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User Manual: Excursion EX

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Farmaci generici: falsi miti e problemi reali
Achille P. Caputi
Dipartimento di Medicina Clinica e Sperimentale
Università di Messina

Disclosure
I have received consultant and speaker fees from:
• AstraZeneca, Bayer, BMS, Chiesi, DOC-generici, Eli Lilly, GFK,
Grunenthal, MSD, NovoNordisk, Otsuka, Pfizer, Rathiopharm,
Rottapharm, Sanofi-Aventis, Schering-Plough, Servier, Theva.
•Assogenerici, ANIFA, IMS
I have received grant support for investigator-initiated research
from:
•
•
•
•
•

AIFA
European Commission, FP6 and FP7 Programmes
SIMG-HSD
Roche
Novartis

Farmaco generico: definizioni
EQUIVALENTI “BRANDED”
Specialità medicinali con brevetto scaduto in possesso di un
proprio marchio distintivo (Ex originator compresi i co-marketing)
EQUIVALENTI GENERICI “UNBRANDED”
Commercializzati con la denominazione comune internazionale
(DCI) del principio attivo o la denominazione scientifica dello
stesso
EQUIVALENTI GENERICI “SEMIBRANDED”
Commercializzati con la denominazione comune internazionale
(DCI) seguita dal nome del produttore (titolare AIC)

Es. Nimesulide
Originator= 2

Generici = 16

Copie = 35

al 29.11.2012

Farmaci a brevetto scaduto
Spesa e consumo – gennaio - settembre 2012

History of the bioequivalence concept
In early 1970s, generic digoxin formulations were increasingly prescribed
in the United States, and a change in the manufacturing process of a
company in Great Britain led to an unintentional increase in the
bioavailability of one brand of digoxin tables (1,2)
Public concern and ongoing discussion about bioequivalence started with
those reports about digoxin intoxications.
It became clear that drug products that are pharmaceutically equivalent,
that is, products that contain the same drug in the same dose, are not
necessarily bioequivalent (3)

1.
2.
3.

Lindenbaum J et al., Variation in biologic availability of digoxin from four preparations. N Engl J
Med 1971; 285: 1244–47.
Schulz H-U, Steinijans VW. Striving for standards in bioequivalence assessment: a review. Int J
Clin Pharm Ther Toxicol 1991; 29: 293–8.
Skelly KP, Knapp G. Biologic activity of digoxin tablets. J Am Med Ass 1973; 224: 243.

Hatch-Waxman Act: 1984
Authorizes the FDA to approve generic drugs that were demonstrated by the manufacturer to
be bioequivalent.
The initial test-to reference ratio was 75% to 125% but was subsequently modified to 80% to
125%.
The components of this metric vary on dose administered, gut wall absorption, site of activity,
therapeutic effect, the width of the narrow therapeutic window, and the ratio of treatment
effect to drug side effects.
The definition of biologically equivalent is therefore of crucial importance and can vary based
on inert binders, manufacturer curves, area under the curve, as well as the function of time.
A prespecified equivalence of 80% to 125% might be satisfactory to meet the criteria of
equivalence if the risk– benefit ratio is wide.
For drugs with a more narrow risk– benefit ratio, that wide confidence interval would have
important implications for risk or benefit.

U.S. Food and Drug Administration. Orange Book: Approved Drug Products With Therapeutic Equivalence
Evaluations. 2011. Available at: http://www.accessdata.fda.gov/scripts/cder/ob/default.cfm. Accessed February 6,
2011.

Falsi miti: Generici e prescrizione
• I dubbi, a volte i pregiudizi, che hanno accompagnato la
loro introduzione in Italia dal 2001, fra i quali:
« … i generici sono meno efficaci … »
« … i generici sono meno sicuri … »
« … i generici causano più effetti secondari … »
« … i generici impiegano più tempo ad agire … »
« … i fabbricanti di generici non sono sottomessi
agli stessi standard di qualità … ».
Giustini SE.

My talk today
Equivalenza dei farmaci
Controlli sui farmaci e qualità dei generici
Compliance del generico verso il griffato
Sostituibilità
Indicazioni diverse fra generico e griffato
Effetto nocebo

Il Concetto di Equivalenza
Equivalenza farmaceutica
Bioequivalenza
Equivalenza terapeutica

FDA: Drug products are considered
pharmaceutical equivalents
If they contain the identical amounts of the same active ingredient in the
same dosage form and route ofadministration, as well as meet
compendia or other applicable standards of strength, quality, purity,
and identity.
However, they may differ from the innovator product in shape, drug release
mechanisms, scoring configurations, and shelf lives/expiration times.
Standards of pharmaceutical equivalence do not require that additives
such as fillers, coatings, flavoring, coloring, and binders utilized in
generic formulations be similar or identical to the innovator
counterparts.
It is important to note that some additives traditionally thought to be inert,
such as alcohol sugars, cyclodextrans, and polysorbate-80, may alter a
drug’s dissolution, thereby impacting its bioavailability.
Chen ML et al. A modern view of excipient effects on bioequivalence: case study of sorbitol. Pharm Res. 2007;24: 73–80.
Dannenfelser RM et al. Development of clinical dosage forms for a poorly water soluble drug I: application of polyethylene
glycol-polysorbate 80 solid dispersion carrier system. J Pharm Sci. 2004; 93:1165–75.
Jackson K et al. Drug-excipient interactions and their affect on absorption. Pharm Sci Technolo Today. 2000;3:336–45.

Key Terms and Definitions Related to
Therapeutic Interchange/Substitution
Pharmaceutical equivalence
Drug products that:
contain the same active ingredient(s).
are of the same dosage form and route of administration.
are identical in strength or concentration.
Bioavailability
The rate and extent to which a drug’s active ingredient is absorbed from the drug product
and becomes available at its site of action
Bioequivalence
The absence of a significant difference in bioavailability between a drug product and its
innovator when administered at the same molar dose under similar conditions in an
appropriately designed study.
Therapeutic equivalent
Drug products that are approved as safe and efficacious; are pharmaceutical equivalents; are
bioequivalent; and are manufactured in compliance with current Good Manufacturing
Practice regulations.

Peters JR et al., Generic drugs – safe, effective and affordable.
Dermatologic Therapy 2009; 22: 229-40

Farmaci generici che possono essere approvati solo
sulla base di studi di dissoluzione in vitro
• Studi di dissoluzione in vitro: informazioni su solubilità in mezzi acquosi e permeabilità
intestinale del farmaco
• Parametri valutati:
- solubilità e permeabilità del principio attivo
- similarità del profilo di dissoluzione a diversi
Linea guida OMS
valori di pH (generico vs prodotto di marca)
- eccipienti
- rischi connessi al principio attivo
(indice terapeutico, indicazioni terapeutiche)
• Quali prodotti medicinali?: formulazioni solide per uso orale, a cessione non modificata e
modificata (es. ad azione topica intestinale)

Mesalazina (800 mg, compresse)
Confronto di profili di dissoluzione

Bioequivalenza (farmacocinetica)
Sono definiti bioequivalenti due equivalenti farmaceutici le cui velocità ed
entità di assorbimento non differiscono statisticamente quando essi sono
somministrati alla stessa dose e in condizioni sperimentali simili.

Balthasar JP. American Journal of Pharmaceutical Education 1999; 63: 194-8

Come si dimostra la bioequivalenza di 2 farmaci?
Si confronta il valore medio di alcuni parametri ottenuti dalla
misurazione delle concentrazioni ematiche del farmaco in un gruppo
di volontari sani (24-36) ai quali viene somministrata in due periodi
successivi (studio cross-over) una singola dose a digiuno dei due
prodotti a confronto.

Non esistendo alcun metodo statistico
per dimostrare l’uguaglianza di due
prodotti, gli studi di bioequivalenza si
propongono di verificare l’assenza di
una differenza clinicamente rilevante
attraverso la stima di una differenza
minima ammissibile.

“essential similarity”

Requisiti per la bioequivalenza imposti dalla FDA

+20%

“L’intervallo di confidenza (*) al
90% deve ricadere nel range tra
l’80% e il 125% rispetto al prodotto
originatore…” (1)
Bioequivalente

-20%

Non bioequivalente

Range di diversità curve concentrazione/tempo
Profilo farmacocinetico dell’originatore
Profilo farmacocinetico del generico

(*)=Intervallo di confidenza al 90%= E' un intervallo di valori, calcolato
dai dati del campione, che con una certa probabilità (pari al livello di
confidenza del 90%) permette di essere nel giusto affermando che il
vero valore del parametro studiato è compreso all’interno dell’intervallo
stesso.

Tempo

(1)=Raccomandazioni del Gruppo di Studio LICE in
Merito all’Utilizzo di Prodotti Generici di Farmaci
Antiepilettici

A C max
1

T1max

C2max

Conc. Plasmatica

Giudizio di bioequivalenza

T2max

Tempo

Forme farmaceutiche
non-bioequivalenti

Forme farmaceutiche
bioequivalenti

• I valori di AUC, Cmax e Tmax devono essere simili
• E’ ammessa una variazione compresa tra 80% e 125% (ovvero:
da -20% a +25%) rispetto alla forma farmaceutica di riferimento

Pharmacokinetic parameters of test A, B and reference
R after single dose administration of metformin XR/SR
500 mg tablet in healthy male volunteers (n = 17).

Batolar LS et al., Arzneimittelforschung 2012; 62: 22–6

Summary statistics of diff erent pharmacokinetic
parameters of single dose Metformin XR/SR 500 mg
for different product in healthy human male
volunteers (n = 17).

Batolar LS et al., Arzneimittelforschung 2012; 62: 22–6

Bioequivalence (BE) testing of an acarbose formulation in healthy
volunteers through the use of recommended and innovative
pharmacodynamic (PD) parameters

FDA: 2 parameters
∆CSG,max (maximum reduction in serum glucose concentration)
AUEC (0-4h) (reduction in the AUC(0-4h) of glucose between baseline and
acarbose formulation)
4 newly defined PD measures of glucose fluctuation (glucose excursion (GE),
GE′ (glucose excursion without the effect of the homeostatic glucose control),
fAUC (degree of fluctuation of serum glucose based on AUC)),
Plateau glucose concentration (Css),
Time of maximum reduction in glucose concentration (Tmax)

AAPS Journal, 2012; 14: 345-51

Values of Parameters Used in Expanded BE Evaluation of Acarbose
Formulations in 40 Subjects with Calculated 90% CIs for T/R Values and P
Value for Tmax

AAPS Journal, 2012; 14: 345-51

Qual è l’intervallo accettabile per definire
2 prodotti bioequivalenti?
Il range di diversità che si può avere nelle
curve concentrazione/tempo in seguito
all’assunzione di due unità posologiche dello
stesso farmaco, somministrate a due
differenti soggetti è del ± 20%, ossia
compreso tra 80-125%*
*questi limiti sono asimmetrici a causa della trasformazione
logaritmica dei dati impiegati per la comparazione.

Qual è quindi la massima differenza ammessa?
Teoricamente la variazione fra un prodotto e l’altro potrebbe raggiungere il 45%, in
realtà l’obbligo di presentare un intervallo di confidenza entro i limiti stabiliti spinge i
produttori a mantenersi abbastanza vicini al 100%.

Ma è vero ?
Comparing generic and innovator drugs: a review of 12 years of bioequivalence data from the
United States Food and Drug Administration

(Davit BM et al., Ann Pharmacother 2009; 43:1583-97)

This retrospective analysis compared the generic and innovator bioequivalence measures from 2070 single-dose clinical
bioequivalence studies of orally administered generic drug products approved by the FDA from 1996 to 2007 (12 y).
Bioequivalence measures evaluated were Cmax and AUC, representing drug rate and extent of absorption, respectively.

Solo nel 2.4% (49) degli studi (2070) l’AUC del generico varia rispetto al reference
di pù del 10%.
Nessuno degli studi con tale variazione riguarda farmaci con stretto indice
terapeutico (antiepilettico, immunoppressore, ecc.)
Nell’analisi dei farmaci generici approvati in un periodo di 18 anni:
Differenza media nel fra generico e griffato:
Cmax = 4.35%
AUC = 3.56%
Differenza molto di sotto del 10% nel 98% dei casi

Qualità dei farmaci griffati e generici
Controlli della F.U. previsti per evitare difetti
durante la produzione di formulazioni farmaceutiche

• uniformità di massa;
• tempo di disaggregazione;
• velocità di dissoluzione.
massa media

deviazione %

250 mg o maggiore
oltre 80 e meno di
250 mg
80 mg o inferiore

5
7.5
10

Una domanda…..
L’AIFA controlla la qualità dei farmaci sia
griffati che generici.
Se si sospetta che l’AIFA non esegua i
controlli, perché non si dubita anche che
l’AIFA controlli realmente i farmaci griffati
e/o quelli innovativi?

Farmaci generici e compliance
Proportion of Individuals With a Medication
Possession Ratio of >80%

Discontinuation rates and health care costs in
adult patients starting generic versus brand
SSRI or SNRI antidepressants in commercial
health plans
Vlahiotis A et al. J Manag Care Pharm. 2011;17:123-32

Becky et al,. Am J Manag Care. 2009;15:450-6

MarketScan database fra il 1 luglio 2005 ed il 30 giugno
2007
Identificati tutti gli utilizzatori di antidepressivi (fra 18
e 64 anni) senza prescrizione per un SSRI/SNRI nei 180
giorni antecedenti l’inizio di una terapia SSRI/SNRI
(basiline) e seguiti per i successivi 180 giorni (follow.up)

16,659 new SSRI/SNRI users,
•47.8% (n = 7,955) initiated a brand-name medication
•52.2% (n = 8,704) initiated a generic product.
Discontinued drug within 180 days of people who initiate with
•46.8% (n = 3,723/7955) brand-name AD
•44.2% (n = 3,843/8704) generic AD .
Adjusted OR of discontinuation among generic and brand drug users = 1.09 (95% CI = 0.98-1.22)

Not significantly differ!!!!
Vlahiotis A et al. J Manag Care Pharm. 2011;17:123-32

Sostituitibilità ed equivalenza terapeutica

Warfarin
Only a few, small prospective RCT including clinical endpoints compared
generic and brand-name warfarin.
1. Alterations in INR occur after a switch in medications,
Halkin H et al. Increased warfarin doses and decreased international normalized ratio response after
nationwide generic switching. Clin Pharmacol Ther. 2003;74:215–21.

2. No consistent impact on INR after switching from brand name to
generic
Lee HL et al. Efficacy and tolerability of the switch from a branded to a generic warfarin sodium
product: an observer-blinded, randomized, crossover study. Clin Ther. 2005;27:309 –19.
Pereira JA, Holbrook AM, Dolovich L, et al. Are brand-name and generic warfarin interchangeable?
Multiple n-of-1 randomized, crossover trials. Ann Pharmacother. 2005;39:1188 –93.

3. Conversion of 87% of prescriptions to generic medication with no
changes in rates of INR testing, hospitalization for major hemorrhage,
or cerebral thromboembolismne (a large large-scale study of older
individuals in Canada)
Paterson JM, Mamdani M, Juurlink DN, et al. Clinical consequences of generic warfarin substitution:
an ecological study. JAMA. 2006;296: 1969–72

Hemorrhagic and Thrombotic Events Associated with Generic
Substitution of Warfarin in Patients with Atrial Fibrillation:
A Retrospective Analysis
Ghate SR et al., Ann Pharmacother 2011;45:701-12.
OBJECTIVE:
To assess risk of thrombotic and hemorrhagic events following substitution of
warfarin formulations in patients AF.
METHODS:
•Historical cohort analysis using a commercial insurance claims database.
•Adults with a diagnosis of AF (January 2003- December 2007), with 16 or more
months of continuous eligibility, a warfarin prescription within 30 days after
index AF diagnosis, and at least 3 warfarin prescription fills during the follow-up
period were included.
PATIENTS
37,756 subjects included in the analysis
(mean age 70.96 years, 42.3% females),
- 12,996 (34.4%) switched warfarin formulations,
- 20,292 (53.7%) used only 1 generic product,
- 4468 (11.8%) used only Coumadin during

Hazard Ratios for Adverse Events in Patients Who Switch or Remain
on Generic, Compared to Those Who Remain on Brand Warfarin

Ghate SR et al., Ann Pharmacother 2011;45:701-12

Hemorrhagic and Thrombotic Events Associated with Generic
Substitution of Warfarin in Patients with Atrial Fibrillation:
A Retrospective Analysis

Ghate SR et al., Ann Pharmacother 2011;45:701-12

Conclusions
Staying in therapy with a single generic is not associated with a
different risk of thrombotic or bleeding events compared with
staying on Coumadin,
Switching warfarin formulations, including the substitution of one
generic for another, may expose patients with AF to a higher
risk of thrombotic and bleeding events compared to remaining on
therapy with the same formulation

„Bio-Creep“
Interchangeable

Relative BA

Not Interchangeable

120
100
80
% 60

Relative BA

40
20
0

Generic 1

Innovator

Generic 2

Generic 3

Generic 4

Examples of Narrow Therapeutic Index Drugs

ACCF/AHA 2011 Health Policy Statement on Therapeutic Interchange and Substitution
A Report of the American College of Cardiology Foundation Clinical Quality Committee
Circulation 2011, 124:1290-1310.

My talk today
Equivalenza dei farmaci
Controlli sui farmaci e qualità dei generici
Efficacia clinica dei farmaci generici
Compliance del generico verso il griffato
Sostituibilità
Indicazioni diverse fra generico e griffato
Effetto nocebo

Indicazioni
Clopidogrel
Ramipril.

Le indicazioni terapeutiche dei generici sono
spesso sottodimensionate rispetto a quelle del
farmaco originatore branded
• Per ciascuna indicazione le aziende devono avviare una pratica
formale piuttosto costosa.
• Per risparmiare ne riducono il numero. E così un generico con dieci
potenziali indicazioni terapeutiche finisce per riportarne solo due
sul foglietto illustrativo.
• Ciò naturalmente confonde i medici, già portati a preferire il
farmaco di marca, ed i pazienti.
• Penalizza il mercato dei generici

Le liste di trasparenza dell’AIFA

1- Registrativa
In passato, la domanda di autorizzazione alla commercializzazione (AIC)di
un farmaco veniva presentata a livello nazionale. Per farmaci approvati
da tempo è quindi possibile un disallineamento delle indicazioni, in
quanto ogni Paese era libero di accettare o meno la dimostrazione
clinica dell’efficacia di un medicinale in una data indicazione.
Se quindi nel paese (es. Germania, Olanda, UK, ecc.), usato come
riferimento per la procedura di ottenimento dell’AIC in Italia,
l’originatore non aveva le stesse indicazioni dell’Italia, il prodotto
equivalente autorizzato in Italia veniva autorizzato per le sole indicazioni
comuni ai due paesi.
Questa situazione è comunque transitoria per due motivi:
1 l’EMA ha riconosciuto che le difformità nei testi degli stampati approvati
costituiscono un’anomalia e la direttiva 2001/83 esplicitamente prevede
un programma di armonizzazione dei testi che è già in corso e verrà
completato nei prossimi anni;
2 le richieste di AIC da parte degli originatori sono attualmente presentate
quasi esclusivamente con procedure europee (quindi con le stesse
indicazioni), pertanto i prossimi prodotti equivalenti avranno indicazioni
armonizzate.

2- Brevettuale
L’originatore ha la possibilità di ottenere la copertura brevettuale non soltanto per la
molecola ma anche per indicazioni terapeutiche specifiche. Questo fa si che ci possano
essere indicazioni con scadenze brevettuali successive a quella associata al primo brevetto
sulla molecola.
Al produttore del farmaco equivalente sarà quindi preclusa la possibilità di menzionare nel
riassunto delle caratteristiche del prodotto e nel foglio illustrativo tutte le indicazioni che
hanno una copertura brevettuale successiva a quella del primo brevetto.
Si tratta anche in questo caso di una situazione transitoria in quanto alla scadenza della
copertura brevettuale dell’indicazione , il produttore del farmaco equivalente avrà il diritto
di inserirla nel riassunto delle caratteristiche del prodotto e nel foglio illustrativo.

La “percezione” del generico
• There is an extensive publicity suggesting that
generic prescribing is potentially problematic.
• A patient knowing that a generic is being
prescribed might view this in a very negative way
and might have an increased tendency to attribute
any adverse event to the change.
• This is the “negative placebo” or “nocebo” effect,
the opposite of a placebo effect

Generic antiepileptic drugs and increased health care utilization. Fact or myth?
Besag FMC. Neurology 2010; 74: 1562-3

E per concludere…..

….. il ticket!

Copayment (ticket)
Are prescription copayments compromising patient care?
Ortiz M. Aust Prescr 2013;36:2–3
The copayment is the price paid by a patient for a prescription.
Tatchell M. Prescription pricing demystified. Aust Prescr 2009;32:6-8.

Increases in copayments primarily affect vulnerable populations such as those on
low incomes and patients with chronic medical conditions taking multiple
medications. Patients often reduce or stop taking their medicines and this can
have potentially serious health consequences.
Hynd A, Roughead EE, Preen DB, Glover J, Bulsara M, Semmens J. The impact of co-payment increases on
dispensings of government-subsidised medicines in Australia. Pharmacoepidemiol Drug Saf 2008;17:1091-9

This failure to take medicines can also lead to increased visits to the doctor and
hospitalisations.
Hsu J, Price M, Huang J, Brand R, Fung V, Hui R, et al. Unintended consequences of caps on Medicare drug benefits.
N Engl J Med 2006;354:2349-59.

There is a relationship between patient cost sharing, medication adherence and
clinical and economic outcomes. Increasing the patient’s share of medication
costs is associated with a decrease in adherence, which in turn is associated with
poorer health outcomes.
Eaddy MT, Cook CL, O’Day K, Burch SP, Cantrell CR. How patient cost-sharing trends affect adherence and
outcomes: a literature review. P T 2012;37:45-55.

Pharmacy benefits and the use of drugs by the chronically ill patients
JAMA 2004; 291: 2344-50

Politiche di contenimento del costo dei farmaci:
- aumento del ticket
- obbligo di usare i generici

Raddoppio del ticket

(Studio condotto sui farmaci di 25 industrie

farmaceutiche)

• Riduzione delle spese per farmaci dal 19 al 33%
• Riduzione spese farmaci per patologie croniche in pazienti ad
alto rischio

Doubling co-payment: results
NSAIDs 45%
antihistamines 44%.
antihyperlipidemics 34%,
antiulcerants 33%,
antiasthmatics 32%,
antihypertensives 26%,
antidepressants 26%,
antidiabetics 25%

in overall days supplied

Use of, and decrease by
antidepressants by depressed patients = 8%.
antihypertensives by hypertensive = 10%.
NSAIDs in arthritis patients = 27%
antihistamines in allergy patients = 31%.
antidiabetic = 23%.

Molti studi indicano che la sensibilità del
consumatore al cost-sharing (ticket) dipende
dalla classe terapeutica e che l’aumento del
cost sharing può ridurre l’uso di farmaci “non
essenziali” più di quello dei farmaci
essenziali”

Suboptimal statin adherence and discontinuation in secondary
prevention populations. Should we target patients with the
most to gain (J Gen Inter Med 2004;19: 638-45)

MEDICARE and drug prescription
• The “standard” Medicare Part D prescription drug benefit has a gap
in coverage after total drug costs exceed an annually adjusted
threshold, e.g., $2,510 in 2008 (1).
• During the coverage gap, beneficiaries with the standard benefit are
responsible for 100% of the cost of their medications (2).
• Studies have found that many Part D beneficiaries with a coverage
gap use less medication than prescribed due to cost and go without
necessities such as food or rent in order to afford medications (3).

1. The Medicare Prescription Drug Benefit Fact Sheet. The Henry J. Kaiser Family
Foundation (online); Available at:http://www.kff.org/medicare/upload/7044_08.pdf
2. Hsu Jet al. Unintended consequences of caps on Medicare drug benefits. N Engl J
Med. 2006; 354:2349–59.
3. Piette JD, Heisler M, Wagner TH. Problems paying out-of-pocket medication costs
among older adults with diabetes. Diabetes Care. 2004; 27:384–91.

Medicare Part D: entering the coverage gap in diabetes and
drug utilization

Beneficiaries with diabetes and other chronic diseases may be at particular risk,
given a high likelihood of entering the coverage gap due to their multi-drug
regimens.
High cost sharing among chronically ill beneficiaries has also been associated in
pre-Part D studies with a decline in health and an increase in emergency department
visits and hospitalizations.
While the majority of Part D plans provide no drug coverage during the gap, several
plans have tried to bridge the gap with coverage for generic medications only
(generic-only gap coverage).
These plans discontinue coverage for brand name medications, such as insulin,
once patients enter the gap.

Schmittdiel JA et al. Medicare Part D coverage gap and diabetes beneficiaries. Am J Manag Care. 2009; 15:189 93.
Cole JA et al. Drug copayment and adherence in chronic heart failure: effect on cost and outcomes.
Pharmacotherapy. 2006; 26:1157–64.
Heisler M et al. The health effects of restricting prescription medication use because of cost. Med Care. 2004;
42:626–34. Piette JD et al. Health insurance status, cost-related medication underuse, and outcomes among
diabetes patients in three systems of care. Med Care. 2004; 42:102–109.

Generic-only Drug Coverage in the Medicare Part D Gap and Effect on
Medication Cost-Cutting Behaviors for Patients with Diabetes: The
Translating Research into Action for Diabetes (TRIAD) Study
Duru OK et al, J Am Geriatr Soc. 2010; 58: 822–8.

Objective
To examine the association between drug coverage during the gap and medication
cost-cutting behaviors among insulin users and non-users.
Participants and Setting
2007 survey of Medicare Advantage Part D (MAPD) and Prescription Drug Plan (PDP) beneficiaries
within a network-model health system who entered the gap by October 2006 (N=1,468, 57%
response rate).
Design
The study was cross-sectional.
Measurements
The primary predictor variable was no gap coverage versus generic-only gap coverage.
Seven cost-cutting behaviors as dependent variables, including costrelated non-adherence (CRN) to
any medication were examined.
Covariates included race/ethnicity, education, health status, income, and comorbidities, as well as
generic medication use in the first quarter.

Adjusted Predicted Percentages of Medication Cost-Cutting Behaviors by
Type of Gap Coverage, amongBeneficiaries using Insulin

Generic-only Drug Coverage in the Medicare Part D Gap and Effect on Medication Cost-Cutting
Behaviors for Patients with Diabetes: The Translating Research into Action for Diabetes (TRIAD) Study
Duru OK et al, J Am Geriatr Soc. 2010; 58: 822–8.

Results
In multivariate analyses, beneficiaries taking insulin were less likely to report CRN if they
had generic-only gap coverage compared to no gap coverage (16% vs. 29%, p=0.03).
No differences in CRN by type of gap coverage were seen among beneficiaries not taking
insulin.

Conclusions
Medicare beneficiaries using insulin are at high risk of CRN.
Generic-only coverage during the gap is associated with an attenuated risk of CRN
among insulin users, possibly due to savings on other, generic medications.

Il problema generale dei generici
“Poichè di solito i farmaci generici costano meno dei farmaci branded, molte persone credono erroneamente che i
generici siano inferiori rispetto ai branded”

Doug Sporn
Director of FDA’s Office of Generic Drugs

Grazie per l’attenzione

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Presentazione_Caputi_30052013 Excursion EX 08 Caputi 30052013

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