The platform trial: an efficient strategy for evaluating multiple treatments.

The drug development enterprise is struggling. The development of new therapies is limited by high costs, slow progress, and a high failure rate, even in the late stages of development. Clinical trials are most commonly based on a “one population, one drug, one disease” strategy, in which the clinical trial infrastructure is created to test a single treatment in a homogeneous population. This approach has been largely unsuccessful for multiple diseases, including sepsis, dementia, and stroke. Despite promising preclinical and early human trials, there have been numerous negative phase 3 trials of treatments for Alzheimer disease1 and more than 40 negative phase 3 trials of neuroprotectants for stroke.2 Effective treatments for such diseases will likely require combining treatments to affect multiple targets in complex cellular pathways and, perhaps, tailoring treatments to subgroups defined by genetic, proteomic, metabolomic, or other markers.3 There has been increasing interest in efficient trial strategies designed to evaluate multiple treatments and combinations of treatments, in heterogeneous patient populations, with the capability to add new treatments in the future and eliminate investigational treatments lacking efficacy. The term “platform trial” is sometimes used to describe trials designed with these goals in mind, signifying the intent to build an experimental platform that will exist after the evaluation of any particular treatment.4 Currently, platform trials are enrolling patients or are under development in oncology, infectious diseases, neurology, and intensive care. Platform trials are an extension of adaptive trial design. An adaptive trial allows prespecified changes in key trial characteristics during the conduct of the trial in response to information accumulating during the trial; however, most adaptive trials focus on evaluating a single treatment in a single population. Examples of adaptive trials include traditional group-sequential trials, as well as trials incorporating reestimation of sample size or using variable randomization proportions (responseadaptive randomization).5 A platform trial is a type of adaptive trial designed to evaluate multiple treatments efficiently.