{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T10:21:29Z","timestamp":1777544489735,"version":"3.51.4"},"reference-count":42,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2009,8,1]],"date-time":"2009-08-01T00:00:00Z","timestamp":1249084800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Trials"],"published-print":{"date-parts":[[2009,8]]},"abstract":"<jats:p>Objective Studies measuring progression of carotid artery intima-media thickness (cIMT) have been used to estimate the effect of lipid-modifying therapies cardiovascular event risk. The likelihood that future cIMT clinical trials will detect a true treatment effect is estimated by leveraging results from prior studies. The present analyses assess the impact of between- and within-study variability based on currently published data from prior clinical studies on the likelihood that ongoing or future cIMT trials will detect the true treatment effect of lipid-modifying therapies.<\/jats:p>\n                  <jats:p>Methods Published data from six contemporary cIMT studies (ASAP, ARBITER 2, RADIANCE 1, RADIANCE 2, ENHANCE, and METEOR) including data from a total of 3563 patients were examined. Bayesian and frequentist methods were used to assess the impact of between study variability on the likelihood of detecting true treatment effects on 1-year cIMT progression\/regression and to provide a sample size estimate that would specifically compensate for the effect of between-study variability.<\/jats:p>\n                  <jats:p>Results In addition to the well-described within-study variability, there is considerable between-study variability associated with the measurement of annualized change in cIMT. Accounting for the additional between-study variability decreases the power for existing study designs. In order to account for the added between-study variability, it is likely that future cIMT studies would require a large increase in sample size in order to provide substantial probability (\u226590%) to have 90% power of detecting a true treatment effect.<\/jats:p>\n                  <jats:p>Limitation Analyses are based on study level data. Future meta-analyses incorporating patient-level data would be useful for confirmation.<\/jats:p>\n                  <jats:p>Conclusion Due to substantial within- and between-study variability in the measure of 1-year change of cIMT, as well as uncertainty about progression rates in contemporary populations, future study designs evaluating the effect of new lipid-modifying therapies on atherosclerotic disease progression are likely to be challenged by large sample sizes in order to demonstrate a true treatment effect.<\/jats:p>","DOI":"10.1177\/1740774509339977","type":"journal-article","created":{"date-parts":[[2009,8,10]],"date-time":"2009-08-10T10:39:53Z","timestamp":1249900793000},"page":"305-319","source":"Crossref","is-referenced-by-count":7,"title":["Effects of sources of variability on sample sizes required for RCTs, applied to trials of lipid-altering therapies on carotid artery intima-media thickness"],"prefix":"10.1177","volume":"6","author":[{"given":"A Lawrence","family":"Gould","sequence":"first","affiliation":[{"name":"Merck Research Laboratories, Rahway, NJ, USA,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joerg","family":"Koglin","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories, Rahway, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raymond P","family":"Bain","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories, Rahway, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cathy-Anne","family":"Pinto","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories, Rahway, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yale B","family":"Mitchel","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories, Rahway, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard C","family":"Pasternak","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories, Rahway, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aditi","family":"Sapre","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories, Rahway, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2009,8,10]]},"reference":[{"key":"atypb1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.628875"},{"key":"atypb2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(02)02957-0"},{"key":"atypb3","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a009302"},{"key":"atypb4","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1056\/NEJM199901073400103","volume":"340","author":"O\u2019Leary DH","year":"1999","journal-title":"N Engl J Med"},{"key":"atypb5","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2004.02.009"},{"key":"atypb6","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehn070"},{"key":"atypb7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0800742"},{"key":"atypb8","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61088-5"},{"key":"atypb9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa071359"},{"key":"atypb10","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000148955.19792.8D"},{"key":"atypb11","doi-asserted-by":"publisher","DOI":"10.1002\/sim.2087"},{"key":"atypb12","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)04053-8"},{"key":"atypb13","doi-asserted-by":"publisher","DOI":"10.1001\/jama.297.12.1344"},{"key":"atypb14","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/31.3-4.362"},{"key":"atypb15","doi-asserted-by":"crossref","unstructured":"Verrill S. 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