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Proposal 1450

Title of the Proposed Research

Understanding effectiveness of new drugs in older adults shortly after market entry.

Lead Researcher

Shirley V Wang


Brigham and Women's Hospital and Harvard Medical School

Funding Source


Potential Conflicts of Interest

Consultant for Aetion, Inc. a software company. Principal Investigator on investigator initiated grant from Novartis.Consultant for Aetion, Inc. a software company. Principal Investigator on investigator initiated grant from Novartis.Principal Investigator of an investigator-initiated unrestricted grant from Baxalta and Novartis Corporation to Brigham and Women's Hospital, unrelated to the topic of this study.Consultant for Aetion, Inc. a software company. Principal investigator on investigator initiated grant from Merck.Served on numerous Data Monitoring Safety Boards, including the JUPITER trial. He has received research support from AstraZeneca and Novartis.

Data Sharing Agreement Date

30 March 2017

Lay Summary

When a new drug enters the market, comparative effectiveness evidence is often comprised solely of evidence from the randomized clinical trials (RCTs) which led to regulatory agency approval. Older adults are major consumers of drugs and other therapeutics and underrepresented in randomized clinical trials. During the critical early period after a new drug enters the market, evidence from RCTs may not reflect the average experience for the types of patients actually treated and there is insufficient accrual of experience in longitudinal healthcare databases for robust evidence generation.

At this critical juncture, combining evidence can enhance understanding of net benefit of new drugs in the older, sicker populations who are actually treated in practice. However, appropriate methods for integrating pre-market RCT and early post-market comparative effectiveness evidence to guide clinical practice have not yet been identified. We will explore these issues in two case studies. For each case study, we will obtain individual level data from pre-market RCTs and create observational cohorts comprised of initiators of the new drug and comparator using Medicare data. We will use complex weighting techniques to re-distribute baseline characteristics from RCT participants to match the distribution of characteristics observed in routine care of older adults in Medicare during early as well as later post-market experience with the new drugs.

Specifically we will research: (1) How can innovative application of methods to combine individual-level data from pre-market RCTs and early post-market observational data accelerate understanding of effectiveness and safety of new to market medications in older patients who are typically underrepresented in RCTs? (2) How can we evaluate and understand reasons for differences in treatment effect estimates from pre-market RCTs and observational data in the early post-marketing time period?

This project will produce a framework for combining pre-market RCT and early post-market evidence as a means to accelerate understanding of treatment effectiveness in older adults with multiple comorbidities. Use of this framework will provide early insights and clinical guidance to geriatricians on use of new drugs in their patients shortly after market entry. Because the methods used in this project are designed to provide early evidence that reflect average effectiveness in the types (and subtypes) of patients actually treated as part of routine care as opposed to average effectiveness in participants of a trial, the impact of this project will be particularly profound for new medications that target older, sicker patients typically underrepresented in trials. The output of this project will be made public as publications in peer-reviewed journals.

Study Data Provided

BI-1160.46: Phase III Study Testing Efficacy & Safety of Oral Dabigatran Etexilate vs Warfarin for 6 m Treatment for Acute Symp Venous Thromboembolism (VTE)
BI-1160.26: Randomized Evaluation of Long Term Anticoagulant Therapy (RE-LY) With Dabigatran Etexilate
NOVARTIS-CLCZ696B2314: A multicenter, randomized, double-blind, parallel group, active-controlled study to evaluate the efficacy and safety of LCZ696 compared to enalapril on morbidity and mortality in patients with chronic heart failure and reduced ejection fraction

Statistical Analysis Plan

Publication Citation

The publication citation will be added after the research is published.

Summary Results

Results summary or link will be posted when available.