{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:12:17Z","timestamp":1791594737241,"version":"4.3.4"},"reference-count":51,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T00:00:00Z","timestamp":1680048000000},"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":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Ideally, the objectives of a pharmacoepidemiologic comparative effectiveness or safety study should dictate its design and data analysis. This paper discusses how defining an estimand is instrumental to this process.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We applied the ICH\u2010E9 (<jats:italic>Statistical Principles for Clinical Trials<\/jats:italic>) R1 addendum on estimands \u2013 which originally focused on randomized trials \u2013 to three examples of observational pharmacoepidemiologic comparative effectiveness and safety studies. Five key elements specify the estimand: the population, contrasted treatments, endpoint, intercurrent events, and population\u2010level summary measure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Different estimands were defined for case studies representing three types of pharmacological treatments: (1) single\u2010dose treatments using a case study about the effect of influenza vaccination versus no vaccination on mortality risk in an adult population of \u226560\u2009years of age; (2) sustained\u2010treatments using a case study about the effect of dipeptidyl peptidase 4 inhibitor versus glucagon\u2010like peptide\u20101 agonist on hypoglycemia risk in treatment of uncontrolled diabetes; and (3) as needed treatments using a case study on the effect of nitroglycerin spray as\u2010needed versus no nitroglycerin on syncope risk in treatment of stabile angina pectoris.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The case studies illustrated that a seemingly clear research question can still be open to multiple interpretations. Defining an estimand ensures that the study targets a treatment effect that aligns with the treatment decision the study aims to inform. Estimand definitions further help to inform choices regarding study design and data\u2010analysis and clarify how to interpret study findings.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.5620","type":"journal-article","created":{"date-parts":[[2023,3,22]],"date-time":"2023-03-22T10:13:10Z","timestamp":1679479990000},"page":"863-872","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Tell me what you want, what you really really want: Estimands in observational pharmacoepidemiologic comparative effectiveness and safety studies"],"prefix":"10.1002","volume":"32","author":[{"given":"Kim","family":"Luijken","sequence":"first","affiliation":[{"name":"Department of Epidemiology Utrecht University Medical Center, University Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rik","family":"van Eekelen","sequence":"additional","affiliation":[{"name":"Centre for Reproductive Medicine, Amsterdam University Medical Center  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helga","family":"Gardarsdottir","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Clinical Pharmacology Utrecht Institute for Pharmaceutical Sciences, Utrecht University  Utrecht The Netherlands"},{"name":"Department of Clinical Pharmacy, Division Laboratories Pharmacy and Biomedical Genetics, University Medical Center Utrecht, Utrecht University  Utrecht The Netherlands"},{"name":"Faculty of Pharmaceutical Sciences, University of Iceland  Reykjavik Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf H. 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