Designing an adaptive phase II/III trial to evaluate efficacy, safety and immune correlates of new TB vaccines in young adults and adolescents

Journal article

This article summarises the consensus arrived at a meeting of South African and international stakeholders on specific late phase clinical trial design issues integrating the investigation of immune correlates as an integral part of a phase III protocol for a preventative TB vaccine in an adolescent/adult population. The challenge ahead is to optimize the planning for phase 3 TB vaccine preventative trials, under resource constraints, given that there are no known correlates of protection to shorten and increase the efficiencies of efficacy trials. An adaptive, multi-arm, group sequentially designed trial protocol is proposed incorporating design features that address uncertainties arising from both advances in the field and dynamic study populations and disease states. Such a design allows modifications that protect research subjects, save time, and maximize the impact of scarce financial resources. Further, the protocol underwent joint review by regulators from several African nations at a meeting of the African Vaccine Regulatory Forum (AVAREF), a regional regulatory harmonization initiative, and recommendations are included. © 2012 Elsevier Ltd. All rights reserved.

Authors: Rustomjee, R; McClain, B; Brennan, M; McLeod, R; Chetty-Makkan, C

• Journal: Tuberculosis
• Volume: 93
• Issue: 2
• Pages: 136-142
• Publication date: 2013-03-01
• DOI: 10.1016/j.tube.2012.11.005
• EISSN: 1873-281X
• ISSN: 1472-9792
• Language: English
• Keywords: Adaptive design; Vaccine; Efficacy; Phase III clinical trial; Tuberculosis