Journal Article

Characteristics, design, and statistical methods in platform trials: a systematic review

Laouénan, Cédric, Schönenberger, Christof Manuel, Massonnaud, Clément R., Briel, Matthias, Chiaborelli, Malena, Ehrenzeller, Selina, Griessbach, Alexandra, Gillibert, André

2025

Overview

Platform trials (PTs) are gaining popularity in clinical research due to their innovative and flexible methodologies. The objective was to determine the characteristics, methodological, and statistical practices in PTs. We identified PTs from trial registries and bibliographic databases up to August 2024. Eligible PTs were randomized controlled trials studying multiple interventions within a single population, with flexibility to add or drop arms. Data were extracted on trial status, design, statistical methods, and reporting practices. We identified 189 PTs. Most focused on infectious diseases (77, including 57 for COVID-19) and oncology (68). PT initiation peaked during the COVID-19 pandemic but has since stabilized at 84 active PTs, with 25 in planning. A complete master protocol was available for 47% (89/189) of PTs. Bayesian designs featured in 58/189 PTs vs. 56/189 frequentist trials, 20/189 trials utilizing both (unclear in 55/189 PTs). Overall, 25/111 trials (23%) were designed without a predetermined target sample size, all of which were Bayesian. Among these, 16 were explicitly reported as “perpetual” trials. The number of interim analyses was predetermined in 18% (10/57) of Bayesian trials vs. 58% (28/48) of frequentist trials. Simulations to evaluate operating characteristics were used in 93% (39/42) of Bayesian trials. Simulation reports were available in 67% (26/39) of cases, and the procedures were detailed for 62% (24/39) of trials. Only two trials shared the simulation code. PTs remain popular and increasingly diverse. Efforts to enhance transparency and reporting, especially in complex Bayesian PTs, are essential to ensure reliability and broader acceptance. •Bayesian designs were as common as frequentist designs.•Simulations to evaluate operating characteristics were used in 93% of Bayesian trials.•Simulation reports were available in only 67% of cases in Bayesian trials.•Simulation procedures were detailed in only 62% of cases in Bayesian trials.•Efforts are needed to enhance transparency and reporting of platform trial features.

• Publisher: Elsevier Inc,Elsevier Limited
• Subject: Adaptive clinical trials / Adaptive platform trials / Bayes Theorem / Bayesian analysis / Bayesian designs / Bayesian trials / Bibliographic data bases / Clinical trials / COVID-19 / COVID-19 - epidemiology / Design / Humans / Infectious diseases / Internal Medicine / Oncology / Pandemics / Platform trials / Randomized Controlled Trials as Topic - methods / Randomized Controlled Trials as Topic - statistics & numerical data / Reproducibility / Research Design / SARS-CoV-2 / Simulation / Statistical analysis / Statistical methods / Statistics / Systematic review