Reflecting on EMA Reflections on Platform Trials

In this episode of "In the Interim…", Dr. Scott Berry and Dr. Kert Viele, Director of Research at Berry Consultants, review the European Medicines Agency's draft reflection paper on methodological aspects in confirmatory platform trials. They walk through the paper's definition of a platform trial and explain why the shared control arm is the source of both the efficiency and the complexity of these designs. Scott and Kert discuss the paper's preference for constant allocation ratios between each arm and control, its position that response adaptive randomization is not supported, two-stage randomization with multiple placebos, and the strong preference given to concurrent controls. They make the case that non-concurrent controls, adjusted for time, are high-quality controls, and welcome the paper's view that they are preferable to external controls. The episode closes with the risk of multiple false positive decisions from a common control, disjunctive and conjunctive power, and when multiplicity adjustment is warranted, with overall praise for a clear and well-constructed paper.Key HighlightsThe shared control arm as the source of both efficiency and complexity in platform trials.Constant allocation ratios, and the paper's hard no on response adaptive randomization.Two-stage randomization, multiple placebos, and testing whether placebo groups can be pooled.A strong preference for concurrent controls, and the case for time-adjusted non-concurrent controls.Internal non-concurrent controls preferred over external controls.Multiple false positive decisions, and marginal, disjunctive, and conjunctive power.When multiplicity adjustment applies across arms, doses, and related families of hypotheses.For more, visit us at https://www.berryconsultants.com/