{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:53:25Z","timestamp":1787313205326,"version":"build-2736575974"},"reference-count":15,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2025,7,6]],"date-time":"2025-07-06T00:00:00Z","timestamp":1751760000000},"content-version":"unspecified","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017618","name":"Division of Diabetes, Endocrinology, and Metabolic Diseases","doi-asserted-by":"publisher","award":["U24DK122927"],"award-info":[{"award-number":["U24DK122927"]}],"id":[{"id":"10.13039\/100017618","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,6,17]]},"published-print":{"date-parts":[[2025,7]]},"abstract":"\n Objectives<\/jats:title>\n Diabetes mellitus (DM) affects over 422\u2009million individuals globally. Diabetic foot ulcers (DFUs) stand out as a challenging complication of DM, affecting up to 34% of individuals with DM. Despite the prevalence of DFUs, clinical trials for DFUs often face slow and insufficient patient recruitment. We aimed to identify key determinants that impact subject recruitment rates in DFU clinical trials.<\/jats:p>\n <\/jats:sec>\n \n Design<\/jats:title>\n Systematic review.<\/jats:p>\n <\/jats:sec>\n \n Data sources<\/jats:title>\n ClinicalTrials.gov and PubMed were searched to identify DFU clinical studies published from 1 January 1990 to 9 April 2025.<\/jats:p>\n <\/jats:sec>\n \n Eligibility criteria<\/jats:title>\n We included English-language publications of clinical trials aimed at healing DFUs that reported enrolment numbers, duration of enrolment and number of study centres.<\/jats:p>\n <\/jats:sec>\n \n Data extraction and synthesis<\/jats:title>\n Records were extracted and subjected to two independent rounds of review by five authors (LZ, SP, RN, HL-T, and RK). Data were pooled and analysed using negative binomial regression, Kaplan-Meier methods and Cox proportional hazards models. Study enrolment and site enrolment rates, as well as time to complete study enrolment, were analysed. Between-study heterogeneity was assessed using the likelihood ratio test.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n 397 trials involving 31\u2009955 participants were included. On average, DFU studies enrolled 4.24 patients per month (median: 1.65). US-based studies had slower recruitment than non-US studies, with a mean enrolment rate of 1.51 patients per site per month (median: 0.58). The average time to complete enrolment was 1.28 years. Studies that employed a higher number of study sites, were conducted outside the USA, studied behavioural or dietary supplement interventions, and began enrolment more recently, were more likely to have a higher enrolment rate. Longer time to complete enrolment was associated with a larger number of study sites, trials involving at least one US site, earlier starting enrolment year, and longer follow-up duration.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n These findings have potential practical implications for the design and conduct of future DFU trials.<\/jats:p>\n <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-095512","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T01:25:39Z","timestamp":1751851539000},"page":"e095512","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Determinants of enrolment rate in 397 clinical trials for healing diabetic foot ulcers: a systematic review"],"prefix":"10.1136","volume":"15","author":[{"given":"Leyao","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3619-2804","authenticated-orcid":false,"given":"Soumik","family":"Purkayastha","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Health Data Science, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"},{"name":"Center for Health Equity Research and Promotion, VA Pittsburgh Health System, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadar","family":"Lev-Tov","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Cutaneous Surgery, University of Miami, Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Nie","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Kirsner","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Cutaneous Surgery, University of Miami, Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathie","family":"Spino","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7881-7182","authenticated-orcid":false,"given":"Peter X K","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,7,6]]},"reference":[{"key":"2025121510160769000_15.7.e095512.1","unstructured":"World Health Organization . Diabetes. 2023. Available: https:\/\/www.who.int\/news-room\/detail\/22-09-2020-tobacco-responsible-for-20-of-deaths-from-coronary-heart-disease"},{"key":"2025121510160769000_15.7.e095512.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1615439"},{"key":"2025121510160769000_15.7.e095512.3","doi-asserted-by":"publisher","DOI":"10.1111\/iwj.12404"},{"key":"2025121510160769000_15.7.e095512.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2012.09.014"},{"key":"2025121510160769000_15.7.e095512.5","unstructured":"O. of Therapeutics Research, C. f. B. E. Review, and F. Research . Product approval information - licensing action."},{"key":"2025121510160769000_15.7.e095512.6","first-page":"91665","article-title":"Survival Analysis","volume":"510","author":"Kleinbaum","year":"2005","journal-title":"Statis Biol Health Survival"},{"key":"2025121510160769000_15.7.e095512.7","doi-asserted-by":"publisher","DOI":"10.2307\/1268249"},{"key":"2025121510160769000_15.7.e095512.8","article-title":"Survival Analysis","volume":"10","author":"Klein","year":"2003","journal-title":"Statis Biol Health"},{"key":"2025121510160769000_15.7.e095512.9","article-title":"Clinical trials: what gets registered and why","volume":"12","author":"Ehrhardt","year":"2015","journal-title":"PLoS Med"},{"key":"2025121510160769000_15.7.e095512.10","doi-asserted-by":"crossref","first-page":"209","DOI":"10.2337\/dci22-0043","article-title":"Etiology, Epidemiology, and Disparities in the Burden of Diabetic Foot Ulcers","volume":"46","author":"McDermott","year":"2023","journal-title":"Diabetes Care"},{"key":"2025121510160769000_15.7.e095512.11","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1007\/s12178-023-09867-7","article-title":"Racial and Ethnic Disparities in the Management of Diabetic Feet","volume":"16","author":"Clayton","year":"2023","journal-title":"Curr Rev Musculoskelet Med"},{"key":"2025121510160769000_15.7.e095512.12","doi-asserted-by":"crossref","DOI":"10.2196\/52036","article-title":"Empowering Foot Care Literacy Among People Living With Diabetes and Their Carers With an mHealth App: Protocol for a Feasibility Study","volume":"12","author":"Liew","year":"2023","journal-title":"JMIR Res Protoc"},{"key":"2025121510160769000_15.7.e095512.13","doi-asserted-by":"crossref","DOI":"10.1126\/science.adq4994","article-title":"The value of decentralized clinical trials: Inclusion, accessibility, and innovation","volume":"385","author":"Jean-Louis","year":"2024","journal-title":"Science"},{"key":"2025121510160769000_15.7.e095512.14","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.2337\/dc25-0300","article-title":"High Transepidermal Water Loss at the Site of Wound Closure Is Associated With Increased Recurrence of Diabetic Foot Ulcers: The NIDDK Diabetic Foot Consortium TEWL Study","volume":"48","author":"Sen","year":"2025","journal-title":"Diabetes Care"},{"key":"2025121510160769000_15.7.e095512.15","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.jaad.2022.05.020","article-title":"Modified Score of Toxic Epidermal Necrolysis to predict toxic epidermal necrolysis mortality","volume":"88","author":"Haghani Dogahe","year":"2023","journal-title":"J Am Acad Dermatol"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2024-095512","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T18:16:13Z","timestamp":1765822573000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2024-095512"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":15,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7,6]]},"published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1136\/bmjopen-2024-095512"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2024-095512","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7]]}}}