{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T17:36:28Z","timestamp":1775151388856,"version":"3.50.1"},"reference-count":12,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2004,6,1]],"date-time":"2004-06-01T00:00:00Z","timestamp":1086048000000},"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":["Stat Methods Med Res"],"published-print":{"date-parts":[[2004,6]]},"abstract":"<jats:p> Clinical adverse experience (AE) data are routinely evaluated using between group P values for every AE encountered within each of several body systems. If the P values are reported and interpreted without multiplicity considerations, there is a potential for an excess of false positive findings. Procedures based on confidence interval estimates of treatment effects have the same potential for false positive findings as P value methods. Excess false positive findings can needlessly complicate the safety profile of a safe drug or vaccine. Accordingly, we propose a novel method for addressing multiplicity in the evaluation of adverse experience data arising in clinical trial settings. The method involves a two-step application of adjusted P values based on the Benjamini and Hochberg<jats:sup>1<\/jats:sup> false discovery rate (FDR). Data from three moderate to large vaccine trials are used to illustrate our proposed \u2018Double FDR\u2019 approach, and to reinforce the potential impact of failing to account for multiplicity. This work was in collaboration with the late Professor John W. Tukey who coined the term \u2018Double FDR\u2019. <\/jats:p>","DOI":"10.1191\/0962280204sm363ra","type":"journal-article","created":{"date-parts":[[2018,10,4]],"date-time":"2018-10-04T16:15:55Z","timestamp":1538669755000},"page":"227-238","source":"Crossref","is-referenced-by-count":100,"title":["Use of the false discovery rate for evaluating clinical safety data"],"prefix":"10.1177","volume":"13","author":[{"given":"Devan V","family":"Mehrotra","sequence":"first","affiliation":[{"name":"Merck Research Laboratories, Blue Bell, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph F","family":"Heyse","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories, Blue Bell, PA, USA,"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2004,6,1]]},"reference":[{"key":"atypb1","first-page":"289","volume":"57","author":"Benjamini Y","year":"1995","journal-title":"Journal of the Royal Statistical Society, Series B"},{"key":"atypb2","first-page":"1905","volume":"18","author":"International Conference on Harmonization (ICH) Expert Working Group","year":"1999","journal-title":"Statistics in Medicine"},{"key":"atypb3","volume-title":"Deming Conference","author":"Gould AL."},{"key":"atypb4","first-page":"608","volume":"84","author":"Soric B.","year":"1989","journal-title":"Journal of the American Statistical Association"},{"key":"atypb5","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/73.3.751"},{"key":"atypb6","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/75.4.800"},{"key":"atypb7","volume-title":"False discovery rate control in pairwise comparisons","author":"Benjamini Y","year":"1993"},{"key":"atypb8","doi-asserted-by":"publisher","DOI":"10.1214\/aos\/1013699998"},{"key":"atypb9","volume-title":"Resampling-based multiple testing","author":"Westfall PH","year":"1993"},{"key":"atypb10","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-3758(99)00041-5"},{"key":"atypb11","doi-asserted-by":"publisher","DOI":"10.3102\/10769986024001042"},{"key":"atypb12","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(02)00469-3"}],"container-title":["Statistical Methods in Medical Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1191\/0962280204sm363ra","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1191\/0962280204sm363ra","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:13:25Z","timestamp":1740788005000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1191\/0962280204sm363ra"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,6]]},"references-count":12,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2004,6]]}},"alternative-id":["10.1191\/0962280204sm363ra"],"URL":"https:\/\/doi.org\/10.1191\/0962280204sm363ra","relation":{},"ISSN":["0962-2802","1477-0334"],"issn-type":[{"value":"0962-2802","type":"print"},{"value":"1477-0334","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,6]]}}}