The Use of Non-Concurrent Randomized Controls in Multi-Arm Adaptive Platforms Trials

• Activity Number: 296 - Biopharmaceutical Section P.M. Roundtable Discussion (Added Fee)
• Type: Roundtables
• Date/Time: Tuesday, August 9, 2022 : 12:30 PM to 1:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Ben Saville*
• Companies: Berry Consultants
• Keywords: temporal drift; non-concurrent controls; multi-arm clinical trials; staggered entry; adaptive platform trial; Bayesian

Abstract

Multi-arm platform trials investigate multiple agents simultaneously, typically with staggered entry and exit of experimental treatment arms versus a shared control arm. Recent applications in the COVID-19 pandemic highlight the benefits of platform trials in evaluating treatments with operational speed and statistical efficiency. In such settings, there is considerable debate whether to limit analyses for a treatment arm to concurrently randomized control subjects, or to allow comparisons to both concurrent and non-concurrent (pooled) control subjects. The potential bias from temporal drift over time is at the core of this debate. We discuss the use of time-adjusted analyses (both Bayesian and frequentist) to model potential temporal drift, and the tradeoffs between bias and precision that should be considered in the evaluation of treatments with staggered entry.