{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T17:04:42Z","timestamp":1778691882926,"version":"3.51.4"},"reference-count":22,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T00:00:00Z","timestamp":1723075200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Clinical Trials"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:p>Composite time-to-event endpoints are commonly used in cardiovascular outcome trials. For example, the IMPROVE-IT trial comparing ezetimibe+simvastatin to placebo+simvastatin in 18,144 patients with acute coronary syndrome used a primary composite endpoint with five component outcomes: (1) cardiovascular death, (2) non-fatal stroke, (3) non-fatal myocardial infarction, (4) coronary revascularization \u226530\u2009days after randomization, and (5) unstable angina requiring hospitalization. In such settings, the traditional analysis compares treatments using the observed time to the occurrence of the first (i.e. earliest) component outcome for each patient. This approach ignores information for subsequent outcome(s), possibly leading to reduced power to demonstrate the benefit of the test versus the control treatment. We use real data examples and simulations to contrast the traditional approach with several alternative approaches that use data for all the intra-patient component outcomes, not just the first.<\/jats:p>","DOI":"10.1177\/17407745241267999","type":"journal-article","created":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T00:55:32Z","timestamp":1723164932000},"page":"576-583","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Analysis of composite time-to-event endpoints in cardiovascular outcome trials"],"prefix":"10.1177","volume":"21","author":[{"given":"Rachel","family":"Marceau West","sequence":"first","affiliation":[{"name":"Clinical Biostatistics, Merck & Co., Inc., North Wales, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory","family":"Golm","sequence":"additional","affiliation":[{"name":"Clinical Biostatistics, Merck & Co., Inc., North Wales, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0316-7362","authenticated-orcid":false,"given":"Devan V","family":"Mehrotra","sequence":"additional","affiliation":[{"name":"Clinical Biostatistics, Merck & Co., Inc., North Wales, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2024,8,8]]},"reference":[{"key":"bibr1-17407745241267999","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1410489"},{"key":"bibr2-17407745241267999","doi-asserted-by":"publisher","DOI":"10.1214\/aos\/1176345976"},{"key":"bibr3-17407745241267999","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/68.2.373"},{"key":"bibr4-17407745241267999","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr352"},{"key":"bibr5-17407745241267999","doi-asserted-by":"publisher","DOI":"10.1111\/biom.12225"},{"key":"bibr6-17407745241267999","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/kxv032"},{"key":"bibr7-17407745241267999","doi-asserted-by":"publisher","DOI":"10.1002\/sim.7284"},{"key":"bibr8-17407745241267999","doi-asserted-by":"publisher","DOI":"10.2307\/2529826"},{"key":"bibr9-17407745241267999","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-7152(02)00310-3"},{"key":"bibr10-17407745241267999","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw438"},{"key":"bibr11-17407745241267999","volume-title":"The American soldier: combat and its aftermath (Studies in social psychology in World War II)","author":"Stouffer SA","year":"1949"},{"key":"bibr12-17407745241267999","doi-asserted-by":"publisher","DOI":"10.1037\/0033-2909.97.2.334"},{"key":"bibr13-17407745241267999","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1984.10478093"},{"key":"bibr14-17407745241267999","doi-asserted-by":"publisher","DOI":"10.1177\/1740774515601027"},{"key":"bibr15-17407745241267999","doi-asserted-by":"publisher","DOI":"10.1056\/EVIDoa2200047"},{"key":"bibr16-17407745241267999","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1200933"},{"key":"bibr17-17407745241267999","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1706444"},{"key":"bibr18-17407745241267999","doi-asserted-by":"publisher","DOI":"10.2307\/2530374"},{"key":"bibr19-17407745241267999","doi-asserted-by":"publisher","DOI":"10.1080\/19466315.2021.1895883"},{"key":"bibr20-17407745241267999","doi-asserted-by":"publisher","DOI":"10.1177\/09622802241236934"},{"key":"bibr21-17407745241267999","doi-asserted-by":"publisher","DOI":"10.1002\/sim.8750"},{"key":"bibr22-17407745241267999","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.033065"}],"container-title":["Clinical Trials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17407745241267999","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/17407745241267999","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17407745241267999","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:29:06Z","timestamp":1777397346000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/17407745241267999"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,8]]},"references-count":22,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10.1177\/17407745241267999"],"URL":"https:\/\/doi.org\/10.1177\/17407745241267999","relation":{},"ISSN":["1740-7745","1740-7753"],"issn-type":[{"value":"1740-7745","type":"print"},{"value":"1740-7753","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,8]]}}}