Predicting Treatment Effects of a New‐to‐Market Drug in Clinical Practice Based on Phase III Randomized Trial Results
Year: 2023
Type: article
Abstract: Trial results may not be generalizable to target populations treated in clinical practice with different distributions of baseline characteristics that modify the treatment effect. We used outcome models developed with trial data to predict treatment effects in Medicare populations. We used data from the Randomized Evaluation of Long‐Term Anticoagulation Therapy trial (RE‐LY), which investigated the effect of dabigatran vs. warfarin on stroke or systemic embolism (stroke/SE) among patients with atrial fibrillation. We developed outcome models by fitting proportional hazards models in trial data. Target populations were trial‐eligible Medicare beneficiaries who initiated dabigatran or warfarin in 2010–2011 (“early”) and 2010–2017 (“extended”). We predicted 2‐year risk ratios (RRs) and risk differences (RDs) for stroke/SE, major bleeding, and all‐cause death in the Medicare populations using the observed baseline characteristics. The trial and early target populations had similar mean (SD) CHADS2scores (2.15 (SD 1.13) vs. 2.15 (SD 0.91)) but different mean ages (71 vs. 79 years). Compared with RE‐LY, the early Medicare population had similar predicted benefit of dabigatran vs. warfarin for stroke/SE (trial RR = 0.63, 95% confidence interval (CI) = 0.50 to 0.76 and RD = −1.37%, −1.96% to −0.77%, Medicare RR = 0.73, 0.65 to 0.82 and RD = −0.92%, −1.26% to −0.59%) and risks for major bleeding and all‐cause death. The time‐extended target population showed similar results. Outcome model‐based prediction facilitates estimating the average treatment effects of a drug in different target populations when treatment and outcome data are unreliable or unavailable. The predicted effects may inform payers' coverage decisions for patients, especially shortly after a drug's launch when observational data are scarce.
DOI: 10.1002/cpt.2983
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: Understanding effectiveness of new drugs in older adults shortly after market entry, Generalizing data from randomized trials to predict long-term treatment outcomes in older populations, G4184428524, Randomized Cardiovascular Trials Duplicated Using Prospective Longitudinal Insurance Claims: Applying Techniques of Epidemiology (RCT DUPLICATE), Mid-Career Mentoring Award For Patient-Oriented Research in Frailty and Health Outcomes, New approaches to safety monitoring of novel systemic treatments for atopic dermatitis in clinical practice and underrepresented populations
OpenAlex ID: W4382181202