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However, Mendelian randomization, a genetic tool to test causality of a biomarker, and phase III randomized controlled trials of inhibitors of theses enzymes (varespladib and darapladib) converged to indicate that elevated levels are unlikely to be themselves causal of coronary heart disease and that inhibition had little or no clinical utility. The concordance of findings from Mendelian randomization and clinical trials suggests that for these 2 drugs, and for other novel biomarkers in future, validation of potential therapeutic targets by genetic studies (such as Mendelian randomization) before embarking on costly phase III randomized controlled trials could increase efficiency and offset the high risk of drug development, thereby facilitating discovery of new therapeutics and mitigating against the exuberant costs of drug development.<\/jats:p>","DOI":"10.1161\/atvbaha.115.305234","type":"journal-article","created":{"date-parts":[[2015,9,4]],"date-time":"2015-09-04T03:19:15Z","timestamp":1441336755000},"page":"2281-2289","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":45,"title":["Deciphering the Causal Role of sPLA2s and Lp-PLA2 in Coronary Heart Disease"],"prefix":"10.1161","volume":"35","author":[{"given":"Philippa J.","family":"Talmud","sequence":"first","affiliation":[{"name":"From the Center for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK (P.J.T.); and Clinical Trial Service Unit &amp; Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK (M.V.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael V.","family":"Holmes","sequence":"additional","affiliation":[{"name":"From the Center for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK (P.J.T.); and Clinical Trial Service Unit &amp; Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK (M.V.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.03.016"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1504317"},{"key":"e_1_3_4_4_2","first-page":"6","article-title":"Tufts study finds big rise \u2018in cost of drug development\u2019.","volume":"92","author":"Mullin R","year":"2014","unstructured":"Mullin R. 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