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The challenges to successful drug development are particularly acute in central nervous system trials such as for pain, schizophrenia, mania, and depression because high\u2010placebo response rates lessen assay sensitivity, diminish estimated treatment effect sizes, and thereby decrease statistical power. This paper addresses the importance of rigorous patient selection in major depressive disorder trials through an enhanced enrichment paradigm. This approach led to a redefinition of an ongoing, blinded phase 3 trial algorithm for patient inclusion (1) to eliminate further randomization of transient placebo responders and (2) to exclude previously randomized transient responders from the primary analysis of the double blind phase of the trial. It is illustrated for a case study for the comparison between brexpiprazole\u00a0+\u00a0antidepressant therapy and placebo\u00a0+\u00a0antidepressant therapy. Analysis of the primary endpoint showed that efficacy of brexpiprazole versus placebo could not be established statistically if the original algorithm for identification of placebo responders was used, but the enhanced enrichment approach did statistically demonstrate efficacy. Additionally, the enhanced enrichment approach identified a target population with a clinically meaningful treatment effect. Through its successful identification of a target population, the innovative enhanced enrichment approach enabled the demonstration of a positive treatment effect in a very challenging area of depression research.<\/jats:p>","DOI":"10.1002\/pst.1839","type":"journal-article","created":{"date-parts":[[2017,11,20]],"date-time":"2017-11-20T03:22:39Z","timestamp":1511148159000},"page":"144-154","source":"Crossref","is-referenced-by-count":1,"title":["A case study in identifying targeted patients population in major depressive disorder by enhanced enrichment design"],"prefix":"10.1002","volume":"17","author":[{"given":"Peter","family":"Zhang","sequence":"first","affiliation":[{"name":"Otsuka Pharmaceutical Development &amp; Commercialization, Inc.  Princeton NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Carroll","sequence":"additional","affiliation":[{"name":"KJC Statistics Ltd.  Bramhall, Cheshire UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary","family":"Hobart","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development &amp; Commercialization, Inc.  Princeton NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carole","family":"Augustine","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development &amp; Commercialization, Inc.  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