Some statistical issues in HIV vaccine trials.
Efficacy trials of prophylactic HIV vaccines will be among the most difficult clinical trials ever attempted. Not only will there be challenges with the recruitment and retention of high-risk uninfected individuals, there will be many statistical challenges to the design, conduct, analysis, and interpretation of these trials. General features of an efficacy trial are described, including choice for the primary endpoint and testing for and estimating vaccine efficacy. Secondary objectives of trials are also discussed. These include determining the correlates of protective immunity, assessing the impact of HIV genetic variation on vaccine efficacy, and using biological markers such as viral load and CD4+ lymphocyte cell count to gain insight on a vaccine's ability to prevent or delay disease. The use of biological markers as surrogates for disease outcome is discussed. Last, trial designs for studying several candidate vaccines or other HIV prevention strategies in a single trial are examined.
Rida
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Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
Lawrence
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D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000145:classification / Q000235:genetics / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D000163:Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D000328:Adult; D000818:Animals; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002986:Clinical Trials as Topic; D017321:Clinical Trials, Phase I as Topic; D015331:Cohort Studies; D004195:Disease Models, Animal; D004989:Ethics; D005260:Female; D015658:HIV Infections / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control* / Q000635:transmission; D006679:HIV Seropositivity / Q000175:diagnosis; D015497:HIV-1 / Q000235:genetics; D018451:Homosexuality, Male; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D008253:Macaca mulatta; D008297:Male; D002679:Pan troglodytes; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D012107:Research Design; D018401:Sample Size; D011477:Sex Work; D013997:Time Factors; D016896:Treatment Outcome
D016915:AIDS Vaccines; D015415:Biomarkers