{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T21:07:05Z","timestamp":1774645625274,"version":"3.50.1"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,1,8]],"date-time":"2016-01-08T00:00:00Z","timestamp":1452211200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001826","name":"Netherlands Organisation for Health Research and Development","doi-asserted-by":"publisher","award":["152002040"],"award-info":[{"award-number":["152002040"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>A potentially useful role for instrumental variable (IV) analysis may be as a complementary analysis to assess the presence of confounding when studying adverse drug effects. There has been discussion on whether the observed increased risk of venous thromboembolism (VTE) for third\u2010generation oral contraceptives versus second\u2010generation oral contraceptives could be (partially) attributed to confounding. We investigated how prescribing preference IV estimates compare with conventional estimates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Women in the Clinical Practice Research Database who started a second\u2010generation or third\u2010generation oral contraceptive from 1989 to 2013 were included. Ordinary least squares and two\u2010stage least squares regression were used to estimate risk differences in VTE. Cox regression and IV for Cox proportional hazards regression were used to calculate hazard ratios (HR). The instrument used was the proportion of prescriptions for third\u2010generation oral contraceptives by the general practitioner in the year preceding the current prescription.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All analyses pointed in the direction of an increased VTE risk for third\u2010generation oral contraceptives. The adjusted HR from the conventional Cox regression was 1.62 (95% confidence interval 1.16\u20132.27) and the fully adjusted HR from the IV Cox regression was 3.45 (95% confidence interval; 0.97\u201311.7), showing a larger risk and wider confidence intervals in the IV analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The similarity in direction of results from the IV analyses and conventional analyses suggests that major confounding is unlikely. IV analysis can be a useful complementary analysis to assess the presence of confounding in studies of adverse drug effects in very large databases. Copyright \u00a9 2016 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.3956","type":"journal-article","created":{"date-parts":[[2016,1,10]],"date-time":"2016-01-10T13:04:14Z","timestamp":1452431054000},"page":"317-324","source":"Crossref","is-referenced-by-count":9,"title":["Instrumental variable analysis as a complementary analysis in studies of adverse effects: venous thromboembolism and second\u2010generation versus third\u2010generation oral contraceptives"],"prefix":"10.1002","volume":"25","author":[{"given":"Anna G. 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