Real World EvidenceA Path Forward

Jacqueline Corrigan-CurayDirector

Office of Medical Policy Center for Drug Evaluation and Research

FDA September 13, 2017

Presenter Disclosure Information

Jacqueline Corrigan-Curay, JD MD

FINANCIAL DISCLOSURE:

No relevant financial relationship exists

The views expressed herein are those of the author and should not be

construed as FDAs views or policies

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Overview

Definitions

Goals and expectations

FDA experience with Real World Data (RWD)/Real World Evidence (RWE)

Foundational activities

Looking forward

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Definitions

Real-World Data (RWD) are data relating to patient health status and/or the delivery of health care routinely collected from a variety of sources.

Real-World Evidence (RWE) is the clinical evidence regarding the usage and potential benefits or risks of a medical product derived from analysis of RWD.

RWD include data derived from electronic health records (EHRs), claims and billing data, data from product and disease registries, patient-generated data including in home-use settings, and data gathered from other sources that can inform on health status, such as mobile devices.

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RWE: What are the Goals?

Maximize the opportunities to have regulatory decisions incorporate data/evidence from settings that more closely reflect clinical practice

Increase the diversity of populations

Improve efficiencies

o Population identification/selection

o Reduce duplicative capture of data

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RWE: What are the Expectations?

21St Century Cures

FDA shall establish a program

to evaluate the potential use of

real world evidence (RWE) to

support:

approval of new indication

for a drug approved under

section 505(c)

satisfy post-approval study

requirements

Real world evidence means data regarding the usage, or the potential benefitsor risks, of a drug derived from sources other than traditional clinical trials

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21st Century Cures

Program will be based on a framework that:

Categorizes sources of RWE and gaps in data collection activities

Identifies standards and methodologies for collection and analysis

Describes the priority areas, remaining challenges and potential pilot opportunities that the program will address

Framework will be developed in consultation

with stakeholders

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PDUFA VI Commitments

Enhance use of RWE in regulatory decision making

Conduct a public workshop to gather input into topics related to the use of RWE for regulatory decision-making

Initiate appropriate activities (e.g. pilot studies or methodology development projects) to address key issues in the use of RWE for regulatory decision making purposes

Publish draft guidance on how RWE can contribute to the assessment of safety and effectiveness in regulatory submissions (e.g. supplemental applications, post-marketing applications)

FDA Experience with RWD/RWE

https://www.sentinelinitiative.org/

425 million person years of observation

time

43 million people currently accruing new

data

5.9 billion pharmacy dispensings

7.2 billion unique medical encounters

42 million people with at least one

laboratory test result

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large numbers of reported cases of

bleeding with dabigatran is an example of

stimulated reporting. The Mini-Sentinel

assessment suggests that bleeding rates

with dabigatran are not higher than those

with warfarin, a finding that is consistent with

the results of RE-LY

-April 2013

Making Informed Decisions

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Signal Identification:Potential safety

concern identified

Signal Refinement:

Initial evaluation of safety concerns

Signal Evaluation:

Detailed assessment

Post-Market Safety Assessment

Modular Programs

>Level 2 Modular Programs/

Protocol-based Assessments

Data Mining

(e.g.

TreeScan)

Case Reports RegistriesObservational

StudiesClinical Trials

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Epidemiology Final Guidance

Pertains to pharmacoepidemiology

safety studies using electronic

healthcare data

Final guidance was issued May 14,

2013

Real-world evidence can inform therapeutic development,

outcomes research, patient care, research on health

systems, quality improvement, safety surveillance and

well-controlled effectiveness trials

As we adapt the tools and methods of traditional trials to

real-world data settings, we must consider the

components of such trials that are critical to obtaining

valid results and minimizing bias.

Discussions of real world evidence must be informed by a

clear understanding of the methods used, so that the best

methods that have been developed and validated can be

combined with the most appropriate research settings.N ENGL J MED 375;23 December 8, 2016

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Turning RWD into RWE

RWD Fitness for

useRWE Study Design

RWE Study Design

RWD Assessing Fitness for

Use

Regulatory Consider-

ations

Data Standards

and Implement-

ation

Engage with FDA early on this journey

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Laying the Foundation

Stakeholder Engagement

Demonstration Projects

Guidances

Data Standards

Use of Electronic

Informed Consent

FDAS THERAPEUTIC AREA

STANDARDS PROJECT

Of the 54 TAs prioritized, 44 have started with 21 of those completed as of Feb 2017

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Demonstration Projects-Assessing Data Fitness

Collaboration Duke Clinical Research Institute and GlaxoSmithKline

Supported by FDA

Assess EHR ability to: Facilitate recruitment

Populate baseline characteristics

Identify clinical endpoints

July 14, 2017: Leveraging Electronic Health Data in a Multinational Clinical Trial: Early Learnings from the HARMONY-Outcomes EHR Ancillary Study

http://www.rethinkingclinicaltrials.org/grand-rounds-7-14-17/

Effect of Albiglutide, When Added to Standard Blood Glucose Lowering Therapies,on Major Cardiovascular Events in Subjects With Type 2 Diabetes Mellitus NCT02465515

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Demonstration Projects-Assessing Data Fitness

Oncology Center for Excellence : Information Exchange and Data Transformation (INFORMED)

Contact: Sean Khozin, MD

ASCO Annual Meeting

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Demonstration Projects-Assessing Data Fitness /Standards

OneSource: enter the right clinical data once, use many times

FDA collaboration with Dr. Laura Esserman, UCSF

Integration of standards based tools into the EHR to bring together health care and research

Demonstration in breast cancer clinical trials

Courtesy of Dr. Laura Esserman and Susan Dubman

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Data Standards Demonstration

Networks of observational data use different Common data Models

Open, consensus-based standards might not be leveraged in these CDMs (ex: CDISC, HL7)

There is a need to facilitate interoperability among these collaborations

FUTURE State

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https://www.sentinelinitiative.org/sites/default/files/About/IMPACT-AFib_Protocol_Public_Comment_03012017.pdf

Demonstration Projects-Evidence Generation

IMPLEMENTATION OF A RANDOMIZED CONTROLLED TRIAL TO

IMPROVE TREATMENT WITH ORAL ANTICOAGULANTS IN PATIENTS

WITH ATRIAL FIBRILLATION (IMPACT-AFib)

An individually randomized trial of a practice and

patient level educational intervention to increase

anticoagulant use for individuals with atrial

fibrillation and increased risk of stroke (i.e.

CHA2DS2-VASc score 2). This project is a proof

of concept effort, the first trial conducted using

Sentinel Infrastructure, and will inform future

interventional studies that are designed to utilize

existing healthcare data as part of their design.

9% of people >65 years have Afib

AFib increases stroke risk by 4-5x

Oral anticoagulants significantly decrease risk of stroke

Source -- CDC Atrial Fibrillation Fact Sheet

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Spectrum of Reliance on RWD

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Looking Forward

Continued engagement with stakeholders to identify the key questions that FDA needs to answer to facilitate sponsor use of RWD and RWE for regulatory decisions

Provide appropriate guidance(s)

Identify knowledge gaps and support appropriate demonstration projects to facilitate development of RWE for regulatory decisions

Develop a framework and program

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Acknowledgments

Melissa Robb Dianne Paraoan Robert Ball Michael Blum Laura Esserman Leslie Curtis Sean Khozin Mitra Rocca Mary Ann Slack Vaishali Popot

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Questions/ Comments

CDERMedicalPolicy-RealWorldEvidence@fda.hhs.gov

mailto:CDERMedicalPolicy-RealWorldEvidence@fda.hhs.gov

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Turning RWD into RWE

Defining the

scientific question

Identify suitable trial

design

Selection of RWD Sources that are Fit for

Purpose

Data standards/ analytics

Ensure compliance

with FDA Regs

e.g. Part 11 and GCP

Submission of RWE for

regulatory action

Decision

Public Meeting: A Framework for Regulatory Use of Real-