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Results from clinical studies and mechanistic understandings suggest that CYP2D6\u2010guided therapy will improve pain control and reduce adverse drug events. However, CYP2D6 is rarely used in clinical practice due in part to the demand for additional clinical trial evidence. Thus, we designed the ADOPT\u2010PGx (A Depression and Opioid Pragmatic Trial in Pharmacogenetics) chronic pain study, a multicenter, pragmatic, randomized controlled clinical trial, to assess the effect of <jats:italic>CYP2D6<\/jats:italic> testing on pain management. The study enrolled 1048 participants who are taking or being considered for treatment with CYP2D6\u2010impacted opioids for their chronic pain. Participants were randomized to receive immediate or delayed (by 6\u2009months) genotyping of <jats:italic>CYP2D6<\/jats:italic> with clinical decision support (CDS). CDS encouraged the providers to follow the CYP2D6\u2010guided trial recommendations. The primary study outcome is the 3\u2010month absolute change in the composite pain intensity score assessed using Patient\u2010Reported Outcomes Measurement Information System (PROMIS) measures. Follow\u2010up will be completed in July 2024. Herein, we describe the design of this trial along with challenges encountered during enrollment.<\/jats:p>","DOI":"10.1111\/cts.70005","type":"journal-article","created":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T12:03:22Z","timestamp":1724414602000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Implementing a pragmatic clinical trial to tailor opioids for chronic pain on behalf of the <scp>IGNITE ADOPT PGx<\/scp> investigators"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3849-374X","authenticated-orcid":false,"given":"Todd C.","family":"Skaar","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0086-8339","authenticated-orcid":false,"given":"Rachel 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