{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:40:38Z","timestamp":1792453238401,"version":"4.5.0"},"reference-count":20,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000041","name":"American Diabetes Association","doi-asserted-by":"publisher","award":["1-25-PDF-96"],"award-info":[{"award-number":["1-25-PDF-96"]}],"id":[{"id":"10.13039\/100000041","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Diabetes and Digestive and Kidney Disease","award":["F32-DK-143-609"],"award-info":[{"award-number":["F32-DK-143-609"]}]},{"name":"National Institute on Aging of the National Institutes of Health","award":["R01AG056479"],"award-info":[{"award-number":["R01AG056479"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We described how to adapt the prevalent new-user (PNU) study design to estimate the effect of drug discontinuation among patients who discontinue and clone-censor-weighting (CCW) approach to estimate the effect of drug discontinuation among an eligible population at a pre-specified time point, focusing on the differences between the target trials the 2 approaches emulate. While both approaches produced unbiased estimates of the effect of drug discontinuation when all confounders were adjusted for in simulations, the true estimands differed, particularly when treatment effect heterogeneity was introduced. We also applied the approaches to study the effect of statin discontinuation among United States Medicare beneficiaries who discontinued statin therapy after at least 5\u00a0years (PNU) or at approximately 5\u00a0years (CCW) of continuous use. The PNU analysis estimated a mortality rate difference (MRD) of 3.6 (95% CI, 3.3-3.9) per 100 person-years and a mortality rate ratio (MRR) of 1.41 (95% CI, 1.37-1.45), while the CCW analysis estimated a MRD of 3.4 (95% CI, 2.8-4.0) per 100 person-years and MRR of 1.55 (1.45-1.66). Researchers studying drug discontinuation should carefully consider their causal question and target population when choosing between these 2 newer approaches.<\/jats:p>","DOI":"10.1093\/aje\/kwag238","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T11:15:58Z","timestamp":1790334958000},"source":"Crossref","is-referenced-by-count":0,"title":["Adapting the prevalent new-user study design and clone-censor-weighting approach to evaluate drug discontinuation"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6427-1032","authenticated-orcid":false,"given":"Qoua","family":"Her","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill , 135 Dauer Drive, Chapel Hill, NC 27599 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9204-7177","authenticated-orcid":false,"given":"Til","family":"St\u00fcrmer","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill , 135 Dauer Drive, Chapel Hill, NC 27599 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J","family":"Glynn","sequence":"additional","affiliation":[{"name":"Department of Medicine, Brigham and Women's Hospital , 75 Francis Street, Boston, MA 02115 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Duchesneau","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest University School of Medicine , 475 Vine Street, Winston-Salem, NC 27101 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0980-8896","authenticated-orcid":false,"given":"Tiansheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Health Outcomes and Policy, College of Pharmacy, University of Houston , 4349 Martin Luther King Boulevard, Houston, TX 77204-5047 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Poole","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill , 135 Dauer Drive, Chapel Hill, NC 27599 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1108-0689","authenticated-orcid":false,"given":"Jennifer Leigh","family":"Lund","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill , 135 Dauer Drive, Chapel Hill, NC 27599 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Webster-Clark","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest University School of Medicine , 475 Vine Street, Winston-Salem, NC 27101 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"issue":"9","key":"2026101919065356400_ref1","doi-asserted-by":"publisher","first-page":"2487","DOI":"10.1111\/jgs.17894","article-title":"Recommendations for outcome measurement for deprescribing intervention studies","volume":"70","author":"Bayliss","year":"2022","journal-title":"J Am Geriatr Soc"},{"issue":"2","key":"2026101919065356400_ref2","doi-asserted-by":"publisher","first-page":"2269","DOI":"10.1016\/j.sapharm.2021.05.007","article-title":"Methods for evaluating the benefit and harms of deprescribing in observational research using routinely collected data","volume":"18","author":"Moriarty","year":"2022","journal-title":"Res Social Adm Pharm"},{"issue":"25","key":"2026101919065356400_ref3","doi-asserted-by":"publisher","first-page":"1878","DOI":"10.1056\/NEJM200006223422506","article-title":"A comparison of observational studies and randomized, controlled trials","volume":"342","author":"Benson","year":"2000","journal-title":"N Engl J Med"},{"issue":"2","key":"2026101919065356400_ref4","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.jval.2022.07.003","article-title":"Can observational analyses of routinely collected data emulate randomized trials? Design and feasibility of the observational patient evidence for regulatory approval science and understanding disease project","volume":"26","author":"Crown","year":"2022","journal-title":"Value Health"},{"issue":"4","key":"2026101919065356400_ref5","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1002\/pds.4107","article-title":"Prevalent new-user cohort designs for comparative drug effect studies by time-conditional propensity scores","volume":"26","author":"Suissa","year":"2017","journal-title":"Pharmacoepidemiol Drug Saf"},{"issue":"12","key":"2026101919065356400_ref6","doi-asserted-by":"publisher","DOI":"10.1002\/pds.70048","article-title":"Core concepts in pharmacoepidemiology: new-user designs","volume":"33","author":"Her","year":"2024","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"2026101919065356400_ref7","doi-asserted-by":"publisher","first-page":"kwag227","DOI":"10.1093\/aje\/kwag227","article-title":"Comparing causal estimands from sequential nested versus single point target trials: a simulation study","author":"Wiener","year":"2026","journal-title":"Am J Epidemiol."},{"key":"2026101919065356400_ref8","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k182","article-title":"How to estimate the effect of treatment duration on survival outcomes using observational data","volume":"360","author":"Hern\u00e1n","year":"2018","journal-title":"Bmj"},{"issue":"5","key":"2026101919065356400_ref9","doi-asserted-by":"publisher","first-page":"1719","DOI":"10.1093\/ije\/dyaa057","article-title":"Reflection on modern methods: trial emulation in the presence of immortal-time bias. Assessing the benefit of major surgery for elderly lung cancer patients using observational data","volume":"49","author":"Maringe","year":"2020","journal-title":"Int J Epidemiol"},{"issue":"2","key":"2026101919065356400_ref10","doi-asserted-by":"publisher","first-page":"7","DOI":"10.2202\/1557-4679.1203","article-title":"An introduction to causal inference","volume":"6","author":"Pearl","year":"2010","journal-title":"Int J Biostat"},{"issue":"11","key":"2026101919065356400_ref11","doi-asserted-by":"publisher","first-page":"3567","DOI":"10.1111\/jgs.19093","article-title":"Discontinuation versus continuation of statins: a systematic review","volume":"72","author":"Peixoto","year":"2024","journal-title":"J Am Geriatr Soc"},{"issue":"1","key":"2026101919065356400_ref12","doi-asserted-by":"publisher","DOI":"10.1111\/eci.70126","article-title":"Target trial emulation of statin discontinuation in multimorbid older adults with polypharmacy","volume":"56","author":"Aponte Ribero","year":"2026","journal-title":"Eur J Clin Invest"},{"issue":"6","key":"2026101919065356400_ref13","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.13186","article-title":"Cardiovascular outcomes and mortality associated with discontinuing statins in older patients receiving polypharmacy","volume":"4","author":"Rea","year":"2021","journal-title":"JAMA Netw Open"},{"issue":"12","key":"2026101919065356400_ref14","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.36802","article-title":"Statin discontinuation and cardiovascular events among older people in Denmark","volume":"4","author":"Thompson","year":"2021","journal-title":"JAMA Netw Open"},{"issue":"6","key":"2026101919065356400_ref15","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1097\/00001648-200111000-00017","article-title":"Paradoxical relations of drug treatment with mortality in older persons","volume":"12","author":"Glynn","year":"2001","journal-title":"Epidemiology"},{"issue":"3","key":"2026101919065356400_ref16","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1097\/EDE.0b013e31828ac9cb","article-title":"Case-crossover studies of therapeutics: design approaches to addressing time-varying prognosis in elderly populations","volume":"24","author":"Wang","year":"2013","journal-title":"Epidemiology"},{"issue":"5","key":"2026101919065356400_ref17","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1001\/jamainternmed.2015.0289","article-title":"Safety and benefit of discontinuing statin therapy in the setting of advanced, life-limiting illness: a randomized clinical trial","volume":"175","author":"Kutner","year":"2015","journal-title":"JAMA Intern Med"},{"issue":"24","key":"2026101919065356400_ref18","doi-asserted-by":"publisher","first-page":"2414","DOI":"10.1001\/jama.2019.8145","article-title":"Effect of 1-month dual antiplatelet therapy followed by clopidogrel vs 12-month dual antiplatelet therapy on cardiovascular and bleeding events in patients receiving PCI: the STOPDAPT-2 randomized clinical trial","volume":"321","author":"Watanabe","year":"2019","journal-title":"Jama"},{"issue":"10","key":"2026101919065356400_ref19","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2025-100894","article-title":"Effects of deprescribing from inhaled corticosteroids in people with cystic fibrosis: protocol for a target trial emulation using the UK CF registry","volume":"15","author":"McClenaghan","year":"2025","journal-title":"BMJ Open"},{"key":"2026101919065356400_ref20","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2025-084909","article-title":"Starting right: aligning eligibility and treatment assignment at time zero when emulating a target trial","volume":"392","author":"Fu","year":"2026","journal-title":"Bmj"}],"container-title":["American Journal of Epidemiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/aje\/advance-article-pdf\/doi\/10.1093\/aje\/kwag238\/71606338\/kwag238.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/aje\/advance-article-pdf\/doi\/10.1093\/aje\/kwag238\/71606338\/kwag238.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:06:57Z","timestamp":1792451217000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/aje\/advance-article\/doi\/10.1093\/aje\/kwag238\/8865293"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,5]]},"references-count":20,"URL":"https:\/\/doi.org\/10.1093\/aje\/kwag238","relation":{},"ISSN":["0002-9262","1476-6256"],"issn-type":[{"value":"0002-9262","type":"print"},{"value":"1476-6256","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,5]]},"article-number":"kwag238"}}