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

BACKGROUND AND

OBJECTIVE

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.