{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T23:44:13Z","timestamp":1789947853626,"version":"4.0.1"},"reference-count":22,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T00:00:00Z","timestamp":1654128000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["1UL1TR003167-01"],"award-info":[{"award-number":["1UL1TR003167-01"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"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>The single patient (n-of-1) trial can be used to resolve therapeutic uncertainty for the individual patient. Treatment alternatives are systematically tested against each other, generating patient-specific data used to inform an individualized treatment plan. We hypothesize that clinical decisions informed by n-of-1 trials improve patient outcomes compared to usual care. Our objective was to provide an overview of the clinical trial evidence on the effect of n-of-1 trials on clinical outcomes.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>A systematic search of medical databases, trial registries, and gray literature was performed to identify trials assessing clinical outcomes in a group of patients undergoing an n-of-1 trial compared to those receiving usual care for any clinical condition. We abstracted elements related to study design and results and assessed risk of bias for both the overall randomized trials and the n-of-1 trials. The review was registered on PROSPERO. (CRD: 42020166490).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Findings<\/jats:title>\n<jats:p>Twelve randomized trials of the n-of-1 approach were identified in conditions spanning chronic pain, osteoarthritis, chronic irreversible airflow limitation, attention-deficit hyperactivity disorder, hyperlipidemia, atrial fibrillation, statin intolerance, and hypertension. One trial showed a statistically significant benefit in the primary outcome. Only one reached the pre-specified sample size target. Secondary outcomes showed modest benefits, including decreasing medication use, fewer atrial fibrillation episodes, and improved patient satisfaction.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Interpretation<\/jats:title>\n<jats:p>Very few trials have been undertaken to assess the effectiveness of n-of-1 trials in improving clinical outcomes, and most trials were underpowered for the primary outcome. Barriers to enrollment and retention in these trials should be explored, as well-powered randomized trials are needed to clarify the clinical impact of n-of-1 trials and assess their utility in clinical practice.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0269387","type":"journal-article","created":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T17:38:59Z","timestamp":1654191539000},"page":"e0269387","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["A scoping review of randomized trials assessing the impact of n-of-1 trials on clinical outcomes"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1552-9025","authenticated-orcid":true,"given":"Joyce P.","family":"Samuel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan H.","family":"Wootton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7212-1704","authenticated-orcid":true,"given":"Travis","family":"Holder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald","family":"Molony","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,6,2]]},"reference":[{"issue":"6","key":"pone.0269387.ref001","first-page":"497","article-title":"A clinician\u2019s guide for conducting randomized trials in individual patients.","volume":"139","author":"G Guyatt","year":"1988","journal-title":"CMAJ"},{"issue":"14","key":"pone.0269387.ref002","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1056\/NEJM198604033141406","article-title":"Determining optimal therapy\u2014randomized trials in individual patients","volume":"314","author":"G Guyatt","year":"1986","journal-title":"N Engl J Med"},{"issue":"8","key":"pone.0269387.ref003","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1097\/MLR.0b013e318215d90d","article-title":"N-of-1 trials in the medical literature: a systematic review.","volume":"49","author":"NB Gabler","year":"2011","journal-title":"Med Care"},{"issue":"9","key":"pone.0269387.ref004","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1093\/abm\/kax026","article-title":"N-of-1 Randomized Intervention Trials in Health Psychology: A Systematic Review and Methodology Critique.","volume":"52","author":"JA Shaffer","year":"2018","journal-title":"Ann Behav Med."},{"issue":"7","key":"pone.0269387.ref005","doi-asserted-by":"crossref","first-page":"467","DOI":"10.7326\/M18-0850","article-title":"PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation.","volume":"169","author":"AC Tricco","year":"2018","journal-title":"Ann Intern 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Shamseer","year":"2015","journal-title":"J Clin Epidemiol."},{"issue":"6","key":"pone.0269387.ref010","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1093\/jpepsy\/18.6.717","article-title":"Methods of evaluating methylphenidate in children with attention deficit hyperactivity disorder: acceptability, satisfaction, and compliance","volume":"18","author":"C Johnston","year":"1993","journal-title":"J Pediatr Psychol"},{"key":"pone.0269387.ref011","volume-title":"N-of-1 Trials In Children With Hypertension (NICHE).","author":"JP Samuel","year":"2018"},{"issue":"10","key":"pone.0269387.ref012","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1001\/jamainternmed.2018.3981","article-title":"Effect of Mobile Device-Supported Single-Patient Multi-crossover Trials on Treatment of Chronic Musculoskeletal Pain: A Randomized Clinical Trial.","volume":"178","author":"RL Kravitz","year":"2018","journal-title":"JAMA Intern Med"},{"issue":"1","key":"pone.0269387.ref013","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1007\/s11606-019-05303-0","article-title":"Effect of Mobile Device-Assisted N-of-1 Trial Participation on Analgesic Prescribing for Chronic Pain: Randomized Controlled Trial.","volume":"35","author":"DD Odineal","year":"2020","journal-title":"J Gen Intern Med"},{"issue":"1","key":"pone.0269387.ref014","first-page":"140","article-title":"The efficacy and cost effectiveness of N of 1 studies with diclofenac compared to standard treatment with nonsteroidal antiinflammatory drugs in osteoarthritis","volume":"31","author":"JE Pope","year":"2004","journal-title":"J Rheumatol"},{"issue":"7038","key":"pone.0269387.ref015","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1136\/bmj.312.7038.1069","article-title":"Randomised study of n of 1 trials versus standard practice","volume":"312","author":"J Mahon","year":"1996","journal-title":"BMJ"},{"issue":"1","key":"pone.0269387.ref016","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1378\/chest.115.1.38","article-title":"Theophylline for irreversible chronic airflow limitation: a randomized study comparing n of 1 trials to standard practice.","volume":"115","author":"JL Mahon","year":"1999","journal-title":"Chest"},{"issue":"2","key":"pone.0269387.ref017","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s12402-012-0099-x","article-title":"Parents\u2019 attitudes toward methylphenidate using n-of-1 trial: a pilot study.","volume":"5","author":"D Taragin","year":"2013","journal-title":"Atten Defic Hyperact Disord"},{"issue":"2","key":"pone.0269387.ref018","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1001\/jamacardio.2021.5010","article-title":"Individualized Studies of Triggers of Paroxysmal Atrial Fibrillation: The I-STOP-AFib Randomized Clinical Trial","volume":"7","author":"GM Marcus","year":"2022","journal-title":"JAMA Cardiol"},{"key":"pone.0269387.ref019","volume-title":"Can within-patient controlled trials help to personalize the treatment of chronic pain?:","author":"T. Buclin","year":"2018"},{"key":"pone.0269387.ref020","volume-title":"Randomized Trial Comparing N of 1 Trials to Standard Practice to Improve Adherence to Statins in Patients With Diabetes.","author":"CG McDonald","year":"2008"},{"issue":"2","key":"pone.0269387.ref021","doi-asserted-by":"crossref","first-page":"e033070","DOI":"10.1136\/bmjopen-2019-033070","article-title":"Tackling statin intolerance with n-of-1 trials (TaSINI) in primary care: protocol for a feasibility randomised trial to increase statin adherence.","volume":"10","author":"K Tudor","year":"2020","journal-title":"BMJ Open"},{"key":"pone.0269387.ref022","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41746-020-0224-8","article-title":"Indicators of retention in remote digital health studies: a cross-study evaluation of 100,000 participants.","volume":"3","author":"A Pratap","year":"2020","journal-title":"NPJ Digit Med"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0269387","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T17:39:23Z","timestamp":1654191563000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0269387"}},"subtitle":[],"editor":[{"given":"Richard","family":"Evans","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,6,2]]},"references-count":22,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0269387","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,2]]}}}