Aiding the Adoption of Master Protocols by Optimizing Patient Engagement.

Master protocols (MPs) are an important addition to the clinical trial repertoire. As defined by the U.S. Food and Drug Administration (FDA), this term means "a protocol designed with multiple sub-studies, which may have different objectives (goals) and involve coordinated efforts to evaluate one or more investigational drugs in one or more disease subtypes within the overall trial structure." This means we now have a unique, scientifically based MP that describes how a clinical trial will be conducted using one or more potential candidate therapies to treat patients in one or more diseases. Patient engagement (PE) is also a critical factor that has been recognized by FDA through its Patient-Focused Drug Development (PFDD) initiative, and by the European Medicines Agency (EMA), which states on its website that it has been actively interacting with patients since the creation of the Agency in 1995. We propose that utilizing these PE principles in MPs can make them more successful for sponsors, providers, and patients. Potential benefits of MPs for patients awaiting treatment can include treatments that better fit a patient's needs; availability of more treatments; and faster access to treatments. These make it possible to develop innovative therapies (especially for rare diseases and/or unique subpopulations, e.g., pediatrics), to minimize untoward side effects through careful dose escalation practices and, by sharing a control arm, to lower the probability of being assigned to a placebo arm for clinical trial participants. This paper is authored by select members of the American Statistical Association (ASA)/DahShu Master Protocol Working Group (MPWG) People and Patient Engagement (PE) Subteam. DahShu is a 501(c)(3) non-profit organization, founded to promote research and education in data science. This manuscript does not include direct feedback from US or non-US regulators, though multiple regulatory-related references are cited to confirm our observation that improving patient engagement is supported by regulators. This manuscript represents the authors' independent perspective on the Master Protocol; it does not represent the official policy or viewpoint of FDA or any other regulatory organization or the views of the authors' employers. The objective of this manuscript is to provide drug developers, contract research organizations (CROs), third party capital investors, patient advocacy groups (PAGs), and biopharmaceutical executives with a better understanding of how including the patient voice throughout MP development and conduct creates more efficient clinical trials. The PE Subteam also plans to publish a Plain Language Summary (PLS) of this publication for clinical trial participants, patients, caregivers, and the public as they seek to understand the risks and benefits of MP clinical trial participation.