Covance Presentation Resources Slide Template

Kurt Hutflesz Covance Inc

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PDF Session 4. Frederick Derosier Covance 
Leveraging Real-World Data in Rare Diseases: Longitudinal Data Sets as "Virtual Natural History"
Frederick Derosier, D.O. Executive Medical Director Rare Disease & Pediatrics Team Global Clinical Development, Covance Inc. Email: frederick.derosier@covance.com
·November 7, 2019
Copyright © 2019 Covance. All Rights Reserved.

Data Set Development
LabCorp Database
ICD9/10
Relevant Population Data
Set
Lab Test
Foundational Longitudinal Data Set

Supplemental Data Sources
Ex-US Pharmacy Insurers Institutions Registries Clinical Trials Chart Review

Final Population
Data
Anonymized Longitudinal Data Set

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Supplement & Expand Dataset

Longitudinal Results for a Single c.424g>a Patient
Summary of ICD-9/10 codes over time. The charts demonstrate that from 2009 to mid-2015 the patient had few unique ICD codes entered for labwork. In late 2015 ­ 2016, the pt had an increase in visit frequency and unique ICD codes associated with their tests
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Longitudinal RW Data - Individual Patient
aTTR Patient with c.424G>A
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Genotype-Phenotype Insights

Amyloidosis Cardiac ¥ Neuropathy Renal Fatigue
¥

Pathogenic, Heart1,2 n=118

Benign/VUS1,2 n=194

Benign2 n=189

¥

¥
1. http://amyloidosismutations.com/mut-attr.ph 2. https://www.ncbi.nlm.nih.gov/clinvar/variation
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Impact of I/E Criteria on Patient Pool
26% Reduction in Eligible Patients
853 Patients between 10/2010 and 10/2018 with transthyretin variant by genotyping. 801 Patients between 18 and 82 years old. 796 Without HIV, Hep B, Hep C 787 Without Malignancy, Autoimmune disease, or other neuropathy 786 Without primary amyloidosis 776 Without liver transplant 642 With creatinine < 6 mL/min/1.75 635 With Platelets < 125 x 109L 627 With ALT and AST > 1.9 ULN
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The protocol inclusion / exclusion criteria is applied to the patient pool and then matching patients are geo-
located on the map.

Longitudinal Data as a Control
Retrospective "Synthetic" Control Arm
 Integrate historical past clinical trial datasets: Covance Labs, Sponsor clinical data (EDC)
Retrospective "Contemporary" Control Arm Study using RWE
 Integrate real-world datasets, identify patients in historical RWD who meet study criteria  Outcome analysis to:
· Define an index event (e.g., start of control treatment) · Define the observation period
 Analyze outcome (incidence rates, Kaplan-Meier analysis, etc.)
Prospective "Synthetic" Control Arm Study
 Collect study data, including direct from patient through surveys, ePRO, mHealth apps  Integrate direct from patient data with EHR / Labs and other data sets for analysis
Real-World Comparative Safety Study
 Compare adverse events (AEs) rate of lab testing and clinical outcomes determined by diagnosis codes of Product X to the rate experienced by currently available products
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Real-World Evidence: Bridging the Gaps
 Unbiased by trial selection/recruitment process  Leverages multiple, existing data sources
· More robust, more rapid · Potential to unify fragmented data  Enables identification / diagnosis of target population · Characterize the patient journey  More effectively characterize genotype-phenotype  Hypothesis test  Protocol modeling

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TRANSFORMING DATA INTO INSIGHTS

Back-up
Copyright © 2019 Covance. All Rights Reserved.

"Virtual Natural Histories" ­ Longitudinal RW Datasets
Longitudinal eGFR results for c.424g>a aTTR patients
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Exploring Predictive Modeling: eGFR & Age by Mutation

eGFR Longitudinal Analysis

5

Model Based on Patients without E11.*

4

3

2

Stage Kidney Disease

GFR

1

Normal

> 90 mL/min

2

Mild CKD

= 60-89 mL/min

3

Moderate CKD = 30-59 mL/min

eGFR STAGES

1

4

Severe CKD

= 15-29 mL/min

0

30

35

40

45

50

55

60

65

70

75

80

c.337-18G>C

AGE c.76G>A

c.424G>A

c336-19G>A

5

End Stage CKD <15 mL/min

Mutation type Patient Count #

c.337-18G>C Intronic
142

c.76G>A Gly6Ser (Likely benign)
125

c.424G>A Val122lle (Pathogenic)
94

c.336-19G>A Intronic
61

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Creating a Data Lake

Identified Individuals

PHYSCIAN Survey, Chart Review,
Trial Invite

PATIENT Survey, Trial Invite

Search by ICD code/Lab Test(s)
Specialty Lab Database

Protocol Pt Consent, IRB Review

Search by ICD code/Lab Test(s)

Secure Transfer

Specialty Lab Database

De-Identification
Aggregate/Link

Secure Transfer
Compliance Check
Data Lake

Search by ICD code/Lab Test(s)
Specialty Lab Database

REPORTING NETWORK

Data Lake De-identified

End User

Data Enrichment

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Hospitals

Pharmacy

Other Data Registry Data

Development of a Dataset: Protocol Considerations

M34.0, M34.1, M34.2, M34.8, and M34.9
Plts, LFTs, Renal

Build Dataset

ICD9/10
Lab Test

Relevant Population Data Set

I/E Criteria
Age Date of Dx
Pruritis Heart Failure Arrhythmia

Targeted Dataset
Final Population Data Set

Filter Dataset

HIV/Hep B/C

Recruitment

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Patient Care Data in Rare Diseases

Delayed diagnosis Multiple physicians Uncertainty of disease progression Complexity of clinical trials Need for approved therapies
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Patient identification Identification of treating physicians
Lack of natural history data Understanding of patient perspective
De-risk clinical development

Leveraging Our Data Assets
Patient Data Privacy and Security

 Protecting the privacy and security of patient information is of paramount importance to LabCorp's business and key to maintaining trust of patients, study participants, and clients
 With respect to the use and disclosure of LabCorp patient data for clinical research purposes, our company is committed to compliance with all applicable federal, state, and local privacy laws, including HIPAA

Better Together Patients

Other LabCorp Patient Data

 Through Better Together, patients voluntarily authorize LabCorp to disclose their lab data and demographic information to Covance for the purpose of identifying and being contacted about clinical research opportunities
 Patients provide authorization through the LabCorp | PatientTM portal or such other secure means that allow for the verification of the individual's identity
 Authorization can be revoked by the patient at any time
 Covance reviews lab data for Better Together patients, and may contact patients directly about clinical studies
 Through survey outreach, patients also provide feedback and insights on their clinical trial experiences and the burden of disease, allowing for more optimal protocol design and patient-centric approaches to study recruitment and participation

 Outside of Better Together, LabCorp shares de-identified lab data with Covance, allowing for analysis of diseases/conditions of potential interest to study sponsors
 As a healthcare provider and HIPAA covered entity, LabCorp's use and disclosure of protected health information (PHI) is subject to HIPAA
 Any outreach by LabCorp to other healthcare providers/patients regarding clinical research that involves the use of PHI is done in accordance with the HIPAA Privacy Rule

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Frederick J. Derosier, D.O.
 D.O. from the New York College of Osteopathic Medicine; 10 years of private practice experience as an internist
 17 years of experience, primarily in neuroscience and rare diseases, in the pharmaceutical and biotechnology industry; joined Covance in 2017
 Co-chairs the Covance pan-enterprise Advanced Therapies, Drugs, and Devices Development group which supports the development advanced therapeutic technologies,
 Executive Director, Covance Rare Diseases and Pediatrics Team, focusing on strategic considerations for patient-centric drug development within rare diseases.
 Member of the American Academy of Neurology and has authored or co-authored numerous peer-reviewed journal articles, abstracts and presentations at industry conferences
 Email: frederick.derosier@covance.com
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