title: Lessons learnt from the first efficacy trial of a new infant tuberculosis vaccine since BCG.
abstract: BACKGROUND
  New tuberculosis (TB) vaccines are being developed to combat the global epidemic. A phase IIb trial of a candidate vaccine, MVA85A, was conducted in a high burden setting in South Africa to evaluate proof-of-concept efficacy for prevention of TB in infants.
  
  
  OBJECTIVE
  To describe the study design and implementation lessons from an infant TB vaccine efficacy trial.
  
  
  METHODS
  This was a randomised, controlled, double-blind clinical trial comparing the safety and efficacy of MVA85A to Candin control administered to 4-6-month-old, BCG-vaccinated, HIV-negative infants at a rural site in South Africa. Infants were followed up for 15-39 months for incident TB disease based on pre-specified endpoints.
  
  
  RESULTS
  2797 infants were enrolled over 22 months. Factors adversely affecting recruitment and the solutions that were implemented are discussed. Slow case accrual led to six months extension of trial follow up.
  
  
  CONCLUSIONS
  The clinical, regulatory and research environment for modern efficacy trials of new TB vaccines are substantially different to that when BCG vaccine was first evaluated in infants. Future infant TB vaccine trials will need to allocate sufficient resources and optimise operational efficiency. A stringent TB case definition is necessary to maximize specificity, and TB case accrual must be monitored closely.
authors: South African TB Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine (IIDMM) and School of Child and Adolescent Health, University of Cape Town, Brewelskloof Hospital, Haarlem Street, Worcester, Western Cape 6850, South Africa. michele.tameris@uct.ac.za
authors: Michele
authors: M
authors: Tameris
authors: Helen
authors: H
authors: McShane
authors: J Bruce
authors: JB
authors: McClain
authors: Bernard
authors: B
authors: Landry
authors: Stephen
authors: S
authors: Lockhart
authors: Angelique K K
authors: AK
authors: Luabeya
authors: Hennie
authors: H
authors: Geldenhuys
authors: Jacqui
authors: J
authors: Shea
authors: Gregory
authors: G
authors: Hussey
authors: Linda
authors: L
authors: van der Merwe
authors: Marwou
authors: M
authors: de Kock
authors: Thomas
authors: T
authors: Scriba
authors: Robert
authors: R
authors: Walker
authors: Willem
authors: W
authors: Hanekom
authors: Mark
authors: M
authors: Hatherill
authors: Hassan
authors: H
authors: Mahomed
mesh_terms: D001500:BCG Vaccine; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D018579:Patient Selection; D012107:Research Design; D013019:South Africa / Q000453:epidemiology; D016896:Treatment Outcome; D014376:Tuberculosis / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines; D014613:Vaccines, Attenuated; D019444:Vaccines, DNA; D014765:Viral Vaccines
chemical_list: D001500:BCG Vaccine; C549320:MVA 85A; D032581:Tuberculosis Vaccines; D014613:Vaccines, Attenuated; D019444:Vaccines, DNA; D014765:Viral Vaccines