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

Lead Investigator: Shirley Wang, Brigham and Women’s Hospital
Title of Proposal Research: Understanding effectiveness of new drugs in older adults shortly after market entry
Vivli Data Request: 5950
Funding Source: None
Potential Conflicts of Interest: In the last 3 years, Dr. Wang has received salary support from Boehringer Ingelheim, Novartis Pharmaceuticals, and Johnson & Johnson for unrelated work

Summary of the Proposed Research:

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 and discrete event simulation 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.

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.

Requested Studies:

Randomized Evaluation of Long Term Anticoagulant Therapy (RE-LY) Comparing the Efficacy and Safety of Two Blinded Doses of Dabigatran Etexilate With Open Label Warfarin for the Prevention of Stroke and Systemic Embolism in Patients With Non-valvular Atrial Fibrillation: Prospective, Multi-centre, Parallel-group, Non-inferiority Trial (RE-LY Study)
Sponsor: Boehringer-Ingelheim
Study ID: NCT00262600
Sponsor ID: 1160.26

A Phase III, Randomised, Double Blind, Parallel-group Study of the Efficacy and Safety of Oral Dabigatran Etexilate (150 mg Bid) Compared to Warfarin (INR 2.0-3.0) for 6 Month Treatment of Acute Symptomatic Venous Thromboembolism, Following Initial Treatment (5-10 Days) With a Parenteral Anticoagulant Approved for This Indication (RE-COVER II)
Sponsor: Boehringer-Ingelheim
Study ID: NCT00680186
Sponsor ID: 1160.46