Researchers propose master protocols for rare neurological disease trials

A collaborative group of researchers has published a case for using master protocol trials to improve the efficiency of rare neurological disease research, with potential benefits including lower costs, greater testing capacity and faster delivery of treatments. The paper, “The Case for Master Protocols for Rare Neurological Diseases,” was published online in Annals of Neurology on July 21, 2026. Researchers from Kennedy Krieger Institute and University of Rochester Medicine led the publication with participation from other academic institutions, clinical-trial experts, patient organizations and consultants. The article presents master protocols as a proposed research strategy rather than reporting results from a completed clinical trial.

Master protocol trials allow multiple drugs, diseases or both to be investigated at the same time within a shared clinical framework. Possible formats include basket trials, umbrella trials, platform trials or a combination of these designs. By comparison, a traditional clinical trial generally requires a new framework for each drug or condition tested. Researchers argue that this approach could make rare-disease studies more efficient by allowing several investigations to proceed under one framework. However, the publication and its accompanying news release do not quantify the expected savings, increase in testing capacity or reduction in trial time, and they do not establish that master protocols have improved treatment delivery or patient outcomes.

The proposal addresses a substantial gap between the number of diagnosed neurological disorders and the number for which drug therapies have been approved. According to the Kennedy Krieger Institute’s news release, the US Food and Drug Administration approved 45 drug therapy options for neurological conditions during the past decade. Those options treated 26 different conditions, equivalent to about 4% of all diagnosed neurological disorders. Many people facing rare diseases still have no treatment options. These figures describe regulatory approvals and the wider treatment landscape; they do not show that master protocols have already produced effective treatments. Likewise, the anticipated acceleration of treatment delivery is a projection based on the proposed efficiency of the approach, not an observed clinical effect.

In the United States, a rare disease is defined as a condition affecting fewer than 200,000 people, although approximately one in ten people has received a rare-disease diagnosis. More than 10,000 rare diseases are known, and most display neurological symptoms ranging from impaired body control to developmental disabilities. Recent research has identified similar genetic markers in multiple disease conditions. The authors propose that these shared biological features, combined with the development of targeted gene therapies, could allow diseases with related genetic mutations to be evaluated within a master protocol. The release does not report patient testing of this strategy or results demonstrating the safety or efficacy of any treatment studied through it.

Lead author Jennifer Vermilion, director of the University of Rochester Batten Center of Excellence, said the collaboration behind the paper reflects the cooperative model that master protocols are intended to advance. “Working together, rather than in isolation, can help us answer important questions more efficiently and accelerate progress for patients and families,” she said. Erika Augustine, associate chief science officer and director of the Clinical Trials Unit at Kennedy Krieger Institute and senior author, said, “Families living with rare neurological diseases cannot afford to wait for scientific progress to move at a traditional pace.” She described master protocols as a more collaborative way to evaluate potential therapies and bring effective treatments to patients more efficiently. The publication resulted from work involving University of Rochester Medicine; Mass General Brigham, Spaulding Rehabilitation and Harvard Medical School; Berry Consultants; the Clinical Trials Transformation Initiative at Duke University; the Batten Disease Support, Research and Advocacy Foundation; Rady Children’s Health and UC Irvine; and Kennedy Krieger Institute. The news release identifies the research method as data and statistical analysis, while the publication is a strategic case for master protocols rather than an efficacy study.

Subject of Research: Use of master protocol trials in rare neurological disease research

Article Title: Master protocol trials could reimagine the future of rare disease research

Article References: Master protocol trials could reimagine the future of rare disease research. Original publication (Bibliographic details unavailable.)

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Keywords: rare neurological diseases, master protocols, clinical trials, basket trials, umbrella trials, platform trials, gene therapy, rare diseases, treatment development, research efficiency, Master, protocol