{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T10:18:31Z","timestamp":1777544311581,"version":"3.51.4"},"reference-count":47,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2018,10,17]],"date-time":"2018-10-17T00:00:00Z","timestamp":1539734400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI100654, DP2HD084070, and P30 AI50410"],"award-info":[{"award-number":["R01AI100654, DP2HD084070, and P30 AI50410"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Clinical Trials"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Intention-to-treat comparisons of randomized trials provide asymptotically consistent estimators of the effect of treatment assignment, without regard to compliance. However, decision makers often wish to know the effect of a per-protocol comparison. Moreover, decision makers may also wish to know the effect of treatment assignment or treatment protocol in a user-specified target population other than the sample in which the trial was fielded. Here, we aimed to generalize results from the ACTG A5095 trial to the US recently HIV-diagnosed target population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We first replicated the published conventional intention-to-treat estimate (2-year risk difference and hazard ratio) comparing a four-drug antiretroviral regimen to a three-drug regimen in the A5095 trial. We then estimated the intention-to-treat effect that accounted for informative dropout and the per-protocol effect that additionally accounted for protocol deviations by constructing inverse probability weights. Furthermore, we employed inverse odds of sampling weights to generalize both intention-to-treat and per-protocol effects to a target population comprising US individuals with HIV diagnosed during 2008\u20132014.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 761 subjects in the analysis, 82 dropouts (36 in the three-drug arm and 46 in the four-drug arm) and 59 protocol deviations (25 in the three-drug arm and 34 in the four-drug arm) occurred during the first 2\u2009years of follow-up. A total of 169 subjects incurred virologic failure or death. The 2-year risks were similar both in the trial and in the US HIV-diagnosed target population for estimates from the conventional intention-to-treat, dropout-weighted intention-to-treat, and per-protocol analyses. In the US target population, the 2-year conventional intention-to-treat risk difference (unit: %) for virologic failure or death comparing the four-drug arm to the three-drug arm was \u22120.4 (95% confidence interval: \u22126.2, 5.1), while the hazard ratio was 0.97 (95% confidence interval: 0.70, 1.34); the 2-year risk difference was \u22120.9 (95% confidence interval: \u22126.9, 5.3) for the dropout-weighted intention-to-treat comparison (hazard ratio\u2009=\u20090.95, 95% confidence interval: 0.68, 1.32) and \u22120.7 (95% confidence interval: \u22126.7, 5.5) for the per-protocol comparison (hazard ratio\u2009=\u20090.96, 95% confidence interval: 0.69, 1.34).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>No benefit of four-drug antiretroviral regimen over three-drug regimen was found from the conventional intention-to-treat, dropout-weighted intention-to-treat or per-protocol estimates in the trial sample or target population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1740774518806311","type":"journal-article","created":{"date-parts":[[2018,10,17]],"date-time":"2018-10-17T04:37:06Z","timestamp":1539751026000},"page":"52-62","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["Generalizing the per-protocol treatment effect: The case of ACTG A5095"],"prefix":"10.1177","volume":"16","author":[{"given":"Haidong","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen R","family":"Cole","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H Irene","family":"Hall","sequence":"additional","affiliation":[{"name":"Division of HIV\/AIDS Prevention, National Center for HIV\/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrique F","family":"Schisterman","sequence":"additional","affiliation":[{"name":"Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiffany L","family":"Breger","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessie","family":"K Edwards","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Westreich","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2018,10,17]]},"reference":[{"key":"bibr1-1740774518806311","volume-title":"Clinical trials: a practical approach","author":"Pocock SJ.","year":"1983"},{"key":"bibr2-1740774518806311","volume-title":"Fundamentals of clinical trials","author":"Friedman 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