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We present the development and implementation of an online DDI screener to assess interactions during the STRIVE ensitrelvir trial.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The STRIVE Network is conducting a randomized, double-blind, placebo-controlled trial evaluating ensitrelvir's efficacy and safety in hospitalized adults with coronavirus disease 2019 (COVID-19) and lower respiratory tract involvement. DDI guidance was compiled into a database accessed via a web portal where a multidisciplinary team categorized medications as permitted, prohibited, or conditionally permitted. For prohibited medications, washout periods and start\/restart criteria were provided with alternative medication suggestions. Sites could request new medications for addition. After 18 months, a survey was conducted to assess the tool's usefulness.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Version 1 of the DDI screener launched in December 2022 with 615 medications, expanding to 1182 through 6 updates by version 7. In 11 cases, prohibited medications were revised to conditionally permit enrollment after dosage adjustments (antihypertensives, anti-infectives, and psychiatric medications). Anticoagulants, immunosuppressants, and emergency use medications posed the greatest challenges due to trial blinding. With 334 participants enrolled across 150 sites in 13 countries, 117192 screener searches were completed by May 2024. The most searched medication classes were antihypertensive, antibiotics, corticosteroids, and anticoagulants. Sites found the DDI screener most helpful during screening\/enrollment and valued the washout guidance.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>DDI resources for investigational medications like ensitrelvir, with high DDI potential, are crucial for safe conduct of clinical trials. Effective implementation requires a multidisciplinary, iterative approach that incorporates real-time feedback from trial sites.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ofid\/ofaf327","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T13:32:17Z","timestamp":1749648737000},"source":"Crossref","is-referenced-by-count":2,"title":["Implementation of an Online Drug\u2013Drug Interaction Screener for the STRIVE Ensitrelvir Trial for COVID-19"],"prefix":"10.1093","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9894-615X","authenticated-orcid":false,"given":"Joshua P","family":"Havens","sequence":"first","affiliation":[{"name":"University of Nebraska Medical Center, College of Medicine, Department of Infectious Diseases , Omaha, Nebraska ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nayon","family":"Kang","sequence":"additional","affiliation":[{"name":"Medical Science and Computing\/Guidehouse in Support of National Institute of Allergy and Infectious Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Chung","sequence":"additional","affiliation":[{"name":"CAMRIS International (Under Contract No. 75N93019D00025 with National Institute of Allergy and Infectious Diseases, NIH, DHHS)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3703-7849","authenticated-orcid":false,"given":"Courtney V","family":"Fletcher","sequence":"additional","affiliation":[{"name":"University of Nebraska Medical Center, College of Pharmacy, Department of Pharmacy Practice , Omaha, Nebraska ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2803-4264","authenticated-orcid":false,"given":"Page","family":"Crew","sequence":"additional","affiliation":[{"name":"National Institute of Allergy and Infectious Diseases, National Institute of Health , Bethesda, Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Nordwall","sequence":"additional","affiliation":[{"name":"University of Minnesota, School of Public Health, Division of Biostatistics and Health Data Science , Minneapolis, Minnesota ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9440-9146","authenticated-orcid":false,"given":"Lianne","family":"Siegel","sequence":"additional","affiliation":[{"name":"University of Minnesota, School of Public Health, Division of Biostatistics and Health Data Science , Minneapolis, Minnesota ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina","family":"Harper","sequence":"additional","affiliation":[{"name":"University of Minnesota, School of Public Health, Division of Biostatistics and Health Data Science , Minneapolis, Minnesota ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Grund","sequence":"additional","affiliation":[{"name":"University of Minnesota, College of Liberal Arts, School of Statistics , Minneapolis, Minnesota ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo","family":"Losso","sequence":"additional","affiliation":[{"name":"CICAL and Hospital J.M. 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