{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:02:49Z","timestamp":1789657369931,"version":"4.0.1"},"reference-count":18,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100002429","name":"Amgen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002429","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Studies comparing treatment strategies based on initiation timing\u2014such as starting PCSK9 inhibitor (PCSK9i) therapy sooner versus later after a myocardial infarction (MI)\u2014are prone to immortal time bias. Clone\u2010censor\u2010weight methods can address these issues and allow the researcher to emulate a trial in which patients are assigned to protocols dictating when PCSK9i is initiated. This study aimed to evaluate the comparability of patients in a clone\u2010censor\u2010weight setup who initiated a PCSK9i within 12\u2009months post\u2010MI versus non\u2010initiators.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We included adult patients hospitalized for MI in Sweden (2015\u20132021) and followed them for 3\u2009years. We considered two treatment strategies: initiating PCSK9i within 12\u2009months versus not initiating PCSK9i during the same period. We applied the clone\u2010censor\u2010weight method to address immortal time bias and assessed remaining bias using covariate balance metrics and negative control outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The primary study sample included 38\u2009\u2009627 episodes of MI, with 561 (1.5%) initiating PCSK9i treatment within 12\u2009months. These patients were younger, had higher baseline LDL\u2010C levels, and were more frequently treated with ezetimibe during their post\u2010MI follow\u2010up compared to non\u2010initiators. Although clone\u2010censor\u2010weight estimation was free of immortal time bias, it faced challenges in achieving adequate balance of covariates due to the high rates of censoring (relatively small number of people initiating a PCSK9i in the first year) and strong association between covariates and censoring. Truncation of weights provided more stable estimates but at the expense of some covariate imbalances.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The clone\u2010censor\u2010weight method is a promising approach that allows researchers to answer questions about the effect of treatment policies. But practical guidance is needed to address problems that arise from small, highly imbalanced groups, which is common with most newly introduced treatments.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pds.70354","type":"journal-article","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T06:12:00Z","timestamp":1774678320000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Methodological Challenges of Emulating a Target Trial to Assess Effectiveness of Timing of\n                    <scp>PCSK9<\/scp>\n                    Inhibitor Treatment Initiation Post Myocardial Infarction"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0912-8226","authenticated-orcid":false,"given":"Thomas","family":"Cars","sequence":"first","affiliation":[{"name":"Sence Research AB  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5894-0351","authenticated-orcid":false,"given":"Stefan","family":"Gustafsson","sequence":"additional","affiliation":[{"name":"Sence Research AB  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9278-230X","authenticated-orcid":false,"given":"Queenie","family":"Chan","sequence":"additional","affiliation":[{"name":"Amgen Ltd, Center for Observational Research  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3204-1328","authenticated-orcid":false,"given":"Nafeesa","family":"Dhalwani","sequence":"additional","affiliation":[{"name":"Amgen Inc, Center for Observational Research  Thousand Oaks California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2891-4520","authenticated-orcid":false,"given":"Shia T.","family":"Kent","sequence":"additional","affiliation":[{"name":"Amgen Inc, Center for Observational Research  Thousand Oaks California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0777-1997","authenticated-orcid":false,"given":"Andrew","family":"Briggs","sequence":"additional","affiliation":[{"name":"London School of Hygiene &amp; Tropical Medicine  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4732-382X","authenticated-orcid":false,"given":"Chris P.","family":"Gale","sequence":"additional","affiliation":[{"name":"School of Medicine University of Leeds  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2573-7239","authenticated-orcid":false,"given":"Anselm","family":"Gitt","sequence":"additional","affiliation":[{"name":"Department of Cardiology Herzzentrum Ludwigshafen  Ludwigshafen am Rhein Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3246-8359","authenticated-orcid":false,"given":"J. Wouter","family":"Jukema","sequence":"additional","affiliation":[{"name":"Department of Cardiology Leiden University Medical Center  the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6896-2941","authenticated-orcid":false,"given":"Philippe Gabriel","family":"Steg","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris\u2010Cit\u00e9, INSERM_1148  Paris France"},{"name":"AP\u2010HP, H\u00f4pital Bichat  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2247-8454","authenticated-orcid":false,"given":"Johan","family":"Sundstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4413-9736","authenticated-orcid":false,"given":"Stefan","family":"James","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Uppsala University  Uppsala Sweden"},{"name":"Uppsala Clinical Research Center Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3221-0144","authenticated-orcid":false,"given":"Emil","family":"Hagstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Uppsala University  Uppsala Sweden"},{"name":"Uppsala Clinical Research Center Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1572-0564","authenticated-orcid":false,"given":"M. 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