{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T21:26:33Z","timestamp":1793568393475,"version":"4.5.0"},"reference-count":42,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"abstract":"<jats:p>Trials that use a randomization process are preferred for evaluating causal effect. However, these interventional studies are not always feasible due to ethical, time, and cost constraints. Additionally, they are often criticized for not accurately representing patients seen in clinical practice. Observational studies can help bridge this gap, but they are often affected by several sources of bias. A growing framework known as target trial emulation (TTE) is increasingly being applied to real-world data to minimize these common biases in observational studies and, under certain conditions, allow for causal interpretation. In this study, we assessed the 5-y effect of thiazide monotherapy, an antihypertensive medication known to cause xerostomia, on the risk of developing dental caries. We applied the target trial framework to build a TTE cohort using an active comparator new user design. We compared thiazide vs nonthiazide monotherapy using electronic health records from the All of Us Research Program. Furthermore, we developed 2 na\u00efve cohorts: a prevalent user cohort, which included existing medication users, and a nonaligned cohort, which was affected by immortal time bias. These cohorts helped illustrate the advantages of TTE. In the TTE cohort, we found no significant difference in the 5-y risk of dental caries between groups, with a risk difference of 0.29% (95% CI, \u22120.36% to 0.95%). In contrast, the na\u00efve cohorts showed directionally opposite effects, with 5-y risk differences of 0.65% (95% CI, 0.22% to 1.09%) in the prevalent user cohort and \u22120.24% (95% CI, \u22120.55% to 0.07%) in the nonaligned cohort, highlighting the impact of design-related biases on the observed outcomes. We demonstrated how the TTE framework can help avoid common biases in observational research, enabling researchers to answer important oral health questions.<\/jats:p>","DOI":"10.1177\/00220345261429938","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T08:11:23Z","timestamp":1773821483000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Target Trial Emulation to Assess Oral Drug Safety"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9788-0118","authenticated-orcid":false,"given":"I.","family":"Leiva-Escobar","sequence":"first","affiliation":[{"name":"Institute of Health Services Research in Dentistry, University of M\u00fcnster, M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7904-8738","authenticated-orcid":false,"given":"A.","family":"Puzhakkara Chennas","sequence":"additional","affiliation":[{"name":"Institute of Health Services Research in Dentistry, University of M\u00fcnster, M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5273-7288","authenticated-orcid":false,"given":"S.L.","family":"Reckelkamm","sequence":"additional","affiliation":[{"name":"Institute of Health Services Research in Dentistry, University of M\u00fcnster, M\u00fcnster, Germany"},{"name":"Clinic for Periodontology and Conservative Dentistry, University of M\u00fcnster, M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Gelberg","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, UCLA David Geffen School of Medicine, University of California, Los Angeles, CA, USA"},{"name":"Department of Health Policy and Management, UCLA Fielding School of Public Health, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9391-6602","authenticated-orcid":false,"given":"S.-E.","family":"Baumeister","sequence":"additional","affiliation":[{"name":"Institute of Health Services Research in Dentistry, University of M\u00fcnster, M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6893-7367","authenticated-orcid":false,"given":"M.","family":"Nolde","sequence":"additional","affiliation":[{"name":"Institute of Health Services Research in Dentistry, University of M\u00fcnster, M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"crossref","unstructured":"Aliko A et al. 2015. 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