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Finding single nucleotide polymorphisms (SNPs) that are predictive of differential treatment efficacy, measured by a clinical outcome, is fundamentally different and more challenging than the traditional association test for a quantitative trait. With the objective to confidently identify and infer genetic subgroups with enhanced treatment efficacy from a large RCT for an eye disease, age\u2010related macular degeneration (AMD), where the clinical endpoint is binary (progressed or not), we propose a novel SNP\u2010testing procedure for binary clinical outcomes. Specifically, we formulate four contrasts to simultaneously assess all possible genetic effects on a logic\u2010respecting efficacy measure, the relative risk (between treatment and control). Our method controls both within\u2010 and across\u2010SNP multiplicity rigorously. We then use real genotype data to perform chromosome\u2010wide simulations to evaluate our method performance and to provide practical recommendations. Finally, we apply the proposed method to perform a genome\u2010wide SNP testing for the AMD trial and successfully identify multiple gene regions with genetic subgroups exhibiting enhanced efficacy in terms of decreasing the AMD progression\u00a0rate.<\/jats:p>","DOI":"10.1002\/bimj.202000170","type":"journal-article","created":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T07:48:10Z","timestamp":1615362490000},"page":"256-271","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Confident identification of subgroups from SNP testing in RCTs with binary outcomes"],"prefix":"10.1002","volume":"64","author":[{"given":"Yue","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Biostatistics University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinjun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily Y.","family":"Chew","sequence":"additional","affiliation":[{"name":"National Eye Institute NIH  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1352-1000","authenticated-orcid":false,"given":"Ying","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Biostatistics University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,3,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-2456(99)00031-8"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12874-018-0519-5"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2013.01.021"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1214\/17-AOAS1128"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.6822"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3579"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2578"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3448"},{"key":"e_1_2_8_10_1","unstructured":"Genz A. 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