Utilizing shared internal control arms and historical information in small-sized platform clinical trials

ABSTRACT

Recruitment of patients in concurrent control arms can be very challenging for clinical trials for pediatric and rare diseases. Innovative approaches, such as platform trial designs, including shared internal control arm(s), can potentially reduce the needed sample size, improving the efficiency and speed of the drug development program. Furthermore, historical borrowing, which involves leveraging information from control arms in previous relevant clinical trials, may further enhance a clinical trial’s efficiency. In this paper, we discuss platform trials highlighting their advantages and limitations. We then compare various strategies that borrow historical data or information, such as pooling data from different studies, analyzing data from studies separately, test-then-pool, dynamic pooling, and Bayesian hierarchical modeling, which focuses on the meta-analytic-predictive (MAP) prior. We further propose a procedure to illustrate the feasibility of utilizing historical controls under a platform setting and describe the statistical performance of our method via simulations.

KEYWORDS:

• Platform trials
• historical borrowing
• Bayesian
• rare disease

Acknowledgments

The authors express their gratitude to Dr. Kathleen Donohue for her valuable and constructive suggestions during the planning and development of this research work.

Disclosure statement

This article reflects the views of the authors and should not be construed to represent the FDA’s views or policies.

Additional information

Funding

This work was supported by the ORISE Research Program of the U.S. Food and Drug Administration.