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Not only will there be challenges with the recruitment and retention of high\u2010risk 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<jats:sup>+<\/jats:sup> 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.<\/jats:p>","DOI":"10.1002\/sim.4780131922","type":"journal-article","created":{"date-parts":[[2007,4,28]],"date-time":"2007-04-28T14:18:15Z","timestamp":1177769895000},"page":"2155-2177","source":"Crossref","is-referenced-by-count":19,"title":["Some statistical issues in HIV vaccine trials"],"prefix":"10.1002","volume":"13","author":[{"given":"Wasima N.","family":"Rida","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dale N.","family":"Lawrence","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,10,15]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001432-199304000-00014"},{"key":"e_1_2_1_3_2","first-page":"7","article-title":"HIV prevalence estimates and AIDS case projections for the United States: report based on a workshop","volume":"39","author":"Centers for Disease Control","year":"1990","journal-title":"HIV prevalence estimates and AIDS case projections for the United States: report based on a workshop"},{"key":"e_1_2_1_4_2","first-page":"124","volume-title":"The Invisible Invaders: The Story of the Emerging Age of Viruses","author":"Radetsky P.","year":"1991"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1925584"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.24.11478"},{"issue":"1","key":"e_1_2_1_7_2","first-page":"5195","article-title":"Use of novel DNA vectors and immunologic adjuvants in HIV vaccine development","volume":"8","author":"Liu M.","year":"1994","journal-title":"AIDS"},{"key":"e_1_2_1_8_2","first-page":"73","article-title":"Advances in AIDS vaccine development","volume":"57","author":"Koff W. 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