{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T01:59:24Z","timestamp":1755223164520,"version":"3.43.0"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T00:00:00Z","timestamp":1747612800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>In pharmaco\u2010epidemiological studies using vitamin K antagonist (VKA) exposure, constructing treatment episodes based on dispensed prescriptions is challenging, particularly due to the large variability in therapeutic dose.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To validate different methods of constructing VKA treatment episodes based on dispensed prescriptions, using VKA exposure based on international normalized ratio (INR) measurements as a reference.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data from five Dutch anticoagulation clinics were linked to VKA dispensing data from Statistics Netherlands. Three random samples of 10\u2009000 VKA users between 2013 and 2019 were used to compare the construction of VKA treatment episodes based on dispensings, applying fixed or dynamic methods, against the reference of exposure based on INR measurements. A total of 60 different methods were validated by computing the percentage of INR measurements occurring outside dispensing\u2010based VKA treatment episodes, the ratio of VKA\u2010exposed person\u2010time based on dispensings vs. INR measurements, and the number of dispensing\u2010based episodes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Depending on the method used to construct treatment episodes, 14.8%\u201342.2% of the INR measurements were not covered by a dispensing\u2010based episode. The VKA\u2010exposed person\u2010time ratio ranged between 0.73 and 1.13, and there was substantial variability in the number of dispensing\u2010based episodes. Fixed methods resulted in a lower percentage of INR measurements outside the dispensing\u2010based episodes, a VKA\u2010exposed person\u2010time ratio closer to 1.0, and a lower number of constructed episodes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Fixed methods performed better than dynamic methods when classifying VKA exposure based on dispensing data. Our findings may guide other researchers working with VKA dispensing data, especially when the tablets dispensed or the prescribed dose are unavailable.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.70158","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T05:15:06Z","timestamp":1747718106000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Determining Drug Exposure Based on Medication Dispensing Data: A Validation Study of Vitamin K Antagonist Treatment Episodes Against <scp>INR<\/scp> Records"],"prefix":"10.1002","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9458-8674","authenticated-orcid":false,"given":"Eva K.","family":"Kempers","sequence":"first","affiliation":[{"name":"Department of Hematology Erasmus MC, Erasmus University Medical Centre Rotterdam  Rotterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chantal","family":"Visser","sequence":"additional","affiliation":[{"name":"Department of Hematology Erasmus MC, Erasmus University Medical Centre Rotterdam  Rotterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jamilla","family":"Goedegebuur","sequence":"additional","affiliation":[{"name":"Department of Medicine \u2013 Thrombosis and Haemostasis Leiden University Medical Center  Leiden the Netherlands"},{"name":"Department of Clinical Epidemiology Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingui","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mette","family":"S\u00f8gaard","sequence":"additional","affiliation":[{"name":"Danish Center for Health Services Research, Department of Clinical Medicine Aalborg University Hospital, Aalborg University  Aalborg Denmark"},{"name":"Center for General Practice Aalborg University  Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne Gulbech","family":"Ording","sequence":"additional","affiliation":[{"name":"Danish Center for Health Services Research, Department of Clinical Medicine Aalborg University Hospital, Aalborg University  Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carline","family":"van den Dries","sequence":"additional","affiliation":[{"name":"Department of General Practice &amp; Nursing Science Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University  Utrecht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise","family":"Abbel","sequence":"additional","affiliation":[{"name":"Department of Medicine \u2013 Thrombosis and Haemostasis Leiden University Medical Center  Leiden the Netherlands"},{"name":"Department of Gerontology and Geriatrics Leiden University Medical Center  Leiden the Netherlands"},{"name":"LUMC Center for Medicine for Older People LUMC  Leiden the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah J.","family":"Aldridge","sequence":"additional","affiliation":[{"name":"Population Data Science Swansea University  Swansea UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kate J.","family":"Lifford","sequence":"additional","affiliation":[{"name":"Wales Centre for Primary and Emergency Care Research (PRIME Centre Wales), Division of Population Medicine Cardiff University  Cardiff UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanneke E. 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