Minimizing Patient Burden Through the Use of Historical Subject-Level Data in Innovative Confirmatory Clinical Trials: Review of Methods and Opportunities

• Published in: Therapeutic innovation & regulatory science Vol. 52; no. 5; p. 546
• Main Authors: Lim, Jessica, Walley, Rosalind, Yuan, Jiacheng, Liu, Jeen, Dabral, Abhishek, Best, Nicky, Grieve, Andrew, Hampson, Lisa, Wolfram, Josephine, Woodward, Phil, Yong, Florence, Zhang, Xiang, Bowen, Ed
• Format: Journal Article
• Language: English
• Published: Switzerland 01-09-2018
• Subjects: Bayes Theorem; Clinical Trials as Topic; Control Groups; Drug Approval; Historically Controlled Study; Humans; Propensity Score; Rare Diseases; Sample Size; TransCelerate; informative prior; historical controls; Bayesian; propensity score
• ISSN: 2168-4804
• DOI: 10.1177/2168479018778282

The goal of clinical trial research is to deliver safe and efficacious new treatments to patients in need in a timely and cost-effective manner. There is precedent in using historical control data to reduce the number of concurrent control subjects required in developing medicines for rare diseases and other areas of unmet need. The purpose of this paper is to provide a review for a regulatory and industry audience of the current state of relevant statistical methods, and of the uptake of these approaches and the opportunities for broader use of historical data in confirmatory clinical trials. General principles to consider when incorporating historical control data in a new trial are presented. Bayesian and frequentist approaches are outlined including how the operating characteristics for such a trial can be obtained. Finally, examples of approved new treatments that incorporated historical controls in their confirmatory trials are presented.