Rare diseases, which affect >30 million individuals in the United States (US), have historically taken a back seat to more common diseases such as cancer, diabetes, and heart disease in the clinical trials landscape, primarily due to trial design challenges in limited patient populations. Through public meetings and behind-the-scenes engagement with patients, the US Food and Drug Administration (FDA) has heard that regulatory flexibility is paramount to advancing drug development for rare diseases. Many of these diseases share molecular etiologies, and patients with those diseases could equally benefit from treatment with a single agent. Some of the most debilitating rare diseases affect the most vulnerable and cherished population – children. However, clinical trial design regulations and very small patient populations complicate the initiation of studies for these rare diseases. The use of basket trials – an approach that has led to the approval of groundbreaking oncology products – could be one solution to faster, more successful development of products for the rarest of rare diseases by targeting shared molecular etiologies instead of specific diseases.
Innovative Clinical Trial Designs for Rare Diseases
After the passage of the 21st Century Cures Act in 2016, innovative regulatory approaches paved the way for master protocol designs for oncology clinical trials. In the FDA’s 2022 Master Protocols: Efficient Clinical Trial Design Strategies to Expedite Development of Oncology Drugs and Biologics: Guidance for Industry, a basket trial is defined as “a master protocol designed to test a single investigational drug or drug combination in different populations defined by different cancers, disease stages for a specific cancer, histologies, number of prior therapies, genetic or other biomarkers, or demographic characteristics.” The agency emphasises that because master protocols are so complex, it is important that they are “well designed and well conducted” to ensure patient safety and to collect quality data that could support product approval.
