Platform trials

Abstract

For the past few years, platform trials have experienced a significant increase, recently amplified by the COVID-19 pandemic. The implementation of a platform trial is particularly useful in certain pathologies, particularly when there is a significant number of drug candidates to be assessed, a rapid evolution of the standard of care or in situations of urgent need for evaluation, during which the pooling of protocols and infrastructure optimizes the number of patients to be enrolled, the costs, and the deadlines for carrying out the investigation. However, the specificity of platform trials raises methodological, ethical, and regulatory issues, which have been the subject of the round table and which are presented in this article. The round table was also an opportunity to discuss the complexity of sponsorship and data management related to the multiplicity of partners, funding, and governance of these trials, and the level of acceptability of their findings by the competent authorities.

Keywords: Adaptive trial; Platform trial; Randomized controlled trial.

Figure 1

Schematic representation of the design of a platform trial comparing three new treatments to the standard care (SOC). The rectangles represent the enrollment periods, the fine lines the follow-up periods. The end of follow-up for one arm is reached either at the time of its final analysis or after one of its interim analyses showing efficacy or futility. When the necessary number of subjects is included in an arm, enrollment in the arm is suspended. The new patients are then randomized between the arms that did not reach their headcount and the control arm. When all active arms have reached their expected numbers, enrollment in the study is suspended. SOC* is the new SOC based on treatment B after demonstrating its clinical interest. There is a time limit between the availability of the findings concerning treatment B and its adoption as a new SOC. In the case of treatment C, only patients enrolled during the period corresponding to the new SOC may be used (contemporaneous principle). The first patients enrolled in arm C are not usable, as their contemporaneous control group is no longer loyal at the time of switching to the new SOC.