{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T09:24:37Z","timestamp":1770283477803,"version":"3.49.0"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T00:00:00Z","timestamp":1712793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Drug Saf. Regul."],"abstract":"<jats:p>External comparator (EC) studies are increasingly being used to generate evidence that supports the evaluation of emerging pharmacological treatments for regulatory and health technology assessment (HTA) purposes. However, the reliability of evidence generated from EC studies can vary. In this paper, we outline how an existing framework for causal inference, the target trial emulation (TTE) framework, can be appropriately applied to improve the design and analysis of EC studies. Applying the TTE framework involves specifying the protocol of an ideal target trial which would answer the causal question of interest, then emulating its key elements under real-world (RW) settings. We describe each component of the original TTE framework and explain how it can be applied to EC studies, supplemented with practical recommendations. We also highlight special considerations and limitations in applying the TTE framework to EC studies. We describe how the TTE framework can be applied to improve the clarity, transparency, and reliability of evidence generated from EC studies.<\/jats:p>","DOI":"10.3389\/fdsfr.2024.1380568","type":"journal-article","created":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T04:30:09Z","timestamp":1712809809000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Application of the target trial emulation framework to external comparator studies"],"prefix":"10.3389","volume":"4","author":[{"given":"Kellyn","family":"Arnold","sequence":"first","affiliation":[]},{"given":"Luis","family":"Antunes","sequence":"additional","affiliation":[]},{"given":"Briana","family":"Coles","sequence":"additional","affiliation":[]},{"given":"Hopin","family":"Lee","sequence":"additional","affiliation":[]}],"member":"1965","published-online":{"date-parts":[[2024,4,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"100545","DOI":"10.1016\/j.hlpt.2021.100545","article-title":"Analysing electronic health records: the benefits of target trial emulation","volume":"10","author":"Bakker","year":"2021","journal-title":"Health Policy Technol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"e1322","DOI":"10.1212\/WNL.0000000000010433","article-title":"Emulating a target trial of statin use and risk of dementia using cohort data","volume":"95","author":"Caniglia","year":"2020","journal-title":"Neurology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1097\/QAD.0000000000001673","article-title":"Emulating a target trial of antiretroviral therapy regimens started before conception and risk of adverse birth outcomes","volume":"32","author":"Caniglia","year":"2018","journal-title":"AIDS"},{"key":"B4","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1002\/cpt.1586","article-title":"Using electronic health records to derive control arms for early phase single-arm lung cancer trials: proof-of-concept in randomized controlled trials","volume":"107","author":"Carrigan","year":"2020","journal-title":"Clin. 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