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Traditional DDI assessments often do not fully capture complex co\u2010medication patterns observed in real\u2010world practice due to the risk of introducing confounding factors. This study used U.S. Optum claims data from 2019 to 2024 to characterize co\u2010medication patterns in predominately non\u2010small cell lung cancer (NSCLC) patients and map enzyme\u2010 and transporter\u2010mediated liabilities across commonly used medications, chemotherapy agents, and biomarker\u2010driven therapies. Potential DDI liabilities were further prioritized using a semi\u2010quantitative clinical framework based on perpetrator strength, substrate sensitivity, narrow therapeutic index status, and available evidence. Frequently used medications included disease\u2010specific supportive therapies such as ondansetron and dexamethasone, as well as treatments for common U.S. comorbidities such as cardiovascular and endocrine disorders. Many of the co\u2010medications were substrates, inhibitors, and inducers of pathways critical for NSCLC treatments such as CYP3A, CYP2D6, P\u2010gp, and OATP1B and additional risks were identified when giving treatments with acid\u2010reducing agents or QT\u2010prolonging drugs. These findings demonstrate how integrating real\u2010world data (RWD) can strengthen DDI assessment by improving clinical trial design, informing risk\u2010mitigation strategies, and supporting more patient\u2010centric drug development.<\/jats:p>","DOI":"10.1111\/cts.70734","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:45:43Z","timestamp":1790765143000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From Real World Data to Real Impact: A Co\u2010Medication Framework for Lung Cancer to Advance\n                    <scp>DDI<\/scp>\n                    Assessment and Patient\u2010Centric Drug Development"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7842-567X","authenticated-orcid":false,"given":"Mareena","family":"Biju","sequence":"first","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc  Ridgefield Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0319-910X","authenticated-orcid":false,"given":"HeeJae","family":"Choi","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc  Ridgefield Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2945-3695","authenticated-orcid":false,"given":"Shilpa","family":"Madari","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc  Ridgefield Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6218-0997","authenticated-orcid":false,"given":"Annie","family":"Carlisle","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc  Ridgefield Connecticut USA"},{"name":"Astellas Pharma US  Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2236-3032","authenticated-orcid":false,"given":"Ashish","family":"Sharma","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc  Ridgefield Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9483-2355","authenticated-orcid":false,"given":"Christina","family":"Kunz","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH &amp; Co. 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