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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
4
Overview
Definitions
Goals and expectations
FDA experience with Real World Data (RWD)/Real World Evidence (RWE)
Foundational activities
Looking forward
5
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.
6
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
7
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
8
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
9
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
9
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
10
12
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
13
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
15
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
16
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
17
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
18
Demonstration Projects-Assessing Data Fitness
Oncology Center for Excellence : Information Exchange and Data Transformation (INFORMED)
Contact: Sean Khozin, MD
ASCO Annual Meeting
19
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
20
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
21
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
22
Spectrum of Reliance on RWD
23
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
24
Acknowledgments
Melissa Robb Dianne Paraoan Robert Ball Michael Blum Laura Esserman Leslie Curtis Sean Khozin Mitra Rocca Mary Ann Slack Vaishali Popot
25
Questions/ Comments
mailto:[email protected]
27
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-