{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T03:23:39Z","timestamp":1778815419350,"version":"3.51.4"},"reference-count":40,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["UM1 AI068636"],"award-info":[{"award-number":["UM1 AI068636"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["UM1 AI106071"],"award-info":[{"award-number":["UM1 AI106071"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["UM1AI068634"],"award-info":[{"award-number":["UM1AI068634"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Clinical Trials"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Evaluation of heterogeneity of treatment effect among participants in large randomized clinical trials may provide insights as to the value of individualizing clinical decisions. The effect modeling approach to predictive heterogeneity of treatment effect analysis offers a promising framework for heterogeneity of treatment effect estimation by simultaneously considering multiple patient characteristics and their interactions with treatment to predict differences in outcomes between randomized treatments. However, its implementation in clinical research remains limited and so we provide a detailed example of its application in a randomized trial that compared raltegravir-based vs darunavir\/ritonavir-based therapy as initial antiretroviral treatments for people living with HIV.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The heterogeneity of treatment effect analysis used a two-step procedure, in which a working proportional hazards model was first selected to construct an index score for ranking the treatment difference for individuals, and then a second calibration step used a non-parametric kernel approach to estimate the true treatment difference for participants with similar index scores. Sensitivity and supplemental analyses were conducted to evaluate the robustness of the results. We further explored the impact of covariates on heterogeneity of treatment effect and the choice between treatments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The heterogeneity of treatment effect analysis showed that while there is a clear trend favoring raltegravir-based therapy over darunavir\/ritonavir-based therapy for the vast majority of the target population, there were a small subset of patients, characterized by more advanced HIV disease status, for whom the choice between the two treatments might be equivocal.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Through this example, we illustrate how an exploratory heterogeneity of treatment effect analysis might provide further insights into the comparative efficacy of treatments evaluated in a randomized trial. We also highlight some of the issues in implementing and interpreting effect modeling analyses in randomized trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17407745251338558","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T03:14:04Z","timestamp":1747883644000},"page":"559-570","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Precision medicine evaluation of heterogeneity of treatment effect for a time-to-event outcome with application in a trial of Initial treatment for people living with HIV"],"prefix":"10.1177","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0980-5282","authenticated-orcid":false,"given":"Yu","family":"Zheng","sequence":"first","affiliation":[{"name":"Center for Biostatistics in AIDS Research, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judy S","family":"Currier","sequence":"additional","affiliation":[{"name":"Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael D","family":"Hughes","sequence":"additional","affiliation":[{"name":"Center for Biostatistics in AIDS Research, Department of Biostatistics, Harvard T.H. 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