An innovative approach to rare disease clinical development

Over the last ten years, the pharmaceutical industry has increasingly relied on innovative trial designs to expedite the development and approval of medical products, notably for rare diseases and for serious and life-threatening conditions. Indeed, developing and approving medical products swiftly is of paramount importance to all concerned: the public, sponsors, and the Food and Drug Administration (FDA). 

Given the many types of, and intended uses for drugs, the FDA has flexibility in how it applies regulatory standards. Of particular interest is how the FDA exercises its scientific judgment in regulating clinical trials for serious and life-threatening diseases.

While randomised clinical trials (RCTs) remain the most reliable trial design for characterising the safety and effectiveness of medical products, RCTs may be unfeasible or unethical in the study of treatments for rare diseases. To overcome issues relating to the assembly and retention of sufficiently large control arms, researchers may opt to conduct single-arm trials and supplement those findings with data from external control arms.

This briefing document describes external control arms and provides concise information on the FDA’s regulatory precedent regarding their acceptable use. It also summarises the most salient recommendations for sponsors from the FDA’s Draft Guidance for Industry on Considerations for the Design and Conduct of Externally Controlled Trials for Drug and Biological Products.