title: Designing an adaptive phase II/III trial to evaluate efficacy, safety and immune correlates of new TB vaccines in young adults and adolescents.
abstract: 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.
authors.affiliation: Vaccine Development, Emergent BioSolutions, South Africa. rustomjeer@ebsi.com
authors.forename: R
authors.initials: R
authors.lastname: Rustomjee
authors.forename: B
authors.initials: B
authors.lastname: McClain
authors.forename: M J
authors.initials: MJ
authors.lastname: Brennan
authors.forename: R
authors.initials: R
authors.lastname: McLeod
authors.forename: C M
authors.initials: CM
authors.lastname: Chetty-Makkan
authors.forename: H
authors.initials: H
authors.lastname: McShane
authors.forename: W
authors.initials: W
authors.lastname: Hanekom
authors.forename: G
authors.initials: G
authors.lastname: Steel
authors.forename: H
authors.initials: H
authors.lastname: Mahomed
authors.forename: A M
authors.initials: AM
authors.lastname: Ginsberg
authors.forename: J
authors.initials: J
authors.lastname: Shea
authors.forename: S
authors.initials: S
authors.lastname: Lockhart
authors.forename: S
authors.initials: S
authors.lastname: Self
authors.forename: G J
authors.initials: GJ
authors.lastname: Churchyard
mesh_terms: D000293:Adolescent; D000328:Adult; D017322:Clinical Trials, Phase II as Topic / Q000379:methods* / Q000592:standards; D017326:Clinical Trials, Phase III as Topic / Q000379:methods* / Q000592:standards; D004311:Double-Blind Method; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design; D018401:Sample Size; D016896:Treatment Outcome; D014376:Tuberculosis / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
chemical_list: D032581:Tuberculosis Vaccines