{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T07:51:55Z","timestamp":1785829915079,"version":"3.56.0"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T00:00:00Z","timestamp":1718323200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Emulation of the \u201ctarget trial\u201d (TT), a hypothetical pragmatic randomized controlled trial (RCT), using observational data can be used to mitigate issues commonly encountered in comparative effectiveness research (CER) when randomized trials are not logistically, ethically, or financially feasible. However, cardiovascular (CV) health research has been slow to adopt TT emulation. Here, we demonstrate the design and analysis of a TT emulation using electronic health records to study the comparative effectiveness of the addition of a disease-modifying anti-rheumatic drug (DMARD) to a regimen of methotrexate on CV events among rheumatoid arthritis (RA) patients.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We used data from an electronic medical records-based cohort of RA patients from Northwestern Medicine to emulate the TT. Follow-up began 3 months after initial prescription of MTX (2000\u20132020) and included all available follow-up through June 30, 2020. Weighted pooled logistic regression was used to estimate differences in CVD risk and survival. Cloning was used to handle immortal time bias and weights to improve baseline and time-varying covariate imbalance.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>We identified 659 eligible people with RA with average follow-up of 46 months and 31 MACE events. The month 24 adjusted risk difference for MACE comparing initiation vs non-initiation of a DMARD was -1.47% (95% confidence interval [CI]: -4.74, 1.95%), and the marginal hazard ratio (HR) was 0.72 (95% CI: 0.71, 1.23). In analyses subject to immortal time bias, the HR was 0.62 (95% CI: 0.29\u20131.44).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>In this sample, we did not observe evidence of differences in risk of MACE, a finding that is compatible with previously published meta-analyses of RCTs. Thoughtful application of the TT framework provides opportunities to conduct CER in observational data. Benchmarking results of observational analyses to previously published RCTs can lend credibility to interpretation.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0305467","type":"journal-article","created":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T17:29:27Z","timestamp":1718386167000},"page":"e0305467","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Designing target trials using electronic health records: A case study of second-line disease-modifying anti-rheumatic drugs and cardiovascular disease outcomes in patients with rheumatoid arthritis"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2533-0818","authenticated-orcid":true,"given":"Adovich S.","family":"Rivera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob B.","family":"Pierce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjun","family":"Sinha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9047-6437","authenticated-orcid":true,"given":"Anna E.","family":"Pawlowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald M.","family":"Lloyd-Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne C.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Feinstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia C.","family":"Petito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,6,14]]},"reference":[{"key":"pone.0305467.ref001","doi-asserted-by":"crossref","first-page":"367","DOI":"10.7326\/0003-4819-156-5-201203060-00009","article-title":"What comparative effectiveness research is needed? 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Methodological challenges and solutions demonstrated by the DIAMOND-study","volume":"7","author":"GAJ Fransen","year":"2007","journal-title":"BMC Med Res Methodol"},{"key":"pone.0305467.ref033","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1093\/aje\/kww165","article-title":"Targeted maximum likelihood estimation for causal inference in observational studies","volume":"185","author":"MS Schuler","year":"2017","journal-title":"Am J Epidemiol"},{"key":"pone.0305467.ref034","doi-asserted-by":"crossref","unstructured":"WHO Solidarity Trial Consortium. Repurposed Antiviral Drugs for Covid-19\u2014Interim WHO Solidarity Trial Results. 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