{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T02:41:53Z","timestamp":1768876913796,"version":"3.49.0"},"reference-count":20,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T00:00:00Z","timestamp":1618444800000},"content-version":"unspecified","delay-in-days":14,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/N013638\/1"],"award-info":[{"award-number":["MR\/N013638\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2021,2,23]]},"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Patients with atrial fibrillation experience an irregular heart rate and have an increased risk of stroke; prophylactic treatment with anticoagulation medication reduces this risk. Direct-acting oral anticoagulants (DOACs) have been approved providing an alternative to vitamin K antagonists such as warfarin. There is interest from regulatory bodies on the effectiveness of medications in routine clinical practice; however, uncertainty remains regarding the suitability of non-interventional data for answering questions on drug effectiveness and on the most suitable methods to be used. In this study, we will use data from Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE)\u2014the pivotal trial for the DOAC apixaban\u2014to validate non-interventional methods for assessing treatment effectiveness of anticoagulants. These methods could then be applied to analyse treatment effectiveness in people excluded from or under-represented in ARISTOTLE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>Patient characteristics from ARISTOTLE will be used to select a cohort of patients with similar baseline characteristics from two UK electronic health record (EHR) databases, Clinical Practice Research Datalink Gold and Aurum (between 1 January 2013 and 31 July 2019). Methods such as propensity score matching and coarsened exact matching will be explored in matching between EHR treatment groups to determine the optimal method of obtaining a balanced cohort.<\/jats:p>\n                    <jats:p>Absolute and relative risk of outcomes in the EHR trial-analogous cohort will be calculated and compared with the ARISTOTLE results; if results are deemed compatible the methods used for matching EHR treatment groups can then be used to examine drug effectiveness over a longer duration of exposure and in special patient groups of interest not studied in the trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The study has been approved by the Independent Scientific Advisory Committee of the UK Medicines and Healthcare Products Regulatory Agency. Results will be disseminated in scientific publications and at relevant conferences.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2020-042947","type":"journal-article","created":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T14:03:23Z","timestamp":1618495403000},"page":"e042947","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Real-world effects of medications for stroke prevention in atrial fibrillation: protocol for a UK population-based non-interventional cohort study with validation against randomised trial results"],"prefix":"10.1136","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9427-9468","authenticated-orcid":false,"given":"Emma Maud","family":"Powell","sequence":"first","affiliation":[{"name":"Department of Non-communicable Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian J","family":"Douglas","sequence":"additional","affiliation":[{"name":"Department of Non-communicable Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2040-1763","authenticated-orcid":false,"given":"Usha","family":"Gungabissoon","sequence":"additional","affiliation":[{"name":"Epidemiology (Value Evidence and Outcomes), GSK, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liam","family":"Smeeth","sequence":"additional","affiliation":[{"name":"Department of Non-communicable Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Wing","sequence":"additional","affiliation":[{"name":"Department of Non-communicable Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2021,4,15]]},"reference":[{"key":"2025121411544314000_11.4.e042947.1","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2018-312977"},{"key":"2025121411544314000_11.4.e042947.2","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/eus087"},{"key":"2025121411544314000_11.4.e042947.3","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.22.8.983"},{"key":"2025121411544314000_11.4.e042947.4","doi-asserted-by":"publisher","DOI":"10.1161\/hs0901.094253"},{"key":"2025121411544314000_11.4.e042947.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2004.06.003"},{"key":"2025121411544314000_11.4.e042947.6","doi-asserted-by":"publisher","DOI":"10.1007\/s11096-014-0038-3"},{"key":"2025121411544314000_11.4.e042947.7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1107039"},{"key":"2025121411544314000_11.4.e042947.8","unstructured":"U.S. Department of Health and Human Services F and D . Guidance for Industry Postmarketing Studies and Clinical Trials \u2014 Implementation of Section 505(o)(3) of the Federal Food, Drug, and Cosmetic Act"},{"key":"2025121411544314000_11.4.e042947.9","unstructured":"European parliament and the council of the European union . Regulation (EU) NO 1235\/2010 of the European Parliament and of the Council of 15 December, 2010."},{"key":"2025121411544314000_11.4.e042947.10","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2017-019475"},{"key":"2025121411544314000_11.4.e042947.11","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv098"},{"key":"2025121411544314000_11.4.e042947.12","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyz034"},{"key":"2025121411544314000_11.4.e042947.13","doi-asserted-by":"publisher","DOI":"10.1093\/pan\/mpr013"},{"key":"2025121411544314000_11.4.e042947.14","unstructured":"King G , Nielsen R , Coberley C . Comparative effectiveness of matching methods for causal inference. Available: https:\/\/gking.harvard.edu\/publications\/comparative-effectiveness-matching-methods-causal-inference [Accessed 4 Sep 2018]."},{"key":"2025121411544314000_11.4.e042947.15","unstructured":"European Medicines Agency . Committee for medicinal products for human use (CHMP). assessment report Eliquis apixaban. Procedure No.:EMEA\/H\/C\/002148\/X\/04\/G.EMA\/641505\/2012, 2012."},{"key":"2025121411544314000_11.4.e042947.16","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.313.7048.36"},{"key":"2025121411544314000_11.4.e042947.17","doi-asserted-by":"crossref","first-page":"4538","DOI":"10.1002\/sim.8715","article-title":"A tutorial on dealing with time-varying eligibility for treatment: comparing the risk of major bleeding with direct-acting oral anticoagulants vs warfarin","volume":"39","author":"Schnitzer","year":"2020","journal-title":"Stat Med"},{"key":"2025121411544314000_11.4.e042947.18","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k2505"},{"key":"2025121411544314000_11.4.e042947.19","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0148349","article-title":"The impact of the choice of data source in record linkage studies estimating mortality in venous thromboembolism","volume":"11","author":"Gallagher","year":"2016","journal-title":"PLoS One"},{"key":"2025121411544314000_11.4.e042947.20","doi-asserted-by":"publisher","DOI":"10.3399\/bjgp10X483562"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2020-042947","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T19:54:47Z","timestamp":1765742087000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2020-042947"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4]]},"references-count":20,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4,15]]},"published-print":{"date-parts":[[2021,4]]}},"alternative-id":["10.1136\/bmjopen-2020-042947"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2020-042947","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4]]}}}