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Abstract:
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Master protocols are used to investigate multiple therapies, multiple biomarker-defined patient subgroups, and/or multiple diseases or disease subtypes under a single overarching protocol. Their use grew out of the precision medicine environment to address questions about what treatment works best for what type of patient. Master protocols are attractive to patients and patient advocates because they provide multiple treatment options under one protocol, thereby avoiding the need for patients to be separately screened for each trial, especially when treatments are linked to biomarker profiles. The FDA often advocates for their use as a collaborative tool that can enhance efficient and timely drug development in a competitive commercial landscape. Master protocols capitalize on similarities among elements of trial design and conduct and use of a shared trial infrastructure, which can increase efficiency relative to conducting separate trials for each therapy. Hurdles include the need for considerable up-front investment, regulatory buy-in, and sponsors that are willing to test drugs in collaboration with others. The most common master protocol design is an adaptive platform design that allows promising agents to graduate for further study, agents with low probabilities of success to be terminated early, and new agents to enter the study in a perpetual manner. With the outbreak of Covid-19 in the US early in 2020, the NIH announced the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV), a public-private partnership coordinated by the Foundation for the NIH and consisting of representatives from the NIH, FDA, and other government agencies; the European Medicines Agency (EMA); academic and philanthropic organizations; and numerous pharmaceutical companies. The consortium selected master protocols as a key component of their coordinated research strategy to investigate Covid -19 treatments in both in- and out-patient populations. Three master protocols were launched within a matter of months, and as of this writing a 6th is in the final planning stage. In this presentation, I will provide an overview of master protocols and a brief history of their evolution, and then discuss design considerations for using master protocols in a pandemic and some lessons learned from the ACTIV experience.
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