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Tramadol, hydrocodone, and codeine depend on the cytochrome P450 2D6 (CYP2D6) enzyme for formation of highly potent metabolites. Individuals with reduced or absent CYP2D6 activity (i.e., intermediate metabolizers [IMs] or poor metabolizers [PMs], respectively) have lower concentrations of potent opioid metabolites and potentially inadequate pain control. The primary objective of this prospective, multicenter, randomized pragmatic trial is to determine the effect of postoperative CYP2D6\u2010guided opioid prescribing on pain control and opioid usage. Up to 2020 participants, age \u22658\u2009years, scheduled to undergo a surgical procedure will be enrolled and randomized to immediate pharmacogenetic testing with clinical decision support (CDS) for CYP2D6 phenotype\u2010guided postoperative pain management (intervention arm) or delayed testing without CDS (control arm). CDS is provided through medical record alerts and\/or a pharmacist consult note. For IMs and PM in the intervention arm, CDS includes recommendations to avoid hydrocodone, tramadol, and codeine. Patient\u2010reported pain\u2010related outcomes are collected 10\u2009days and 1, 3, and 6 months after surgery. The primary outcome, a composite of pain intensity and opioid usage at 10\u2009days postsurgery, will be compared in the subgroup of IMs and PMs in the intervention (\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a0152) versus the control (\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a0152) arm. Secondary end points include prescription pain medication misuse scores and opioid persistence at 6 months. This trial will provide data on the clinical utility of CYP2D6 phenotype\u2010guided opioid selection for improving postoperative pain control and reducing opioid\u2010related risks.\n                  <\/jats:p>","DOI":"10.1111\/cts.13376","type":"journal-article","created":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T03:44:38Z","timestamp":1658979878000},"page":"2479-2492","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Implementing a pragmatic clinical trial to tailor opioids for acute pain on behalf of the\n                    <scp>IGNITE ADOPT PGx<\/scp>\n                    investigators"],"prefix":"10.1111","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7184-5292","authenticated-orcid":false,"given":"Larisa H.","family":"Cavallari","sequence":"first","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine College of Pharmacy, University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Cicali","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine College of Pharmacy, University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Wiisanen","sequence":"additional","affiliation":[{"name":"Department of Community Dentistry and Behavioral Science, College of Dentistry University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger B.","family":"Fillingim","sequence":"additional","affiliation":[{"name":"Department of Community Dentistry and Behavioral Science, College of Dentistry University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hrishikesh","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics Duke University  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel A.","family":"Myers","sequence":"additional","affiliation":[{"name":"Duke Center for Applied Genomics &amp; 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