the body’s fundamental physiological processes—is the key to
restoring health.
Constructing the Model
Combining the principles, environmental inputs, fundamental physiological processes, and core clinical
imbalances creates a new information-gathering-and-sorting architecture for clinical practice. This new
model includes an explicit emphasis on principles and mechanisms that weld meaning and mechanistic
explanations to the diagnosis and deepen the clinician’s understanding of the often overlapping ways
things go wrong. Any methodology for constructing a coherent story and an effective therapeutic plan
in the context of complex, chronic illness must be exible and adaptive. Like an accordion le that can
compress and expand upon demand, the amount and kind of data needed will necessarily change in
accordance with the patient’s situation and the clinician’s time and ability to piece together the underlying
threads of dysfunction. There are many pathways to illness; therefore, the accordion le must expand to
incorporate a much larger database of relevant information. For example, the Chief Complaint, History
of Present Illness, and Past Medical History sections must expand to include a thorough investigation of
antecedents, triggers, and mediators. Personalized medical care without this expanded investigation will
fall short.
Distilling the data from the expanded history, physical exam, and laboratory into a narrative story line that
includes antecedents, triggers, and mediators can be challenging. Key to developing a thorough narrative
One Condition – Many Imbalances
One Imbalance – Many Conditions
Obesity
Inflammation
Heart Disease Depression Arthritis Cancer Diabetes
Inflammation Hormones
Genetics &
Epigenetics Diet & Exercise Mood Disorders
One Condition – Many Imbalances
One Imbalance – Many Conditions
Obesity
Inflammation
Heart Disease Depression Arthritis Cancer Diabetes
Inflammation Hormones
Genetics &
Epigenetics Diet & Exercise Mood Disorders
Figure 12:
Core Clinical Imbalances—Multiple Influences
FunctiOnAl medicine
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is organizing the story according to the seven common underlying mechanisms that inuence health (the
core clinical imbalances), as shown on the Functional Medicine Matrix Model™ form (see Figure 13).
The matrix form helps organize and prioritize information, and also claries the level of present
understanding, thus illuminating where further investigation is needed. For example, indicators of
inammation on the matrix might lead the clinician to request tests for specic inammatory markers
(such as hsCRP, interleukin levels, and/or homocysteine). Essential fatty acid levels, methylation pathway
abnormalities, and organic acid metabolites help determine adequacy of dietary and nutrient intakes.
Markers of detoxication (glucuronidation and sulfation, cytochrome P450 enzyme heterogeneity) can
determine functional capacity for molecular biotransformation. Neurotransmitters and their metabolites
(vanilmandelate, homo vanillate, 5-hydroxyindoleacetate, quinolinate) and hormone cascades (gonadal
and adrenal) have obvious utility in exploring messenger molecule balance. CT scans, MRIs, or plain
x-rays extend our view of the patient’s structural dysfunctions. The use of bone scans, DEXA scans, or
bone resorption markers309, 310 can be useful in further exploring the web-like interactions of the matrix.
The Patient’s Story Retold
Antecedents
(Predisposing)
Triggering Events
(Activation)
Structural
& Membrane
Integrity
Digestion
& Absorption
Immune Surveillance
& Inflammatory Process
Psychological
& Spiritual
Equilibrium
Hormone &
Neurostrnsmitter
Regulation
Detoxification
& Biotransformation
Oxidative/Reductive
Homeodynamics
Nutrition Status Exercise Sleep Beliefs & Self Care Relationships
Date:______ Name:_________________ Age __________ Sex____ Diagnoses:__________________________________________
©2008 The Institute for Functional Medicine
Figure 13:
The Functional Medicine Matrix Model™ Form
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Newer, useful technologies such as functional MRIs, SPECT or PET scans offer more comprehensive
assessment of metabolic function within organ systems. It is the process of completing a comprehensive
history and physical and then charting these ndings on the matrix that best directs the choice of
laboratory work and successful treatment.
A completed matrix form facilitates the review of common pathways, mechanisms, and mediators of
disease, and helps clinicians select points of leverage for treatment strategies. However, even with the
matrix as an aid to synthesizing and prioritizing information, it can be very useful to consider the impact
of each variable at ve different levels:
1. Whole body (the “macro” level)
2. Organ system
3. Metabolic or cellular
4. Subcellular/mitochondrial
5. Subcellular/gene expression
Therapies should be chosen for their potential impact on the most central imbalances of the particular
patient. Evaluating interventions that are available at each of the ve levels can help to identify a
reasonably comprehensive set of options from which to choose. The following lists incorporate only a few
examples of various types of interventions within these ve different levels.
1. Whole body interventions: Because the human organism is a complex adaptive
system, with countless points of access, interventions at one level will affect points of
activity in other areas as well. For example, improving the patient’s sleep will benecially
inuence the immune response, melatonin levels, T cell lymphocyte levels, and will help to
decrease oxidative stress. Exercise reduces stress, improves insulin sensitivity, and improves
detoxication. Reducing stress (and/or improving stress management) can reduce cortisol
levels, improve sleep, improve emotional well being, and reduce the risk of heart disease.
Changing the diet can have myriad effects on health, from reducing inammation to reversing
coronary artery disease.
2. Organ system interventions: These interventions are used more frequently in the acute
presentation of illness. Examples include splinting; draining lesions; repairing lacerations;
reducing fractures, pneumothoraxes, hernias or obstructions; or removing a stone to re-
establish whole organ function. There are many interventions that improve organ function.
For example, bronchodilators improve air exchange, thereby decreasing hypoxia, reducing
oxidative stress, and improving metabolic function and oxygenation in a patient with reactive
airway disease.
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3. Metabolic or cellular interventions: Cellular health can be addressed by insuring the
adequacy of macronutrients, essential amino acids, vitamins, and cofactor minerals in the diet
(or, if necessary, from supplementation). An individual’s metabolic enzyme polymorphisms
can profoundly affect his or her nutrient requirements. For example, adding conjugated
linoleic acid (CLA) to the diet can alter the PPAR system, affect body weight, and modulate
the inammatory response.311, 312, 313 However, in a person who is diabetic or insulin resistant,
adding CLA may induce hyperproinsulinemia, which is detrimental.314, 315 Altering the types
and proportions of carbohydrates in the diet may increase insulin sensitivity, reduce insulin
secretion, and fundamentally alter metabolism in the insulin-resistant patient. Supporting
liver detoxication pathways with supplemental glycine and N-acetylcysteine improves the
endogenous production of adequate glutathione, an essential antioxidant in the central
nervous system and GI tract.
4. Subcellular/mitochondrial interventions: There are many examples of mitochondrial
nutrient support interventions.316, 317 Inadequate iron intake causes oxidants to leak from
mitochondria, damaging mitochondrial function and mitochondrial DNA. Making sure there
is sufcient iron helps alleviate this problem. Inadequate zinc intake (found in >10% of the
U.S. population) causes oxidation and DNA damage in human cells.318 Insuring the adequacy
of antioxidants and cofactors for the at-risk individual must be considered in each part of the
matrix. Carnitine, for example, is required as a carrier for the transport of fatty acids from the
cytosol into the mitochondria, improving the efciency of beta oxidation of fatty acids and
resultant ATP production. In patients who have lost signicant weight, carnitine undernutrition
can result in fatty acids undergoing omega oxidation, a far less efcient form of metabolism.319
Patients with low carnitine may also respond to riboavin supplementation. 320
5. Subcellular/gene expression interventions: Many compounds interact at the gene level
to alter cellular response, thereby affecting health and healing. Any intervention that alters
NFκB entering the nucleus, binding to DNA, and activating genes that encode inammatory
modulators such as IL-6 (and thus CRP), cyclooxygenase 2, IL-1, lipoxygenase, inducible
nitric oxide synthase, TNF-α, or a number of adhesion molecules will impact many disease
conditions.321, 322 There are many ways to alter the environmental triggers for NFκB, including
lowering oxidative stress, altering emotional stress, and consuming adequate phytonutrients,
antioxidants, alpha-lipoic acid, EPA, DHA, and GLA.323 Adequate vitamin A allows the
appropriate interaction of vitamin A-retinoic acid with over 370 genes.324 Vitamin D in its
most active form intercalates with a retinol protein and the DNA exon and modulates many
aspects of metabolism including cell division in both healthy and cancerous breast, colon,
prostate, and skin tissue.325 Vitamin D has key roles in controlling inammation, calcium
homeostasis, bone metabolism, cardiovascular and endocrine physiology, and healing.326
Experience using this model, along with improved pattern-recognition skills, will often lessen the need for
extensive laboratory assessments. There will always be, however, certain clinical conundrums that simply
cannot be assessed without objective data and, for most patients, there may be an irreducible minimum
of laboratory assessments required to accumulate information. For example, in the clinical workup of
autistic spectrum disorders in children, heavy metal exposure and toxicity may play an important role.
Heavy metal body burden cannot be sensibly assessed without laboratory studies. Another example is
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in the context of the progressive, ongoing workup. When clinical acumen and educated steps in both
assessments and therapeutic trials do not yield expected improvement, lab testing often provides rewarding
information when focused on the unexpected outcomes in the progressive workup. This is frequently
the context for focused genomic testing. In most initial workups, lab and imaging technologies can be
reserved for those complex cases where the initial interventions prove insufcient to the task of functional
explication.
Even using the functional medicine model that has been reviewed here, no single practitioner—and
no single discipline—can cover all the viable therapeutic options. Interventions will differ by training,
licensure, specialty focus, and even by beliefs and ethnic heritage. However, all healthcare disciplines
(and all medical specialties) can—to the degree allowed by their training and licensure—use a functional
medicine approach, including integrating the matrix as a basic template for organizing and coupling
knowledge and data. So, functional medicine can provide a common language and a unied model to
facilitate integrated care. Regardless of what discipline the primary care provider has been trained in,
developing a network of capable, collaborative clinicians with whom to co-manage challenging patients
and to whom referrals can be made for therapies outside the primary clinician’s own expertise will enrich
patient care and strengthen the clinician-patient relationship.
Part II: The Healing Partnership—
A Synthesis of the Art and Science of Medical Practice
We form partnerships to achieve an objective. For example, a business partnership forms to engage in
commercial transactions for nancial gain; a marriage partnership forms to build a caring, supportive
home-centered environment. A healing partnership forms to heal the patient through the integrated
application of both the art of medicine (insight driven) and the science of medicine (evidence driven). An
effective partnership requires that trust and rapport be established. Patients must feel comfortable telling
their stories and revealing intimate information and signicant events.
The characteristics of a therapeutic encounter are fundamentally different from a healing partnership, and each
emerges from specic emphases in training. In the therapeutic encounter, the relationship forms to assess
and treat a medical problem using (usually) an organ system structure, a differential diagnosis process, and
a treatment toolbox focused on pharmacology and medical procedures. The therapeutic encounter pares
down the information ow between physician and patient to the minimum needed to identify the organ
system domain of most probable dysfunction, followed by a sorting system search (the differential diagnosis
heuristic). The purpose of this relationship is to arrive at the most probable diagnosis as quickly as possible
and select an intervention based on probable efcacy. The relationship is a left brain-guided conversation
controlled by the clinician, steeped in Bayesian statistics (EBM), and characterized by algorithmic
processing and statistical thinking.327, 328
The functional medicine healing partnership forms with a related but broader purpose: to help the patient
heal by identifying the underlying mechanisms and inuences that initiated and continue to mediate the
patient’s illness(es). This type of relationship emphasizes a shared responsibility for both identifying the
causes of the patient’s condition and achieving insight about enduring solutions. The healing partnership
is critical to the delivery of personalized, systems medicine, and to manage the uncertainty (choices under risk)
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inherent in clinical practice. Here, in the healing partnership, we nd the appropriate utilization and
integration of left-brain and right-brain functions.
Germane to this discussion, Dr. Jerome Groopman—quoted previously in Chapter 4—states:
So a thinking doctor returns to language: “Tell me the story again as if I’d never heard it—what
you felt, how it happened, when it happened.”329
In language, we have the fullest expression of the integration of left- and right-brain function. Language
is so complex that the brain has to process it in different ways simultaneously—both denotatively and
connotatively. For complexity and nuance to emerge in language, we need the left brain to see the trees,
the right brain to help us see and understand the forest.330, 331
To grasp the profound importance of the healing partnership to the creation of a system of medicine
adequate to the demands of the 21st century, we need to briey address the nature of healing and its
role in the therapeutic relationship. We have noted an emerging body of research in this area.332, 333, 334 As
Louise Acheson, MD, MS, Associate Editor for the Annals of Family Practice, articulated recently in that
journal335:
It is challenging to research this ineffable process called healing…. Hsu and colleagues asked
focus groups of nurses, physicians, medical assistants, and randomly selected patients to dene
healing and describe what facilitates or impedes it.336 The groups arrived at surprisingly convergent
denitions: “Healing is a dynamic process of recovering from a trauma or illness by working
toward realistic goals, restoring function, and regaining a personal sense of balance and peace.”
They heard from diverse participants that “healing is a journey” and “relationships are essential to
healing.”
In the 20th century, contemporary medicine, traditionally considered a healing profession, evolved
away from the role of healer of the sick to that of curing disease through modern science. Research into this
transition reveals that healing was/is associated with themes of wholeness, narrative, and spirituality.
Professionals and patients alike report healing as an intensely personal, subjective experience involving
a reconciliation of meaning for an individual and a perception of wholeness. The biomedical model as
currently congured no longer encompasses these traditional characteristics for practitioners. Healing in
a holistic sense has faded from medical attention and is rarely discussed in biomedical research reports.
Contemporary medicine considers the wholeness of healing to be beyond its orthodoxy—the domain of
the nonscientic and nonmedical.337
Research into the role of healing in the medical environment has recently generated some thoughtful and
robust investigations. John Scott and his co-investigators’ research into the healing relationship found very
similar descriptions to those of Hsu’s group, mentioned above. The participants in the study338 articulated
aspects of the healing partnership as:
1. Valuing and creating a nonjudgmental emotional bond
2. Appreciating power and consciously managing clinician power in ways that would most
benet the patient
3. Abiding and displaying a commitment to caring for patients over time
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Three relational outcomes result from these processes: trust, hope, and a sense of being known. Clinician
competencies that facilitate these processes are self-condence, emotional self-management, mindfulness,
and knowledge.339 In this rich soil, the healing partnership ourishes.
The starting point for creating a healing partnership is the patient’s experience: People,
not diseases, can heal. The integration of brain science research discussed in Chapter 4—to frame
and apply right- and left-brain functions to create a mindful, insightful context—enhances the healing
partnership during the therapeutic encounter. Mindful integration of brain function is at the heart of a
healing partnership. Some of the basic steps for establishing a healing partnership include:
1. Allow patients to express, without interruption,xvii their story about why they have come to
see you. (This is an elaboration of the Chief Complaint and Present Illness.) The manner
in which the patient frames the initial complaints often presages later insight into the root
causes. Any interruption in this early stage of narrative moves the patient back into left-brain
processing and away from insight.340
2. After focusing on the main complaint, encourage the patient’s narrative regarding their
present illness(es). Clarications can be elicited by further open-ended questioning (e.g., “tell
me more about that”; “what else do you think might be going on?”). During this portion of
the interview, there is a switching back and forth between right- and left-brain functions.
• During this conversation, signs and symptoms of the present illness are distributed by the
practitioner into the Functional Medicine Matrix Model form, according to the functional
medicine heuristic sorting system described in Chapter 4.
• The parsing is determined by an assessment of probable underlying causes—based on the
robust research evidence base about common underlying mechanisms of disease—and
ongoing mediators of the disease.
3. Next, convey to the patient in the simplest terms possible that to achieve lasting solutions to
the problem(s) for which he/she has come seeking help, a few fundamental questions must
be asked and answered in order to understand the problem in the context of the patient’s
personal life. This framing of the interview process moves the endeavor from a left-brain
compilation to a narrative that encourages insight—based on complex pattern recognition—
about the root causes of the problem.
4. Explaining the structure of the next step helps the patient participate in a journey of
exploration about their illness—and their search for health. At this stage, partial control is
handed over to the patient with the statement: “Without your help, we cannot understand your medical
problem in the depth and breadth you deserve.” Leo Galland, MD originally articulated the structure
for the patient’s part of the investigation in his antecedents/triggers/mediators schema (ATM
model).341 (An excerpt from his outstanding chapter on this topic in the Textbook of Functional
Medicine is included in the Appendix.)
xviiResearch focused on the therapeutic encounter has repeatedly found that clinicians interrupt the patient’s ow of conversation
within the rst 18 seconds or less, often denying the patient an opportunity to nish. (Beckman DB, et al. The effect of
physician behavior on the collection of data. Ann Intern Med. 1984;101:692-96.)
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a) For determining antecedent conditions, the following questions are very useful:
• When was the present problem not a problem? When were you free of this
problem?
• What were the circumstances surrounding the appearance of the problem?
• Have similar problems appeared in family members?
b) For triggers, the following question is critical:
• What conditions, activities, or events seemed to initiate the problem? (Microbes
and stressful personal events are examples, but illustrate quite different categories
of triggers. Triggers by themselves are usually insufcient for disease formation, so
triggers must be viewed within the context of the antecedent conditions.)
c) Mediators of the problem are inuences that help perpetuate it.
• There can be specic mediators of diseases in the patient’s activities, lifestyle, and
environment. Many diverse factors can affect the host’s response to stressors.
• Any of the core clinical imbalances, discussed above and shown on the Functional
Medicine Matrix Model, can transform what might have been a temporary change
in homeostasis into a chronic allostatic condition.
It helps at this juncture to emphasize again that the following issues are elemental in forming a healing
partnership:
Only the patient can inform the partnership about the conditions that provided the soil from
which the problem(s) under examination emerge(s). The patient literally owns the keys to the
joint deliberation that can provide insight about the process of achieving a healing outcome.
The professional brings experience, wisdom, tools, and techniques that can be applied to the
journey of healing. The professional also works to create the context for a healing insight to
emerge.
The patient’s information, input, mindful pursuit of insight, and engagement become “the
horse before the cart.” The cart carries the clinician—the person who guides the journey
using evidence, experience, and judgment, and who contributes the potential for expert
insight.
The crux of the healing partnership is an equal investment of focus by both clinician and patient. They
work together to identify the right places to apply leverage for change. Patients must commit to engage
both their left-brain skills and their right-brain function to inform and guide the exploration to the next
steps in assessment, therapy, understanding, and insight. Clinicians must also engage both the left-brain
computational skills and the right-brain pattern-recognition functions that, when used together, can
generate insight about the patient’s story.
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Two patient case studies (presented below) provide a glimpse into a functional medicine practice and the
healing partnership that is necessary for success. The Appendix contains a form developed by IFM faculty
for enhancing the pattern-recognition process in ulcerative colitis.
Patient #1: Kikuchi syndrome in an 18 year old female—insight from the
healing partnership
Lila was an 18-year-old female transitioning from high school to college, who during
the intervening summer experienced rapid onset of unexplained fever, profound fatigue,
and lymphadenitis, especially pronounced in the cervical region. Her extended family
included physicians, one who lived locally and led the initial investigation. The differential
included lymphoma; because of the seriousness of this possible diagnosis, a biopsy of
the enlarged cervical lymph nodes was completed expeditiously. Fortunately, the biopsy
was more consistent with Kikuchi syndrome than lymphoma. The pathology of Kikuchi
is a histocytic necrotizing lymphadenitis. Her ANA was positive at 1:320, speckled.
Kikuchi syndrome is presumed to be an immune response of T cells and histiocytes to an
infectious agent, probably viral. At this point, I was asked to consult with the patient and
her parents.
The patient was articulate, intelligent (she had been accepted to Harvard), and appeared
recovered from the acute phase of her illness. Her father and mother were both present
during the consultation. Lila was asked to narrate her story. During the telling of her
story, I sorted her symptoms and signs using the FM Heuristic (Chapter 4) and the
Functional Medicine Matrix Model (discussed above). At the end of recounting of
her story, I explained to her and her parents the functional medicine sorting system,
postulating that what we now knew from the history, lab results, and the biopsy was that
Lila’s immune system had probably been activated by a triggering agent (e.g., microbe,
toxicant). I explained that our job now required forming a partnership, using Lila’s and
her parents’ experiences through this episode of illness and my experience with immune-
mediated illnesses to build a hypothetical story together.
I further explained that we would need to consider the conditions in Lila’s family and
“habits of living” history that could be antecedent to her illness. I explained that we
would then move to the possible triggers in her recent past that might be causal or
correlative in the acute expression of her illness. I explained that once an acceptable
model emerged from our joint inquiry into the antecedents and triggers of her present
illness, we would evaluate the possible probes that might elicit further information or
generate treatment plans. They agreed to work together with me using this partnering
model.
They were not aware of any exceptional family history of autoimmune or other immune
dys-regulatory illnesses. The family’s lifestyle, including eating and exercise habits, was
laudable. We next addressed the issues of triggers. We knew from reading research sources
on Kikuchi syndrome that the most common cause of the lymphadenitis associated with
the syndrome was a microbe trigger. The parents were hopeful that we could perform lab
analyses for a host of potential viral agents. Lila interrupted her parents at this point to
advocate for quite a different possible cause.
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Lila recounted that she had been seen in the regional dermatologic referral center for her
worsening acne vulgaris. The treatment recommended by the consulting dermatologist was
a sulfa-containing antibiotic. Before coming for consultation in my clinic, Lila had posited
to her dermatologist and her primary care physician that her lymphadenitis was an
adverse drug reaction. She and her parents had been told that the severity of her illness,
if caused by a drug reaction, would necessarily be accompanied by a rash; she, however,
was absent a rash. She had been advised to continue her antibiotic. Her parents retreated
from this inquiry in the face of the authoritative disclaimer by both the specialist and the
family doctor.
However, Lila did not retreat from her insight. We discussed her intuition (insight) and
her reasoning. On the basis of her hypothesis, we jointly nalized a plan that included
abstinence from her antibiotic. I advised against a planned back-packing trip to Mexico
because of possible toxicant exposures in that environment that might confound her
clinical story. We chose to call this a therapeutic probe with my added advice regarding
follow-up. (We planned a low allergy diet and detoxication program IF the simple step
of removing the triggering agent proved to be an insufcient intervention.)
That evening, I received an email from Lila with the following graph of her illness:
Outcome: Lila has been asymptomatic following continued abstinence from the sulfa-
containing antibiotic. She has started her rst semester at Harvard. The student health
center physician became very interested in her story and has provided regular follow up,
including lab. Her ANA titer has slowly returned to normal. No further interventions have
been required. She has sought non-pharmacologic treatment interventions for her acne.
10.00
8.00
6.00
4.00
2.00
0.00
6/16 6/23 6/30 7/7 7/14 7/21 7/28
Began 6/16 7/7 10pm 7/12 2pm 7/21
Bumps appear 6/21
Kikuchi/Sulfa Timeline
KEY: Initiation of taking sulfa drug
Single re-initiation of sulfa drug
Stopped taking sulfa drug
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Patient #2: Ulcerative Colitis in a 45 year old female—
providing a context for insight
The next case illustrates the use of this same model: the pursuit of an antecedent and/or
initial trigger for illness (these categories often overlap considerably)—that is, we looked
for causes underneath the surface explanations for her condition. This 45-year-old female
presented at my ofce for IBS and diverticulitis with a recent history of hemicolectomy
for infectious colitis. The patient’s primary residual postsurgical complaints were diffuse
abdominal pain and loose stooling alternating with constipation. The review of her
present illness revealed a history since her mid-twenties of “gut problems” (her words),
including intermittent loose stools with alternating constipation. She had also over the
years become intolerant of a plethora of foods. As a result, she had received thorough
work-ups for food allergies and intolerances and was trying to follow a rather patchwork
diet plan in response to these previous lab evaluations. She had received imaging and
endoscopic procedures. However, she had not had follow-up colonoscopy since her
surgery. We discussed the need to do follow-up endoscopy to evaluate her present
symptoms (to rule out possible post-surgical adhesions complicating stool passage).
The conversation soon shifted into the ATM (antecedents, triggers, and mediators)
portion of the investigation. After describing the joint responsibilities for a deeper
understanding (insight) regarding her GI maladies, we moved to the questions regarding
antecedents for her condition. She denied any family history of similar GI illnesses in her
siblings. I then asked the question: “When was the present problem not a problem? That is, when
were you free of the problem and what were the circumstances of the problem’s rst appearance?”
At this point, our conversation stopped. She looked a bit ummoxed and asked to
consider the question further and more fully answer it when she next returned. At her
next appointment, she returned to the question, stating that she wanted to share an
experience that preceded her rst episode of GI irritability. She said that she had not
shared this story with any physician before in the context of the clinical workups for her
GI problems. She then told the following story:
I left home at an early age to escape my father. He sexually abused me and
my sisters. There did not seem to be any way to stop him; my mother seemed
powerless, even when she walked into an abusive episode. In desperation, I left
my sisters and my family, married and moved away.
My mother called me one afternoon, years after my leaving home. By that
time I was a mother myself, having married and started my own family. My
mother was quite upset and related that one of my sisters had arrived at her
door, confronting her with the accusation of my father’s sexual abuse of her in
childhood and the lack of protection by our mother. My mother was adamant in
her denial of knowledge of such wrongdoing by my father (my father had died in
the intervening years since my leaving home).
I was silent for a moment on the phone with my mother. I then made a choice
to placate my mother; I responded to her distress with a lie: “Mother, you know
how my sister is; she is so hysterical.”
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My response seemed to settle my mother down. However, now that you have
asked, this was the beginning of my gut problems. I stuffed that lie about our
childhood with our father deep down into my gut and my gut has not been
normal since.
Outcome: My patient’s therapy for her GI problems has been guided by both this
insight regarding the origins of her illness as well as by my professional expertise in the
area of both mind-body connections and GI physiology. Her therapeutic interventions
focused on the 4R functional medicine approach to GI dysfunctions342 and EMDR
psychotherapeutic modalities developed for PTSD343 (an approach that has emerged from
work with returning GIs from the Gulf War and the Afghanistan and Iraq conicts). She
now reports no further problems referable to her GI tract.
Our healing partnership helped elicit the insights that focused our attention on a
fundamental issue that was critical to her healing. Without the supportive, mindful context
that encouraged her insight to emerge, we would not have had the comprehensive patient
story that was necessary for resolution of her problems. In this journey together, both
left-brain computation (clinical and scientic evidence about the importance of the 4R
GI dysfunction program and EMDR therapy in the context of PTSD) and right-brain
functionality (a context for insight) were necessary.
As described in Chapter 4, insight researchers call this “aha” experience the moment of categorical insight.
The epiphany registers as a new pattern of neural activity in the prefrontal cortex. The brain cells have
been altered by the breakthrough. An insight is a restructuring of information—it’s seeing something in a
completely new way. Once that restructuring occurs, you never go back.344
Summary
At The Institute for Functional Medicine (IFM) we believe that functional medicine exemplies a systems-
oriented, personalized medicine that recognizes the common underlying mechanisms of complex and
chronic diseases that cut across multiple organ systems to shape a patient’s trajectory toward health or
disease. IFM’s model of comprehensive care and primary prevention for complex, chronic illnesses is
grounded in both science (the Functional Medicine Matrix Model™; evidence about common underlying
mechanisms and pathways of disease; evidence about effective approaches to the environmental and
lifestyle sources of disease) and art (the healing partnership and the search for insight in the therapeutic
encounter). We have shown how this approach offers both a conceptual model and pragmatic tools that
help to integrate the best of emerging models in both conventional and integrative medicine. When
practiced with an explicit emphasis on the importance of pattern-recognition and heuristic competencies
inherent to right-brain function, a healing partnership can ourish, insight can be achieved, and a broad
array of assessment and therapeutic tools can be utilized. We can produce a mindful medical practice
paradigm shift that can encompass the uniqueness of each person, deriving probabilities that are clinically
meaningful.
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As articulated in Gerd Gigerenzer’s thoughtful book, Rationality for Mortals: How People Cope with Uncertainty,
heuristic processing (right brain) and statistical thinking (left brain) are “complementary mental tools,
not mutually exclusive strategies; our minds need both.”345 Through this uniting of competencies, we
can incorporate the strengths of both science and art to craft an effective, personalized, and integrative
approach to patient care. Without both elements steadily at work, we will nd it exceptionally difcult to
address successfully the epidemic of chronic disease that is the challenge of 21st century medicine.
What’s Ahead?
Over the past few years, at least 17 of the schools with membership in the Consortium for Academic
Health Centers in Integrative Medicine (CAHCIM) have sent attendees for training with IFM. These
faculty, residents, fellows, and students have returned to their home institutions as strong advocates for
functional medicine (see Appendix for a compilation of relevant comments). They have helped to guide us
toward key decision makers and have coached us on useful strategies.
Thanks to these relationships, IFM has already initiated collaborative work on integrating functional
medicine into medical education. Two different medical school courses on functional medicine nutrition
and genomics were offered in 2008-2009, and six institutions have indicated strong interest in participating
in a pilot project program for 2009-2010. Early funding has been secured and strategies, timelines,
delivery formats (grand rounds, guest lectures, Webinars, print/online course materials), faculty training,
and other issues are now being worked out. We anticipate that these early pilot projects will involve at least
one allopathic medical school, one osteopathic medical school, a graduate nutrition program, a residency
program in family medicine, and a naturopathic medical school. In addition, at least one online elective in
functional medicine for medical students is in the planning stages.
A summary of these pilot projects and their short-term outcomes will be written up and added to this
paper as an update following the end of the 2009-2010 academic year. As we bring the current discussion
to a close, we’d like to reiterate that the ultimate goal of this entire project is to inspire system-wide
change. We look forward to a transformation in health professions education and clinical practice that will
help us conquer the 21st century challenge of chronic disease with as much efcacy as the 20th century
brought to acute care. The change is imminent, it is urgently needed, and it is entirely possible.
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88 | 21st Century Medicine
21st century medicine:
A New Model for Medical Education and Practice
About the Institute for Functional Medicine
The Institute for Functional Medicine (IFM) is a nonprot, tax-exempt 501(c)3 educational organization
that educates physicians and other healthcare practitioners in improving the assessment and management
of complex, chronic disease through the use of functional medicine. The Institute’s mission is threefold:
to develop the functional medicine knowledge base as a bridge between research (both emerging and
established) and clinical practice; to educate physicians and other healthcare providers in the basic science
and clinical applications of functional medicine; and to communicate with policy makers, practitioners,
educators, researchers, and the public to disseminate the functional medicine knowledge base more
widely. IFM has developed a model of comprehensive care and primary prevention for complex, chronic
illness that is grounded in both the science (the Functional Medicine Matrix Model™) and the art (the healing
partnership in the therapeutic encounter) of clinical medicine that is now being implemented by functional
medicine practitioners around the world.
The Institute for Functional Medicine is accredited by the Accreditation Council for Continuing Medical
Education (ACCME) to provide continuing medical education for physicians. IFM offers educational
publications and programs designed to raise the bar on clinicians’ standard of care. Programs such
as IFM’s Functional Medicine Certication Program and Applying Functional Medicine in Clinical
Practice (AFMCP) provide comprehensive clinical training for the assessment, treatment, prevention,
and management of patients with complex, chronic disease. Other programs include IFM’s Advanced
Practice Modules, online Webinars, and the annual International Symposia on functional medicine. The
Institute publishes textbooks, monographs, and other educational materials available for CME credits
and offers clinicians a Forum for the shared exploration of emerging research and clinical applications to
improve patient care and outcomes. Detailed information about the Institute, its educational activities, and
membership can be found at www.functionalmedicine.org.
Author David S. Jones, MD is the President of The Institute for Functional Medicine. He has practiced
as a family physician with emphasis in functional and integrative medicine for over 25 years. He is a
recognized expert in the areas of nutrition, lifestyle changes for optimal health, and managed care, as
well as the daily professional functions consistent with the modern specialty of Family Practice. He is the
Editor-in-Chief of the Textbook of Functional Medicine. Laurie Hofmann, MPH, is IFM’s Executive Director
and an advisor and consultant to several public healthcare and health education initiatives across the
country. Sheila Quinn is consulting author and editor of 21st Century Medicine: A New Model for Medical
Education and Practice and many other IFM publications including the Textbook of Functional Medicine.
For information on obtaining additional copies of 21st Century Medicine or to join us in IFM’s vision and
mission as a functional medicine practitioner, member, advocate, or sponsor, we invite you to visit our Web
site, www.functionalmedicine.org, call us at 800-228-0622, or write us at client_services@fxmed.com. To
contact the authors of 21st Century Medicine or to submit comments or questions on this publication, please
write to David S. Jones, MD at DavidJones@fxmed.com.
21st Century Medicine | A1
21st
century
medicine:
A New Model for Medical
Education and Practice
Appendix
Table of Contents
Page No.
Recommendations from the Future of
Family Medicine Project ............................................................. A2
Joint Principles of the Patient-Centered Medical Home ............ A5
List of Members of the Consortium of Academic
Health Centers for Integrative Medicine .................................... A8
Institute for Systems Biology ..................................................... A11
Denition of Evidence-Based Medicine ................................... A14
Information about the Chronic Care Model ............................ A18
Excerpts from Chapter 8, Textbook of Functional Medicine .. A25
Pattern Recognition Form—Ulcerative Colitis ........................ A28
Statements from Healthcare Practitioners ............................... A36
A2 | 21st Century Medicine
21st century medicine:
A New Model for Medical Education and Practice
Recommendations from the
Future of Family Medicine Project
(http://www.futurefamilymed.org/x24878.html)
New Model of Family Medicine
Family medicine will redesign the work and workplaces of family physicians. This redesign will foster
a New Model of Care based on the concept of a relationship-centered personal medical home, which
serves as the focal point through which all individuals — regardless of age, gender, race, ethnicity, or
socioeconomic status participate in health care. In this new medical home, patients receive a basket
of services of acute, chronic, and preventive medical care services that are accessible, accountable,
comprehensive, integrated, patient-centered, safe, scientically valid, and satisfying to both patients and
their physicians. This New Model will include technologies that enhance diagnosis and treatment for a
large portion of problems that people bring to their family physicians. Business plans and reimbursement
models will be developed to enable the reengineered practices of family physicians to thrive as personal
medical homes, and resources will be developed to help patients make informed decisions about choosing
a personal medical home. A nancially self-sustaining national resource will be implemented to provide
practices with ongoing support in transitioning to the New Model of Family Medicine.
Communications
A unied communications strategy will be developed to promote an awareness and understanding of the
New Model of Family Medicine and the concept of a Personal Medical Home. As part of this strategy,
a new symbol for family physicians will be created, and consistent terminology will be established for the
specialty, (“family medicine” rather than “family practice” and “family physician” rather than “family
practitioner”). In addition, a system will be developed to communicate and implement best practices
within family medicine.
Electronic Health Records
Electronic health records that support the New Model of family medicine will be implemented.
The electronic health record will enhance and integrate communication, diagnosis and treatment,
measurement of processes and results, analysis of the effects of co-morbidity, recording and coding
elements of whole-person care, and promoting ongoing, healing relationships between family physicians
and their patients.
Family Medicine Education
Family medicine will oversee the training of family physicians who are committed to excellence, steeped in
the core values of the discipline, expert in providing family medicine’s basket of services within the New
Model of Family Medicine, skilled at adapting to varying patient and community needs, and prepared to
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embrace new evidence-based technologies. Family medicine education will continue to include training
in maternity care, the care of hospitalized patients, community and population health, and culturally
effective and procient care. Innovation in family medicine residency programs will be supported by the
Residency Review Committee for Family Practice through 5-10 years of curricular exibility to permit
active experimentation and ongoing critical evaluation of competency-based education, expanded
training programs and other strategies to prepare graduates for the New Model. In preparation for this
process, every family medicine residency will implement electronic health records by 2006.
Life-Long Learning
The discipline of family medicine will develop a comprehensive, life-long learning program. This
program will provide the tools for each family physician to create a continuous personal, professional,
and clinical practice assessment and improvement plan that supports a succession of career stages. This
personalized learning and professional development will include self-assessment and learning modules
directed at individual physicians and group practices that incorporate science-based knowledge into
educational interventions that foster improved patient outcomes. Family medicine residency programs
and departments will incorporate continuing professional development into their curricula and will initiate
and model the support process for life-long learning and maintenance of certication.
Enhancing the Science of Family Medicine
Participation in the generation of new knowledge will be integral to the activities of all family physicians
and will be incorporated into family medicine training. Practice-based research will be integrated into the
values, structures and processes of family medicine practices. Departments of family medicine will engage
in highly collaborative research that produces new knowledge about the origins of disease and illness,
how health is gained and lost, and how the provision of care can be improved. A national entity should
be established to lead and fund research on the health and health care of whole people. Funding for the
Agency for Healthcare Research and Quality should be increased to at least $1 billion per year.
Quality of Care
Close working partnerships will be developed between academic family medicine, community-based
family physicians and other partners in order to address the quality goals specied in the IOM’s Quality
Chasm report. Family physicians and their practice partners will have support systems to measure and
report regularly their performance on the 6 IOM aims of quality health care (safe, timely, effective,
equitable, patient-centered, and efcient). Family med residency programs will track and report regularly
the performance of their residents during their training on the 6 IOM quality measures and will modify
their training programs as necessary to improve performance.
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Role of Family Medicine in Academic Health Centers
Departments of family medicine will individually and collectively analyze their position within the
academic health center setting and will take steps to enhance their contribution to the advancement and
rejuvenation of the AHC to meet the needs of the American people. A summit of policymakers and
family medicine leaders in academia and private practice will be convened to review the role of and make
recommendations on the future of family medicine in academia.
Promoting a Sufcient Family Medicine Workforce
A comprehensive Family Medicine Career Development Program and other strategies will be
implemented to recruit and train a culturally diverse family physician workforce that meets the needs
of the evolving US population for integrated health care for whole people, families and communities.
Departments of family medicine will continue to develop, implement, disseminate and evaluate best
practices in expanding student interest in the specialty.
Leadership and Advocacy
Recommendation #10 from the Future of Family Medicine Report concerned Leadership and Advocacy.
The Strategic Initiative calls for: A Leadership Center for Family Medicine and Primary Care will be
established which will develop strategies to promote family physicians and other primary care physicians
as health policy and research leaders in their communities, in government, and in other inuential groups.
In their capacity as leaders, family physicians will convene leaders to identify and develop implementation
strategies for several major policy initiatives, including assuring that every American has access to basic
health care services. Family physicians will partner with others at the local, state and national levels to
engage patients, clinicians and payers in advocating for a redesigned system of integrated, personalized,
equitable and sustainable health care.
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Joint Principles of the Patient-Centered Medical Home
February 2007
American Academy of Family Physicians (AAFP)
American Academy of Pediatrics (AAP)
American College of Physicians (ACP)
American Osteopathic Association (AOA)
Introduction
The Patient-Centered Medical Home (PC-MH) is an approach to providing comprehensive primary care
for children, youth and adults. The PC-MH is a health care setting that facilitates partnerships between
individual patients, and their personal physicians, and when appropriate, the patient’s family. The AAP,
AAFP, ACP, and AOA, representing approximately 333,000 physicians, have developed the following joint
principles to describe the characteristics of the PC-MH.
Principles
Personal physician – each patient has an ongoing relationship with a personal physician trained to
provide rst contact, continuous and comprehensive care.
Physician directed medical practice – the personal physician leads a team of individuals at the
practice level who collectively take responsibility for the ongoing care of patients.
Whole person orientation – the personal physician is responsible for providing for all the patient’s
health care needs or taking responsibility for appropriately arranging care with other qualied
professionals. This includes care for all stages of life; acute care; chronic care; preventive services; and end
of life care.
Care is coordinated and/or integrated across all elements of the complex health care system (e.g.,
subspecialty care, hospitals, home health agencies, nursing homes) and the patient’s community (e.g.,
family, public and private community-based services). Care is facilitated by registries, information
technology, health information exchange and other means to assure that patients get the indicated care
when and where they need and want it in a culturally and linguistically appropriate manner.
Quality and safety are hallmarks of the medical home:
Practices advocate for their patients to support the attainment of optimal, patient-centered
outcomes that are dened by a care planning process driven by a compassionate, robust
partnership between physicians, patients, and the patient’s family.
Evidence-based medicine and clinical decision-support tools guide decision making
Physicians in the practice accept accountability for continuous quality improvement through
voluntary engagement in performance measurement and improvement.
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Patients actively participate in decision-making and feedback is sought to ensure patients’
expectations are being met
Information technology is utilized appropriately to support optimal patient care, performance
measurement, patient education, and enhanced communication
Practices go through a voluntary recognition process by an appropriate non-governmental
entity to demonstrate that they have the capabilities to provide patient centered services
consistent with the medical home model.
Patients and families participate in quality improvement activities at the practice level.
Enhanced access to care is available through systems such as open scheduling, expanded hours and new
options for communication between patients, their personal physician, and practice staff.
Payment appropriately recognizes the added value provided to patients who have a patient-centered
medical home. The payment structure should be based on the following framework:
It should reect the value of physician and non-physician staff patient-centered care
management work that falls outside of the face-to-face visit.
It should pay for services associated with coordination of care both within a given practice
and between consultants, ancillary providers, and community resources.
It should support adoption and use of health information technology for quality
improvement;
It should support provision of enhanced communication access such as secure e-mail and
telephone consultation;
It should recognize the value of physician work associated with remote monitoring of clinical
data using technology.
It should allow for separate fee-for-service payments for face-to-face visits. (Payments for care
management services that fall outside of the face-to-face visit, as described above, should not
result in a reduction in the payments for face-to-face visits).
It should recognize case mix differences in the patient population being treated within the
practice.
It should allow physicians to share in savings from reduced hospitalizations associated with
physician-guided care management in the ofce setting.
It should allow for additional payments for achieving measurable and continuous quality
improvements.
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Background of the Medical Home Concept
The American Academy of Pediatrics (AAP) introduced the medical home concept in 1967, initially
referring to a central location for archiving a child’s medical record. In its 2002 policy statement, the AAP
expanded the medical home concept to include these operational characteristics: accessible, continuous,
comprehensive, family-centered, coordinated, compassionate, and culturally effective care. The American
Academy of Family Physicians (AAFP) and the American College of Physicians (ACP) have since
developed their own models for improving patient care called the “medical home” (AAFP, 2004) or
“advanced medical home” (ACP, 2006).
For More Information:
American Academy of Family Physicians (http://www.futurefamilymed.org)
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List of Members of the Consortium of Academic Health
Centers for Integrative Medicine (cahcim)
United States
Arizona
University of Arizona
Program in Integrative Medicine
www.integrativemedicine.arizona.edu
California
Stanford University
Stanford Center for Integrative Medicine
http://www.stanfordhospital.com/
clinicsmedServices/
clinics/complementaryMedicine/default
University of California, Irvine
Susan Samueli Center for Integrative Medicine
www.sscim.uci.edu
University of California, Los Angeles
Collaborative Centers for Integrative Medicine
www.uclamindbody.org
University of California, San Francisco
Osher Center for Integrative Medicine
www.osher.ucsf.edu
Colorado
University of Colorado at Denver School of
Medicine
The Center for Integrative Medicine
www.uch.edu/integrativemed
Connecticut
University of Connecticut
School of Medicine
www.uchc.edu
Yale University
Integrative Medicine @ Yale
cam.yale.edu
Integrative Medicine Center at Grifn
Hospital
www.imc-grifn.org
Hawaii
University of Hawaii-Manoa
John A. Burns School of Medicine
Department of Complementary and Alternative
Medicine
www.jabsom.hawaii.edu/jabsom
Illinois
Northwestern University Feinberg School of
Medicine
Northwestern Memorial Physician’s Group Center
for Integrative Medicine
www.nmpg.com
Kansas
University of Kansas
Program in Integrative Medicine
http://integrativemed.kumc.edu/
Maryland
Johns Hopkins University
School of Medicine
Center for Complementary and Alternative
Medicine www.hopkinsmedicine.org/cam
University of Maryland
Center for Integrative Medicine
www.compmed.umm.edu
Massachusetts
Boston University School of Medicine
Program in Integrative Cross Cultural Care
www.bumc.bu.edu
Harvard Medical School
Osher Institute
www.osher.hms.harvard.edu
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University of Massachusetts
Center for Mindfulness
www.umassmed.edu/cfm/index.aspx
Michigan
University of Michigan
Integrative Medicine
www.med.umich.edu/umim
Minnesota
Mayo Clinic
Complementary and Integrative Medicine Program
www.mayoclinic.org/general-internal-medicine-
rst/cimc.html
Research
http://mayoresearch.mayo.edu/mayo/research/
cimp/
University of Minnesota
Center for Spirituality and Healing
www.csh.umn.edu
New Jersey
University of Medicine and Dentistry of
New Jersey
Institute for Complementary & Alternative
Medicine
www.umdnj.edu/icam
New Mexico
University of New Mexico
Health Science Center
hsc.unm.edu/som/c
New York
Albert Einstein College of Medicine of
Yeshiva University
Continuum Center for Health and Healing
www.healthandhealingny.org
Columbia University
Richard and Hinda Rosenthal Center for
Complementary & Alternative Medicine
www.rosenthal.hs.columbia.edu
North Carolina
Duke University
Duke Integrative Medicine
www.dukeintegrativemedicine.org
University of North Carolina at Chapel Hill
Program on Integrative Medicine
pim.med.unc.edu
Wake Forest University School of Medicine
Program for Holistic & Integrative Medicine
http://www1.wfubmc.edu/phim/
Oregon
Oregon Health and Science University
Women’s Primary Care and Integrative Medicine,
Center for Women’s Health
www.ohsu.edu/cam
www.ohsuwomenshealth.com/services/doctors/
integrative.html
Pennsylvania
Thomas Jefferson University
Jefferson Myrna Brind Center of Integrative
Medicine
jefine.jefferson.edu/jmbcim
www.jeffersonhospital.org/cim
University of Pennsylvania
CAM at Penn
www.med.upenn.edu/penncam
University of Pittsburgh
Center for Integrative Medicine
http://integrativemedicine.upmc.com
Tennessee
Vanderbilt University
Vanderbilt Center for Integrative Health
www.vcih.org
Texas
University of Texas Medical Branch
UTMB Integrative Health Care
http://cam.utmb.edu/
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Vermont
University of Vermont College of Medicine
Program in Integrative Medicine
www.med.uvm.edu/integrativemedicine
Washington
University of Washington
UW Integrative Health Program
www.uwcam.org
Washington, DC
George Washington University
Center for Integrative Medicine
www.integrativemedicinedc.com
Georgetown University
School of Medicine
http://www8.georgetown.edu/departments/
physiology/cam/index.html
http://som.georgetown.edu/
Wisconsin
University of Wisconsin-Madison
UW Integrative Medicine Program
www.uwhealth.org/integrativemed
www.fammed.wisc.edu/integrative
Canada
Alberta
University of Alberta
Complementary and Alternative Research and
Education (CARE)
www.care.ualberta.ca/
University of Calgary
Canadian Institute of Natural & Integrative
Medicine
www.cinim.org
Ontario
McMaster University
Family Practice Centre of Integrative Health and
Healing
www.fpcihh.com
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Institute for Systems Biology, Seattle, WA
From their website and used with their permission: http://www.systemsbiology.org/Intro_
to_ISB_and_Systems_Biology/Predictive_Preventive_Personalized_and_Participatory
The goal of systems biology is to fundamentally transform the practice of medicine, and ISB researchers
have taken the leadership role in catalyzing this transformation. We are developing tools and techniques,
and pursuing research that will usher in a new era of predictive, preventive, and personalized medicine.
Today’s medicine is reactive: we wait until someone is sick before administering treatment. Medicine of
the future will be predictive and preventive, examining the unique biology of an individual to assess their
probability of developing various diseases and then designing appropriate treatments, even before the
onset of a disease. Today’s medicine is also myopic: we use only a few measurements to diagnose disease
and are generally unable to make ne distinctions between individuals or between subtle variations of
the same disease. Medicine of the future will use more sophisticated measurements, as well as more
measurements overall, thereby yielding accurate health assessments for truly personalized treatments.
Improved personal measurements and personalized treatments are the keys to improving health care.
Diseases arise from either genetic abnormalities, detrimental environmental factors (poor diet, infectious
organisms, or toxins), or a combination of these. We know certain genetic patterns can make a person
unusually susceptible to factors in their environment. We also know certain defective genes will increase
the probability of an individual having certain health problems. For example, a woman with a single
copy of the mutant breast cancer 1 gene (BRCA-1) has a 70 percent chance of developing breast cancer
by the time she’s 60 years old. Unfortunately, today there is no practical way for each of us to determine
our genetic makeup and, more important, to understand the likely health consequences. However, in the
future individuals will be able to easily obtain such information, and then work closely with their health
practitioner to develop a predictive, preventive and personalized health-care program.
Prediction. The technologies and tools of systems biology will provide medical practitioners with two
exciting sources of health-related diagnostic data: By examining an individual’s complete genetic makeup,
a physician will be able to generate comprehensive predictions about the patient’s health prospects. And
by examining protein markers which naturally occur in an individual’s blood, a physician will be able to
accurately determine a person’s health status, including both the current effects of any abnormal genes
and the current reactions to any environmental toxins or infectious pathogens.
Prevention. The new approach to medicine, based on each individual’s genetic makeup, will help us
determine the probability of an individual contracting certain diseases, as well as reveal how an individual
may respond to various treatments, thereby providing guidance for developing customized therapeutic
drugs. Thus another use of the technologies and tools of systems biology will be to develop preventive
treatments for individuals, based on their potential health problems, as indicated by their genetic makeup
and current blood- protein markers.
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The goal of this new approach to medicine will be to use the most fundamental health-related
information—an individual’s genetic makeup plus current health status (as identied by blood protein
markers)—to prescribe appropriate preventive drugs. For example, given your genetic makeup, you may
have a 40% chance of developing breast cancer by age 50, but if you start taking a certain drug at age 35,
that chance could drop to 5% at age 50.
In fact, scientists at ISB are currently involved in several research programs involving blood diagnosis
of complex diseases, including type I diabetes, breast cancer, and prostate cancer. Cancer is the second
leading cause of death in the United States, with prostate cancer accounting for one third of all cancer
cases among men, and breast cancer accounting for approximately half of all cancer cases among women.
ISB scientists are currently researching protein markers which occur in blood to better identify the onset,
metastatic potential, and probable course of these cancers in individuals, with the eventual goal of
developing more effective treatments.
The common theme running through all of this research and its application to medicine—the predictive
and preventive potential of systems biology—is personalization. On average, each human differs from
another by less than one percent of their genetic makeup. But these genetic differences give rise to our
physical differences, including our potential predisposition to various diseases. So the ability to examine
each individual’s unique genetic makeup and thereby customize our approaches to medical treatment is at
the heart of this new era of predictive, preventive, personalized medicine.
As a result of this personalization, medicine will become participatory. Patients will actively participate
in personal choices about illness and well–being. Participatory medicine will require the development
of powerful new approaches for securely handling enormous amounts of personal information and for
educating both patients and their physicians.
——————————————————————————————————————————
http://www.systemsbiology.org/Systems_Biology_in_Depth/Premise_of_Systems_Biology
The true test of a good system model is successful prediction of the system’s behavior under targeted
alterations (genetic or environmental perturbations) of experimental conditions. But the very properties
that make biological systems interesting and worthwhile to study their emergent properties, robustness,
stability, modularity and adaptability to change, also make their behavior hard to predict at the molecular
level. Confounding factors include functional redundancy (i.e., a given process might be accomplished by
several different molecular mechanisms), and the stochasticity of cell populations (what is measured, e.g.,
gene expression, could be an average of a wide range of discrete responses among individual cells).
Systems biologists approach this conundrum by adopting the following principles:
1. Global approaches should be taken to data collection and analyses. Ideally, high-throughput
platforms are used to collect accurate measurements under multiple sets of well-dened
experimental conditions. Technologies for performing quantitative, multi parameter
measurements on a single sample need to be developed. To add value to the analyses of data
21st Century Medicine | A13
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obtained from multiplex technologies such as chips and panels of gene deletion mutants or
RNAi gene knockouts, global approaches will incorporate relevant ndings from curated
databases and the published literature.
2. Information derived from diverse data types should be integrated. Systems biology derives
power from the leveraging of pre-existing biochemical and cell biology knowledge with the
various interaction network models inferred from the global datasets. Even though each
source of data type might be sparse, noisy, or contain systematic errors, a meaningful pattern
among the diverse data might become apparent and further analysis made possible if the
network models are integrated.
3. Mathematical and statistical modeling is essential to the quantitative analysis of a system’s
properties. Based on a working model and relevant assumptions, computer simulations are
used to probe the probable effects of perturbations on a system’s components and interactions
in the interest of making predictions that can be validated by the collection of more data.
Thus, there is a tight integration of computer modeling with experimental design.
4. Biology should drive technology which, in turn, makes better biology possible. Invention
of novel or more sophisticated data collection, analysis and modeling tools is motivated by
the need to solve a real-world biological problem. As a paradigm case, the Human Genome
Project forced the development of high-throughput DNA sequencing methodologies. The
need to perform multiparameter measurements on single cells is currently driving the
invention of microuidic/nanotechnology devices.
5. Systems biology research should create an interactive inter-disciplinary scientic culture. For
progress to occur, experts in engineering, physics, mathematics, and computer science must
join biochemists, cell biologists, and physiologists in the effort to gure out how to obtain the
required data and develop the sophisticated computational approaches that will be needed
to make viable predictions. For scientists who have been trained primarily in one of these
disciplines, doing systems biology research involves stepping outside one’s comfort zone to
learn new concepts and methodologies. Systems biology-focused institutions accept that cross-
disciplinary training from the get-go is the best way for new investigators to embrace the eld.
6. The results of research should be freely disseminated. The Human Genome Project has
revealed the enormous benet that derives from the public release of data to the community
of researchers. While not as easy to work with as genomic sequence, available microarray
datasets, yeast two-hybrid analyses, collections of gene knockout strains and the like have
accelerated progress in systems biology research. Similarly, computational biology is facilitated
by the sharing of open-source software.
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Definition of Evidence-Based Medicine
Extracted from the Centre for Evidence-Based Medicine website;
used by permission http://www.cebm.net/index.aspx?o=1014
What is EBM?
This article is based on an editorial from the British Medical Journal on 13th January 1996 (BMJ 1996;
312: 71-2)
Brief denition:
Evidence-based medicine is the conscientious, explicit and judicious use of current best evidence in
making decisions about the care of individual patients. The practice of evidence-based medicine means
integrating individual clinical expertise with the best available external clinical evidence from systematic
research.
Expanded denition:
Evidence-Based Medicine, whose philosophical origins extend back to mid-19th century Paris and earlier,
remains a hot topic for clinicians, public health practitioners, purchasers, planners, and the public. There
are now frequent workshops in how to practice and teach it (one sponsored by this journal will be held in
London on April 24th); undergraduate [1] and post-graduate training programmes [2] are incorporating
it [3] (or pondering how to do so); British centres for evidence-based practice have been established or
planned in adult medicine, child health, surgery, pathology, pharmacotherapy, nursing, general practice,
and dentistry; the Cochrane Collaboration and the York Centre for Review and Dissemination in York are
providing systematic reviews of the effects of health care; new evidence-based practice journals are being
launched; and it has become a common topic in the lay media. But enthusiasm has been mixed with some
negative reaction [4-6]. Criticism has ranged from evidence-based medicine being old-hat to it being a
dangerous innovation, perpetrated by the arrogant to serve cost-cutters and suppress clinical freedom. As
evidence-based medicine continues to evolve and adapt, now is a useful time to rene the discussion of
what it is and what it is not.
Evidence-based medicine is the conscientious, explicit and judicious use of current best evidence in
making decisions about the care of individual patients. The practice of evidence-based medicine means
integrating individual clinical expertise with the best available external clinical evidence from systematic
research. By individual clinical expertise we mean the prociency and judgement that individual clinicians
acquire through clinical experience and clinical practice. Increased expertise is reected in many ways,
but especially in more effective and efcient diagnosis and in the more thoughtful identication and
compassionate use of individual patients’ predicaments, rights, and preferences in making clinical
decisions about their care. By best available external clinical evidence we mean clinically relevant research,
often from the basic sciences of medicine, but especially from patient centred clinical research into the
accuracy and precision of diagnostic tests (including the clinical examination), the power of prognostic
21st Century Medicine | A15
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markers, and the efcacy and safety of therapeutic, rehabilitative, and preventive regimens. External
clinical evidence both invalidates previously accepted diagnostic tests and treatments and replaces them
with new ones that are more powerful, more accurate, more efcacious, and safer.
Good doctors use both individual clinical expertise and the best available external evidence, and neither
alone is enough. Without clinical expertise, practice risks becoming tyrannised by evidence, for even
excellent external evidence may be inapplicable to or inappropriate for an individual patient. Without
current best evidence, practice risks becoming rapidly out of date, to the detriment of patients.
This description of what evidence-based medicine is helps clarify what evidence-based medicine is not.
Evidence-based medicine is neither old-hat nor impossible to practice. The argument that everyone
already is doing it falls before evidence of striking variations in both the integration of patient values into
our clinical behaviour [7] and in the rates with which clinicians provide interventions to their patients [8].
The difculties that clinicians face in keeping abreast of all the medical advances reported in primary
journals are obvious from a comparison of the time required for reading (for general medicine, enough to
examine 19 articles per day, 365 days per year [9]) with the time available (well under an hour per week by
British medical consultants, even on self-reports [10]).
The argument that evidence-based medicine can be conducted only from ivory towers and armchairs is
refuted by audits in the front lines of clinical care where at least some inpatient clinical teams in general
medicine [11], psychiatry (JR Geddes, et al, Royal College of Psychiatrists winter meeting, January 1996),
and surgery (P McCulloch, personal communication) have provided evidence-based care to the vast
majority of their patients. Such studies show that busy clinicians who devote their scarce reading time to
selective, efcient, patient-driven searching, appraisal and incorporation of the best available evidence can
practice evidence-based medicine.
Evidence-based medicine is not “cook-book” medicine. Because it requires a bottom-up approach that
integrates the best external evidence with individual clinical expertise and patient-choice, it cannot result
in slavish, cook-book approaches to individual patient care. External clinical evidence can inform, but
can never replace, individual clinical expertise, and it is this expertise that decides whether the external
evidence applies to the individual patient at all and, if so, how it should be integrated into a clinical
decision. Similarly, any external guideline must be integrated with individual clinical expertise in deciding
whether and how it matches the patient’s clinical state, predicament, and preferences, and thus whether
it should be applied. Clinicians who fear top-down cook-books will nd the advocates of evidence-based
medicine joining them at the barricades.
Evidence-based medicine is not cost-cutting medicine. Some fear that evidence-based medicine will be
hijacked by purchasers and managers to cut the costs of health care. This would not only be a misuse
of evidence-based medicine but suggests a fundamental misunderstanding of its nancial consequences.
Doctors practising evidence-based medicine will identify and apply the most efcacious interventions to
maximise the quality and quantity of life for individual patients; this may raise rather than lower the cost
of their care.
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Evidence-based medicine is not restricted to randomised trials and meta-analyses. It involves tracking
down the best external evidence with which to answer our clinical questions. To nd out about the
accuracy of a diagnostic test, we need to nd proper cross-sectional studies of patients clinically suspected
of harbouring the relevant disorder, not a randomised trial. For a question about prognosis, we need
proper follow-up studies of patients assembled at a uniform, early point in the clinical course of their
disease. And sometimes the evidence we need will come from the basic sciences such as genetics or
immunology. It is when asking questions about therapy that we should try to avoid the non-experimental
approaches, since these routinely lead to false-positive conclusions about efcacy. Because the randomised
trial, and especially the systematic review of several randomised trials, is so much more likely to inform us
and so much less likely to mislead us, it has become the “gold standard” for judging whether a treatment
does more good than harm. However, some questions about therapy do not require randomised trials
(successful interventions for otherwise fatal conditions) or cannot wait for the trials to be conducted. And if
no randomised trial has been carried out for our patient’s predicament, we follow the trail to the next best
external evidence and work from there.
Despite its ancient origins, evidence-based medicine remains a relatively young discipline whose positive
impacts are just beginning to be validated [12, 13], and it will continue to evolve. This evolution will
be enhanced as several undergraduate, post-graduate, and continuing medical education programmes
adopt and adapt it to their learners’ needs. These programmes, and their evaluation, will provide further
information and understanding about what evidence-based medicine is, and what it is not.
Authors:
David L. Sackett, Professor, NHS Research and Development Centre for Evidence-Based Medicine,
Oxford.
William M. C. Rosenberg, Clinical Tutor in Medicine, Nufeld Department of Clinical Medicine,
Oxford.
J. A. Muir Gray, Director of Research and Development, Anglia and Oxford Regional Health
Auhtority, Milton Keynes
R. Brian Haynes, Professor of Medicine and Clinical Epidemiology, McMaster University Hamilton,
Canada
W. Scott Richardson, Rochester, USA
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References:
1. British Medical Association: Report of the working party on medical education. London: British
Medical Association, 1995.
2. Standing Committee on Postgraduate Medical and Dental Education: Creating a better learning
environment in hospitals: 1.Teaching hospital doctors and dentists to teach. London: SCOPME,
1994.
3. General Medical Council: Education Committee Report. London: General Medical Council,
1994.
4. Grahame-Smith D: Evidence-based medicine: Socratic dissent. BMJ 1995;310:1126-7.
5. Evidence-based medicine, in its place (editorial). Lancet 1995;346:785.
6. Correspondence. Evidence-Based Medicine. Lancet 1995;346:1171-2.
7. Weatherall DJ: The inhumanity of medicine. BMJ 1994;308:1671-2.
8. House of Commons Health Committee. Priority setting in the NHS: purchasing. First report
sessions 1994-95. London: HMSO, 1995, (HC 134-1.)
9. Davidoff F, Haynes B, Sackett D, Smith R: Evidence-based medicine; a new journal to help
doctors identify the information they need. BMJ 1995;310:1085-6.
10. Sackett DL: Surveys of self-reported reading times of consultants in Oxford, Birmingham,
Milton-Keynes, Bristol, Leicester, and Glasgow, 1995. In Rosenberg WMC, Richardson WS,
Haynes RB, Sackett DL. Evidence-Based Medicine. London: Churchill -Livingstone (in press).
11. Ellis J, Mulligan I, Rowe J, Sackett DL: Inpatient general medicine is evidence based. Lancet
1995;346:407-10.
12. Bennett RJ, Sackett DL, Haynes RB, Neufeld VR: A controlled trial of teaching critical appraisal
of the clinical literature to medical students. JAMA 1987;257:2451-4.
13. Shin JH, Haynes RB, Johnston ME: Effect of problem-based, self-directed undergraduate
education on life-long learning. Can Med Assoc J 1993;148:969-76.
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Information about the Chronic Care Model
from www.improvingchroniccare.org
With the exception of the Chronic Care Model image, all materials and text found on our Web site may
be freely used and disseminated. No ofcial permission is needed from ICIC. Certain tools, developed by
ICIC, have a copyright attached in order for us to retain the right to distribute and make revisions to the
work.
Reprint permission is required for use of the Chronic Care Model image. Copyright is held by the
American College of Physicians (ACP), which publishes the Annals of Internal Medicine journal.
The CCM image rst appeared in its current format in the Effective Clinical Practice article Chronic
Disease Management: What Will It Take To Improve Care for Chronic Illness? published in
August/September of 1998. Used with permission.
Promoting effective change in provider groups to support evidence-based clinical and
quality improvement across a wide variety of health care settings.
There are many denitions of “chronic condition,” some more expansive than others. We characterize it
as any condition that requires ongoing adjustments by the affected person and interactions with the health
care system.
133 million people, or almost half of all Americans, live with a chronic condition. 1 That number is
projected to increase by more than one percent per year by 2030, resulting in an estimated chronically ill
population of 171 million.
Almost half of all people with chronic illness have multiple conditions. As a result, many managed care
and integrated delivery systems have taken a great interest in correcting the many deciencies in current
21st Century Medicine | A19
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management of diseases such as diabetes, heart disease, depression, asthma and others. 2, 3, 4
Those deciencies include:
Rushed practitioners not following established practice guidelines
Lack of care coordination
Lack of active follow-up to ensure the best outcomes
Patients inadequately trained to manage their illnesses
Overcoming these deciencies will require nothing less than a transformation of health care, from a system
that is essentially reactive - responding mainly when a person is sick - to one that is proactive and focused
on keeping a person as healthy as possible. (5, 6, 7) To speed the transition, Improving Chronic Illness Care
created the Chronic Care Model, which summarizes the basic elements for improving care in health systems at
the community, organization, practice and patient levels.
Model Elements
The Chronic Care Model (CCM) identies the essential elements of a health care system that encourage high-
quality chronic disease care. These elements are the community, the health system, self-management support,
delivery system design, decision support and clinical information systems. Evidence-based change concepts
under each element, in combination, foster productive interactions between informed patients who take an
active part in their care and providers with resources and expertise.
The Model can be applied to a variety of chronic illnesses, health care settings and target populations. The
bottom line is healthier patients, more satised providers, and cost savings.
Development of the Chronic Care Model
The staff at the MacColl Institute for Healthcare Innovation developed the CCM by drawing on available
literature about promising strategies for chronic illness management, and organizing that literature in a new
more accessible way. The Model was further rened during a nine-month planning project supported by
The Robert Wood Johnson Foundation, and revised based on input from a large panel of national experts.
It was then used to collect data and analyze innovative programs recommended by experts. RWJF funded
the MacColl Institute to test the Model nationally across varied health care settings, creating the national
program, “Improving Chronic Illness Care” (ICIC).
Renements to the Chronic Care Model
In 2003, ICIC and a small group of experts updated the CCM to reect advances in the eld of chronic care
both from the research literature and from the scores of health care systems that implemented the Model
in their improvement efforts. We list more specic concepts under each of the six elements. Based on more
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recent evidence, ve new themes were incorporated into the CCM:
Patient Safety (in Health System);
Cultural competency (in Delivery System Design);
Care coordination (in Health System and Clinical Information Systems)
Community policies (in Community Resources and Policies); and
Case management (in Delivery System Design).
The Model element pages have been redesigned to reect these updates. Each page describes the overall
strategy for each element, and the health system change concepts necessary to achieve improvement in
that component. The renements have been emphasized in bold typeface for ready identication.
Health System
Create a culture, organization and mechanisms that promote safe, high quality care
Visibly support improvement at all levels of the organization, beginning with the senior leader
Promote effective improvement strategies aimed at comprehensive system change
Encourage open and systematic handling of errors and quality problems to improve care
Provide incentives based on quality of care
Develop agreements that facilitate care coordination within and across organizations
A system seeking to improve chronic illness care must be motivated and prepared for change throughout
the organization. Senior leadership must identify care improvement as important work, and translate it
into clear improvement goals and policies that are addressed through application of effective improvement
strategies, including use of incentives, that encourage comprehensive system change. Effective
organizations try to prevent errors and care problems by reporting and studying mistakes and making
appropriate changes to their systems. Breakdowns in communication and care coordination can be
prevented through agreements that facilitate communication and data-sharing as patients navigate across
settings and providers.
Delivery System Design
Assure the delivery of effective, efcient clinical care and self-management support
Dene roles and distribute tasks among team members
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Use planned interactions to support evidence-based care
Provide clinical case management services for complex patients
Ensure regular follow-up by the care team
Give care that patients understand and that ts with their cultural background
Improving the health of people with chronic illness requires transforming a system that is essentially
reactive - responding mainly when a person is sick - to one that is proactive and focused on keeping a
person as healthy as possible. That requires not only determining what care is needed, but spelling out
roles and tasks for ensuring the patient gets care using structured, planned interactions. And it requires
making follow-up a part of standard procedure, so patients aren’t left on their own once they leave
the doctor’s ofce. 5,6,7 More complex patients may need more intensive management (care or case
management) for a period of time to optimize clinic care and self-management. Health literacy and
cultural sensitivity are two important emerging concepts in health care. Providers are increasingly being
called upon to respond effectively to the diverse cultural and linguistic needs of patients.
Decision Support
Promote clinical care that is consistent with scientic evidence and patient preferences
Embed evidence-based guidelines into daily clinical practice
Share evidence-based guidelines and information with patients to encourage their
participation
Use proven provider education methods
Integrate specialist expertise and primary care
Treatment decisions need to be based on explicit, proven guidelines supported by clinical research.
Guidelines should also be discussed with patients, so they can understand the principles behind their care.
Those who make treatment decisions need ongoing training to stay up-to-date on the latest evidence,
using new models of provider education that improve upon traditional continuing medical education. To
change practice, guidelines must be integrated through timely reminders, feedback, standing orders and
other methods that increase their visibility at the time that clinical decisions are made. The involvement of
supportive specialists in the primary care of more complex patients is an important educational modality.
Clinical Information Systems
Organize patient and population data to facilitate efcient and effective care
Provide timely reminders for providers and patients
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Identify relevant subpopulations for proactive care
Facilitate individual patient care planning
Share information with patients and providers to coordinate care
Monitor performance of practice team and care system
Effective chronic illness care is virtually impossible without information systems that assure ready access
to key data on individual patients as well as populations of patients. 11, 12 A comprehensive clinical
information system can enhance the care of individual patients by providing timely reminders for
needed services, with the summarized data helping to track and plan care. At the practice population
level, an information system can identify groups of patients needing additional care as well as facilitate
performance monitoring and quality improvement efforts.
Self-Management Support
Empower and prepare patients to manage their health and health care
Emphasize the patient’s central role in managing their health
Use effective self-management support strategies that include assessment, goal-setting, action
planning, problem-solving and follow-up
Organize internal and community resources to provide ongoing self-management support to
patients
All patients with chronic illness make decisions and engage in behaviors that affect their health (self-
management). Disease control and outcomes depend to a signicant degree on the effectiveness of self-
management.
Effective self-management support means more than telling patients what to do. It means acknowledging
the patients’ central role in their care, one that fosters a sense of responsibility for their own health. It
includes the use of proven programs that provide basic information, emotional support, and strategies
for living with chronic illness. Self-management support can’t begin and end with a class. Using a
collaborative approach, providers and patients work together to dene problems, set priorities, establish
goals, create treatment plans and solve problems along the way.9
The Community
Mobilize community resources to meet needs of patients
Encourage patients to participate in effective community programs
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Form partnerships with community organizations to support and develop interventions that
ll gaps in needed services
Advocate for policies to improve patient care
By looking outside of itself, the health care system can enhance care for its patients and avoid duplicating
effort. Community programs can support or expand a health system’s care for chronically ill patients,
but systems often don’t make the most of such resources. A health system might form a partnership with
a local senior center that provides exercise classes as an option for elderly patients. State departments of
health and other agencies often have a wealth of helpful material available for the asking - wallet cards
with tips for controlling diabetes, for example. National patient organizations such as the American
Diabetes Association can help by promoting self-help strategies.
Local and state health policies, insurance benets, civil rights laws for persons with disabilities, and
other health-related regulations also play a critical role in chronic illness care. Advocacy by medical
organizations on behalf of their patients can make a difference.
Footnotes
1. Partnership for Solutions: Johns Hopkins University, Baltimore, MD for the Robert Wood
Johnson Foundation (September 2004 Update). “Chronic Conditions: Making the Case for
Ongoing Care”
2. D.H. Stockwell, S. Madhavan, H. Cohen, G. Gibson and M.H. Alderman, “The determinants
of hypertension awareness, treatment, and control in an insured population”, American
Journal of Public Health 84 (1994): 1768-1774
3. S.J. Kenny et al., “Survey of physician practice behaviors related to diabetes mellitus in the
U.S.: Physician adherence to consensus recommendations”, Diabetes Care 16 (1993): 1507-
1510
4. J.M. Perrin, Homer CJ, Berwick DM, Woolf AD, Freeman JL, Wennberg JE. “Variations in
rates of hospitalization of children in three urban communities”, New England Journal of
Medicine 320: 1183-1187
5. E.H. Wagner, B.T. Austin and M. Von Korff, “Improving outcomes in chronic illness”,
Managed Care Quarterly 4 (1996): (2) 12-25
6. E.H. Wagner, B.T. Austin and M. Von Korff, “Organizing care for patients with chronic
illness”, Milbank Quarterly 74 (1996): 511-544
7. E. Calkins, C. Boult, E.H. Wagner and J. Pacala, “New Ways to Care for Older People:
Building Systems Based on Evidence”, New York: Springer; (1999)
8. D.K. McCulloch, M.J. Price, M. Hindmarsh and E.H. Wagner, “A population-based approach
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to diabetes management in a primary care setting: early results and lessons learned”, Effective Clinical
Practice (1998):12-22
9. M. Von Korff, J. Gruman, J.K. Schaefer, S.J. Curry and E.H. Wagner, “Collaborative management of
chronic illness”, Annals of Internal Medicine 127 (1997): 1097-1102
10. W. Katon, M. Von Korff, E. Lin, E. Walker, G.E. Simon, T. Bush, P. Robinson and J. Russo,
“Collaborative management to achieve treatment guidelines”, Journal of the American Medical
Association 273 (1995): 1026-1031
11. M.R. Greenlick, “The emergence of population-based medicine”, HMO Practice 9 (1995): 120-122
12. E.H. Wagner, “Population-based management of diabetes care,” Patient Education and Counseling 16
(1995): 225-230
13. E.H. Wagner, C. Davis, J. Schaefer, M. Von Korff, B. Austin, “A survey of leading chronic disease
management programs: are they consistent with the literature?”, Managed Care Quarterly 7 (1999): (3)
56-66
14. Narayan KM, Boyle JP, Geiss LS, Saaddine JB, Thompson TJ. “Impact of Recent Increase in
Incidence on Future Diabetes Burden, U.S., 2005-2050”. Diabetes Care, 2006, 29 (9), 2114-2116
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Excerpts from Patient-Centered Care:
Antecedents, Triggers, and Mediators
Chapter 8, Textbook of Functional Medicine
By Leo Galland, MD
The goal of person-centered diagnosis is to enable healers to develop individualized treatment plans that are based
upon an understanding of the physiological, environmental, and psychosocial contexts within which each person’s
illnesses or dysfunctions occur…. you must start by eliciting all of the patient’s concerns. In actively listening to the
patient’s story, you attempt to discover the antecedents, triggers and mediators that underlie symptoms, signs,
illness behaviors, and demonstrable pathology. Functional medicine is based upon treatment that is collaborative,
exible, and focused on the control or reversal of each person’s individual antecedents, triggers and mediators,
rather than the treatment of disease entities.
It is the functional medicine practitioner’s job to know not just the ailments or their diagnoses, but the physical
and social environment in which sickness occurs, the dietary habits of the person who is sick (present diet and
pre-illness diet), his beliefs about the illness, the impact of illness on social and psychological function, factors that
aggravate or ameliorate symptoms, and factors that predispose to illness or facilitate recovery. This information is
necessary for establishing a functional treatment plan.
What modern science has taught us about the genesis of disease can be represented by three words: triggers,
mediators, and antecedents. Triggers are discrete entities or events that provoke disease or its symptoms. Microbes
are an example. The greatest scientic discovery of the 19th century was the microbial etiology of the major
epidemic diseases. Triggers are usually insufcient in and of themselves for disease formation, however. Host
response is an essential component.
Identifying the biochemical mediators that underlie host responses was the most productive eld of biomedical
research during the second half of the 20th century. Mediators, as the word implies, do not “cause” disease. They
are intermediaries that contribute to the manifestations of disease. Antecedents are factors that predispose to acute
or chronic illness. For a person who is ill, they form the illness diathesis. From the perspective of prevention, they
are risk factors. Knowledge of antecedents has provided a rational structure for the organization of preventive
medicine and public health.
Medical genomics seeks to better understand disease by identifying the phenotypic expression of disease-related
genes and their products. The application of genomic science to clinical medicine requires the integration of
antecedents (genes and the factors controlling their expression) with mediators (the downstream products of gene
activation). Mediators, triggers, and antecedents are not only key biomedical concepts, they are also important
psychosocial concepts. In person-centered diagnosis, the mediators, triggers, and antecedents for each person’s
illness form the focus of clinical investigation.
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Antecedents and the Origins of Illness
Understanding the antecedents of illness helps the physician understand the unique characteristics of
each patient as they relate to his or her current health status. Antecedents may be thought of as congenital
or developmental. The most important congenital factor is gender: women and men differ markedly in
susceptibility to many disorders. The most important developmental factor is age; what ails children is
rarely the same as what ails the elderly. Beyond these obvious factors lies a diversity as complex as the
genetic differences and separate life experiences that distinguish one person from another.
Triggers and the Provocation of Illness
A trigger is anything that initiates an acute illness or the emergence of symptoms. The distinction between
a trigger and a precipitating event is relative, not absolute; the distinction helps organize the patient’s story.
As a general rule, triggers only provoke illness as long as the person is exposed to them (or for a short while
afterward), whereas a precipitating event initiates a change in health status that persists long after the
exposure ends.
Common triggers include physical or psychic trauma, microbes, drugs, allergens, foods (or even the act
of eating or drinking), environmental toxins, temperature change, stressful life events, adverse social
interactions, and powerful memories. For some conditions, the trigger is such an essential part of our
concept of the disease that the two cannot be separated; the disease is either named after the trigger (e.g.,
“Strep throat”) or the absence of the trigger negates the diagnosis (e.g., concussion cannot occur without
head trauma). For chronic ailments like asthma, arthritis, or migraine headaches, multiple interacting
triggers may be present. All triggers, however, exert their effects through the activation of host-derived
mediators. In closed-head trauma, for example, activation of NMDA receptors, induction of nitric oxide
synthase (iNOS), and liberation of free intra-neuronal calcium determine the late effects. Intravenous
magnesium at the time of trauma attenuates severity by altering the mediator response.1,2 Sensitivity
to different triggers often varies among persons with similar ailments. A prime task of the functional
practitioner is to help patients identify important triggers for their ailments and develop strategies for
eliminating them or diminishing their virulence.
Mediators and the Formation of Illness
A mediator is anything that produces symptoms, damage to tissues of the body, or the types of
behaviors associated with being sick. Mediators vary in form and substance. They may be biochemical
(like prostanoids and cytokines), ionic (like hydrogen ions), social (like reinforcement for staying ill),
psychological (like fear), or cultural (like beliefs about the nature of illness). A list of common mediators
is presented in Table 8.1. Illness in any single person usually involves multiple interacting mediators.
Biochemical, psychosocial, and cultural mediators interact continuously in the formation of illness.
1Cernak I, Savic VJ, Kotur J, et al. Characterization of plasma magnesium concentration and oxidative stress
following graded traumatic brain injury in humans. J Neurotrauma. 2000;17(1):53-68.
2Vink R, Nimmo AJ, Cernak I. An overview of new and novel pharmacotherapies for use in traumatic brain
injury. Clin Exp Pharmacol Physiol. 2001;28(11):919-921.
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Table 8.1 Common Illness Mediators
Biochemical Hormones
Neurotransmitters
Neuropeptides
Cytokines
Free radicals
Transcription factors
Subatomic
Ions
Electrons
Electrical and magnetic elds
Cognitive/emotional
Fear of pain or loss
Feelings or personal beliefs about illness
Poor self-esteem, low perceived self-efcacy
Learned helplessness
Lack of relevant health information
Social/cultural
Reinforcement for staying sick
Behavioral conditioning
Lack of resources due to social isolation or poverty
The nature of the sick role and the doctor/patient relationship
Sample Form used by Functional Medicine Practitioners to
Enhance Pattern Recognition
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PATTERN RECOGNITION: ULCERATIVE COLITIS
Immune Surveillance Practitioner’s Notes
1nBreastfed
How long?
2nVaccinated
Adverse reactions?
3nSkin rashes
nReaction to contact with signicant redness
(dermatographia)?
4nJoint swelling, redness
5nDry mouth, lack of salivation
6nDry eyes
7nMigraines
Triggered by foods ______ odors _______
8nCravings
Fatigue after eating certain foods?
9nIllness, dysfunction after u-like or GI u illness
10 nNeurological symptoms that developed slowly over
the course of a day and then resolved after several
weeks to months, clearing slowly
n Change in vision n Coordination
n Numbness n Cognitive problems
11 nFamily history of autoimmune disease
12 nMultiple infections
13 nNon-specic increased mucus / allergic symptoms
14 nFatigue
15 nOther:
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PATTERN RECOGNITION: ULCERATIVE COLITIS
Inammatory Process Practitioner’s Notes
1nSwelling
n Diffuse (edema)
n Localized (angioedema, papules, uticaria)
2nErthema (hyperemia, rashes, erysipelas)
3nHeat
n systemic (fever) n localized (warmth)
4nPain (arthralgias, neuralgias, cramping)
5nIrritation (pruritis, sneezing, etc.)
6nLoss of function
n Associated with pain or scarring
n Cognitive impairment (neurodegeneration)
7nExcessive mucus or uid production (includes
bronchospasm, diarrhea, etc.)
8nInammatory markers
n Elevated CRP, ESR, WBC (microscopic or gross
purulence)
n thrombocytosis
n brinogen
n inammatory cytokines (IL-1, IL-6, TNF alpha),
n decreased complement split products,
n homocysteine
n lipoprotein A2 (PLAC)
n calprotectin (fecal or serum)
9nAutoantibodies (ANA, RF) or elevated
immunoglobulins (abnormal SPEP, tissue
transglutaminase IgC, etc.
10 nElevated free radical markers (lipid peroxides, F2
isoprostanes, 8-OH-d-G)
11 nHypercoagulability
12 nOther:
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PATTERN RECOGNITION: ULCERATIVE COLITIS
Digestion, Absorption, Barrier Integrity Practitioner’s Notes
1nSymptoms that arise around eating
2n
n
Chew your food thoroughly and east slowly
or
East quickly or on the run
3nProblems with saliva, such as dry mouth or
drooling?
4n
n
Experience early satiety, fullness with small portions
Consistent discomfort after eating a typical meal
5nFrequent nauseas
Triggered by:___________________________
6nGas or bloating
7nBurping, belching, gurgling, rumbling
8nDiagnosed with reux disease (GERD)?
Medication________________ x day, week
9nDiagnosed with peptic ulcers
Antacids________________ x day, week
10 nTend toward wither diarrhea (loos stools) or
constipation? If so, which is more typical?
Bowel mocements____________ x day, week
11 nStool consistency varies______________ If so,
which is more typical?
Bowel movements_________ x day / week
12 nEver sweat intensely after eating certain foods or
after meals?
13 nCamp, raft or spend time in wilderness areas and if
so, do you drink stream water?
14 nLive with pets? If so, have they had
gastrointenstinal infections?
15 nOther:
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PATTERN RECOGNITION: ULCERATIVE COLITIS
Detoxication and Biotransformation Practitioner’s Notes
1n
n
Smoke_____ how much x day / week______
Exposed regularly to secondhand smoke
2nMercury amalgam llings
3nLive or work in a densely populated area or near
an industrial plant
4n
n
Use of pesticides, herbicides, insecticides in the
home or garden
5nUse of chemical preparations at work or as hobby
6nBreathe toxic elements in the air, fumes or other
petrochemicals
7nSymptoms (fatigue, headaches, nausea) upon
exposure to various chemicals (such as perfume,
smoke, diesel or gas fumes, etc.)
8nEat sh three times a week or more
9nProne to problems taking most medications (overly
sensitive to most medication and experience
numerous side effects)
10 n
n
n
React quickly to dental anesthetics
Require repeated administraiton of anesthetic
Numbness of one shot lasts a long time
11 nOther:
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PATTERN RECOGNITION: ULCERATIVE COLITIS
Oxidative/Reductive Practitioner’s Notes
1nSmoke_____ how much x day / week______
Exposed regularly to secondhand smoke
2nHas chronic inclammatory condition or an
autoimmune disease
3nExercise intolerance
4nEasily fatigued
5nRegularly feels ‘foggy headed’ or mentally fatigued
for no apparent reason
6nLive or work in a densely populated area or near
an industrial plant
7nUse of pesticides, herbicides, insecticides in the
home or garden
8nBreathe toxic elements in the air, fumes or other
petrochemicals
9nUnpleasant or worrisome symptoms at higher
altitudes
10 nRadiation exposure
n extensive medical radiation
n environmental exposure
11 nFly regularly
12 nOther:
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Hormone, Neurotransmitter Regulation Practitioner’s Notes
1n
n
Sluggish and unable to get started
Agitated/anxious, difculty slowing down, relax
2n
n
Difculty falling asleep
Awaken frequently during the night x ________
Typical reason for waking up_____________
3n
n
n
n
Change in metabolism, in weight or energy levels
Loss of stamina with weight gain
Increased nervousness with weight loss, or
A different combination of these problems
4n
n
More likely to be calm in a crisis
Completely disheveled and agitated even in mildly
stressful circumstances
5nTemperature intolerant:
n More often colder than others
n More often hotter than others
n Variable sensitivity to temperature
n Experience hot ashes
6nHeavy or irregular periods
7n
n
n
Loss of libido
Erectile dysfunction
Inability to achieve orgasm
8nMemory loss or brain fog
9nSigns or insulin resistance/metabolic syndrome
10 nProblems with mood or lability of emotional
responses (rapid mood swings)
11 n
n
Emotionally stable
Emotionally labile
12 nOther:
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PATTERN RECOGNITION: ULCERATIVE COLITIS
Psychological and Spiritual Equilibrium Practitioner’s Notes
1n
n
Feeling stressed
Problems with acute or chronic stress
2n
n
Sadness, depression, emotional lability, anxiety as
n current symptoms or n in the past
Mood disorders (current or past diagnosis)
3nPsychiatric diseases: thought disorders, character
disorders, neuroses (as a current symptom as well
as any history of). Symptoms as well as a formal
diagnosis.
4nAddictions (food, alcohol, drugs, cigarettes)
5nProblems with body weight (over or under) or
image: eating disorders
6nSelf destructive behavior (dened by practitioner
or patient)
7nHistory of trauma, abuse neglect
8nChronic or serious illness or pain in patient, family
or friend
9nAllergies to food/environment that create
difculties (serious issues avoiding allergens) in
living
10 nGrief, mourning, loss
11 nCaregiver for a disable, sick or elderly person
12 nFeeling unhappiness with life situation (job, family.
friends)
13 nLoss or meaning, faith
14 nLack or social support
15 nOther:
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PATTERN RECOGNITION: ULCERATIVE COLITIS
Structural Integrity Practitioner’s Notes
1nJoint pain
2nPain impacted by movement (better or worse)
3n
n
Pains that diminish as the day progresses, returning
the next AM
Pains that increase as the day progresses,
minimized the next AM
4nPains impacted by posture
5nPains impacted by repositioning the body (worse or
better)
6nPostural abnormalities (head anterior to shoulders,
swayback, tilted head, elevated shoulder, hip sway
with gait, awkward gait)
7nAbnormal wear pattern of shoes
8nAbnormal (awkward) gait patterns
9nStiffness in AM getting out of bed, relieved by a
hot shower
10 nOther:
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Statements from Healthcare Practitioners
After Experiencing Training in Functional Medicine
Michael Caruso, MD, Loma Linda University
“After the second day [of Applying Functional Medicine in Clinical Practice] I couldn’t believe that I hadn’t heard
of Functional Medicine sooner or that it isn’t taught in medical school – all the science is there!
“I think that Functional Medicine can be easily integrated in 4th year medical students PCM [Preventive
and Community Medicine] rotation as a unifying theory to the various disciplines they are exposed to. The
fundamentals of functional medicine - biochemical individuality, patient-centered medicine, the dynamic balance
of internal and external factors, web-like interconnections of physiological factors, health as a positive vitality,
and the promotion of organ reserve - can serve as a powerful pedagogical structure to bring order to a seemingly
disorderly rotation.”
Natalie Gardiner, MD, Mt. Sinai Medical Center
“Throughout the course I thought to myself that this is a way that medicine SHOULD be practiced. I believe
that FM is medicine of the 21st century.
“FM is science-based, holistic, personalized and aimed at the root of the problem and early prevention. The
noble goal of FM is to make the nation healthier. The FM approach may be time and resource consuming initially,
but the follow up visits will probably be not much longer than conventional encounters. Spending more time early
on should prevent future illnesses and save a lot of time and money.
“On the more global level FM can be an answer to the burden of chronic disease in both developed and
developing countries where it is becoming pervasive and should receive at least the same attention as ghting
AIDS for instance.”
Meg Hayes, MD, Oregon Health & Science University
“As a member of our Residency Section and as Director of the Integrative Medicine Fellowship I am involved in
curriculum development. The approaches that were introduced to me through the AFMCP [Applying Functional
Medicine in Clinical Practice] conference will be fully integrated into the curriculum of our Integrative Medicine
Fellowship, will be included as topic presentations to our students and residents, as well as taught and modeled by
me in daily preceptor relationships with learners.”
21st Century Medicine | A37
APPendiX
James Leiber, DO, Lake Erie College of Osteopathic Medicine
“We are facing a crisis in our healthcare system’s ability to alter the fundamental course of chronic diseases.
It is the way we live our lives that has resulted in the immense increase in degenerative and chronic diseases.
Understanding the impact that the world around us has on the expression of our genes is a powerful new science
that mandates a change in the way we think about disease.
“The scientic literature is abounding with information that demonstrates the need to understand and treat
patients in a comprehensive and individualized way while understanding that the body functions as a whole-
system not just isolated parts. We need clinical assessment models, diagnostic tests, new models of evidence
based research protocols, medical education curricula, and patient education initiatives that revolve around a
personalized, whole-systems approach. Chronic diseases are not just acute diseases that have gone on too long.
They are complex, multifactorial processes that develop over time via an interaction of multiple factors resulting in
multiple imbalances.
“Although all the answers are not yet available, there is certainly sufcient information right now to change the
way we are practicing and currently educating healthcare providers. Assessment and treatment strategies need
to be personalized and whole-systems based. The Functional Medicine model is a robust, exible, and scientic
approach that ties all of this information together and can be incorporated relatively comfortably into current
medical education as a new way of looking at diseases. The Institute of Functional Medicine has been doing the
footwork for this change for many years. Academic institutions now need funding help to develop pilot programs
in medical and osteopathic schools as well as for post-graduate training to assist in the educational transition to this
new model.”
Adam Perlman, MD, University of Medicine and Dentistry of New Jersey
“Overall, I see Functional Medicine as a way to re-ignite interest in primary care, allowing physicians and other
healthcare providers to truly work with patients using one of the guiding principles of Medicine, treat the cause.
It is also a part of the solution required to x our broken healthcare system. We can no longer be a system that
primarily waits for disease to happen and then treats it. We can no longer ignore the effects of environmental or
other toxins on our health. For the impact of the functional medical approach to be fully realized, much must
happen. Certainly training must be expanded into medical and allied health schools. In addition a Masters
Degree in Functional Medicine should be developed for those that want to truly focus on this type of a medical
approach. Research must be undertaken to show that the Functional Medicine approach is both effective and cost
effective for many of the chronic diseases we routinely face as healthcare providers. If training can continue to
grow, research undertaken and reimbursement changed to reward practitioners appropriately for taking the time
required to use a functional matrix approach, Functional Medicine could be the prescription that our healthcare
system needs.”
A38 | 21st Century Medicine
21st century medicine:
A New Model for Medical Education and Practice
Mark Pettus, MD, University of Massachusetts
“The content and functional-matrix model is of course, an innovative distillation of many remarkable convergent
sciences that one simply cannot access in traditional venues. … As a major afliate of The University of
Massachusetts Medical School I regularly interface with students and residents and will be introducing FM
concepts by way of lectures and clinical rotations.”
Rosa Schnyer, DAOM, University of Texas
“A series of introductory mailings I received while working at the Osher Research Center, Harvard Medical
School introduced me to Functional Medicine. The clarity of a vision grounded in biomedicine, yet in line with
my own clinical experience of many years was exciting, inspiring and impressive. The Functional Medicine
framework is not only a cohesive, effective model on its own; it also provides a dynamic system on which to
reference the scientic exploration of many traditional systems of care, such as Chinese medicine. Functional
Medicine effectively expands, for research purposes, the current biopsychosocial model to include a patient-
centered, process-focused approach to clinical care. In addition, it provides a cohesive matrix to integrate many
CAM therapies into the care of chronically ill patients.
“Functional Medicine and what I learned at AFMCP has already transformed my work in 3 very practical and
fundamental ways: 1) it has enriched the clinical care of my patients; 2) it has provided the foundation on which to
develop curricula for introductory CAM education of undergraduates in behavioral, social and medical sciences,
and graduate pharmacy students; and 3) it has offered a complex and dynamic foundation on which to develop an
integrative East-West clinical framework that I can share with my Chinese medicine colleagues.”
Leonard Smith, MD, University of Miami
“The addition of Functional Medicine will not only be cost effective, but inevitably produce better outcomes,
and help decrease the excessive mortality and morbidity we now are experiencing from chronic overuse of
pharmaceutical drugs. What’s more, Functional Medicine will also continue to gain recognition as a cornerstone
of personalized preventative medicine, which will help decrease the burden on our overtaxed medical system of
today.”
The statements made by these individuals do not necessarily reect the opinions of their
respective institutions.
