FDA Advances Innovative Clinical Trial Designs


Applied Clinical Trials

To encourage experimentation with more complex clinical trial strategies, FDA plans to launch a pilot program to assess complex studies proposed by sponsors.

To encourage experimentation with more complex clinical trial strategies, FDA plans to launch a pilot program to assess complex studies proposed by sponsors. At the same time, the agency is examining how innovative statistical approaches may support clinical trials for rare conditions that involve small patient populations.

Issues involved in using complex innovative designs (CID) in drug development and testing was the topic of a March 20 workshop organized by the Office of Biostatistics in the Center of Drug Evaluation and Research (CDER) [meeting agenda at https://www.fda.gov/downloads/Drugs/NewsEvents/UCM599228.pdf ]. The conference fulfills a provision of the 21st Century Cures legislation as well as the agreement for implementing the latest version of the Prescription Drug User Fee Act (PDUFA VI).

FDA reviewers and research experts from industry and academia examined a range of adaptive clinical trial studies and their advantages in enabling smaller, more efficient research programs [presentation details at https://www.fda.gov/downloads/Drugs/NewsEvents/UCM601630.pdf ]. A main concern is that trials should avoid erroneous conclusions and uncertain estimations. The group also examined the pros and cons of Bayesian applications and broader use of master protocols and platform trials to advance drug development, particularly for treating rare diseases and microbial infections.

The workshop concluded with a discussion on how best to design a CID pilot program to further advance the use of novel clinical trial methods. FDA will formally announce the pilot in the Federal Register and describe how the agency will select quarterly up to two highly innovative trial designs from sponsors to use as case studies for further discussion with agency reviewers. Sponsors have some concerns about disclosing confidential information through this process and are looking for flexibility and creativity from FDA.

Streamlining rare disease research

Another public workshop on utilizing innovative statistical methods and trial designs in rare disease drug development took place March 19, with an eye to issuing further guidance documents on the topic. Convened by the Duke-Robert J. Margolis Center for Health Policy at Duke University with support from FDA, the session brought together rare disease advocates with regulators and research experts to discuss the statistical challenges in conducting studies involving small populations that may be geographically dispersed. Trials for rare conditions are challenging often due to a lack of reliable study endpoints, outcome measures and biomarkers, as well as few natural history studies that often can inform clinical studies.

One proposal on the agenda [see


] addressed the use of prior data from early trials to inform phase 3 designs. Panels also discussed strategies for utilizing patient registries and natural history study data and for leveraging master protocols [see


]. FDA issued draft guidance in December 2017 on using platform trials to facilitate drug development in Gaucher’s disease, and these discussions may support extending this approach to other rare disease areas. 

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