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Statistical Communications in Infectious Diseases

Editor-in-Chief: Evans, Scott

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A Sequential Phase 2b Trial Design for Evaluating Vaccine Efficacy and Immune Correlates for Multiple HIV Vaccine Regimens

Peter B. Gilbert
  • Fred Hutchinson Cancer Research Center and University of Washington
/ Douglas Grove
  • Fred Hutchinson Cancer Research Center
/ Erin Gabriel
  • University of Washington
/ Ying Huang
  • Fred Hutchinson Cancer Research Center
/ Glenda Gray
  • University of the Witwatersrand
/ Scott M. Hammer
  • Columbia University Medical Center
/ Susan P. Buchbinder
  • San Francisco Department of Public Health and University of California, San Francisco
/ James Kublin
  • Fred Hutchinson Cancer Research Center
/ Lawrence Corey
  • Fred Hutchinson Cancer Research Center and University of Washington
/ Steven G. Self
  • Fred Hutchinson Cancer Research Center and University of Washington
Published Online: 2011-10-04 | DOI: https://doi.org/10.2202/1948-4690.1037

Five preventative HIV vaccine efficacy trials have been conducted over the last 12 years, all of which evaluated vaccine efficacy (VE) to prevent HIV infection for a single vaccine regimen versus placebo. Now that one of these trials has supported partial VE of a prime-boost vaccine regimen, there is interest in conducting efficacy trials that simultaneously evaluate multiple prime-boost vaccine regimens against a shared placebo group in the same geographic region, for accelerating the pace of vaccine development. This article proposes such a design, which has main objectives (1) to evaluate VE of each regimen versus placebo against HIV exposures occurring near the time of the immunizations; (2) to evaluate durability of VE for each vaccine regimen showing reliable evidence for positive VE; (3) to expeditiously evaluate the immune correlates of protection if any vaccine regimen shows reliable evidence for positive VE; and (4) to compare VE among the vaccine regimens. The design uses sequential monitoring for the events of vaccine harm, non-efficacy, and high efficacy, selected to weed out poor vaccines as rapidly as possible while guarding against prematurely weeding out a vaccine that does not confer efficacy until most of the immunizations are received. The evaluation of the design shows that testing multiple vaccine regimens is important for providing a well-powered assessment of the correlation of vaccine-induced immune responses with HIV infection, and is critically important for providing a reasonably powered assessment of the value of identified correlates as surrogate endpoints for HIV infection.

Keywords: HIV vaccine efficacy clinical trial; immune correlate of protection; one-way crossover design; surrogate endpoint for HIV infection; two-phase sampling

About the article

Published Online: 2011-10-04



Citation Information: Statistical Communications in Infectious Diseases, ISSN (Online) 1948-4690, DOI: https://doi.org/10.2202/1948-4690.1037. Export Citation

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[1]
Ying Huang, Peter B. Gilbert, and Julian Wolfson
Biometrics, 2013, Volume 69, Number 2, Page 301

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