Vaccine clinical trials with dynamic borrowing of historical controls: Two retrospective studies

• Published in: Pharmaceutical statistics : the journal of the pharmaceutical industry Vol. 22; no. 3; pp. 475 - 491
• Main Authors: Callegaro, Andrea, Karkada, Naveen, Aris, Emmanuel, Zahaf, Toufik
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Inc 01.05.2023; Wiley Subscription Services, Inc
• Subjects: adaptive design; Bayes Theorem; Bayesian inference; Clinical trials; Disease prevention; dynamic borrowing; historical controls; Human papillomavirus; Humans; Research Design; Retrospective Studies; Sample Size; vaccine efficacy; vaccine trials; Vaccines; dynamic borrowing; clinical trials; vaccine trials; Bayesian inference; vaccine efficacy; historical controls; adaptive design
• ISSN: 1539-1604; 1539-1612; 1539-1612
• DOI: 10.1002/pst.2283

Traditional vaccine efficacy trials usually use fixed designs with fairly large sample sizes. Recruiting a large number of subjects requires longer time and higher costs. Furthermore, vaccine developers are more than ever facing the need to accelerate vaccine development to fulfill the public's medical needs. A possible approach to accelerate development is to use the method of dynamic borrowing of historical controls in clinical trials. In this paper, we evaluate the feasibility and the performance of this approach in vaccine development by retrospectively analyzing two real vaccine studies: a relatively small immunological trial (typical early phase study) and a large vaccine efficacy trial (typical Phase 3 study) assessing prophylactic human papillomavirus vaccine. Results are promising, particularly for early development immunological studies, where the adaptive design is feasible, and control of type I error is less relevant.