{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T12:15:06Z","timestamp":1775996106221,"version":"3.50.1"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","funder":[{"DOI":"10.13039\/501100000659","name":"Research Trainees Coordinating Centre","doi-asserted-by":"publisher","award":["DRF-2016-09-065"],"award-info":[{"award-number":["DRF-2016-09-065"]}],"id":[{"id":"10.13039\/501100000659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"published-print":{"date-parts":[[2018,12]]},"DOI":"10.1186\/s13063-017-2432-3","type":"journal-article","created":{"date-parts":[[2018,1,8]],"date-time":"2018-01-08T07:35:57Z","timestamp":1515396957000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Commentary: considerations for using the \u2018Trials within Cohorts\u2019 design in a clinical trial of an investigational medicinal product"],"prefix":"10.1186","volume":"19","author":[{"given":"Anna C.","family":"Bibby","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Torgerson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha","family":"Leach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Lewis-White","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nick A.","family":"Maskell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,1,8]]},"reference":[{"key":"2432_CR1","doi-asserted-by":"crossref","first-page":"c1066","DOI":"10.1136\/bmj.c1066","volume":"340","author":"C Relton","year":"2010","unstructured":"Relton C, Torgerson D, O\u2019Cathain A, Nicholl J. Rethinking pragmatic randomised controlled trials: introducing the \u201ccohort multiple randomised controlled trial\u201d design. Br Med J. 2010;340:c1066.","journal-title":"Br Med J"},{"key":"2432_CR2","first-page":"96","volume":"46","author":"JM Velden van der","year":"2017","unstructured":"van der Velden JM, Verkooijen HM, Young-Afat DA, Burbach JPM, van Vulpen M, Relton C, et al. The cohort multiple randomized controlled trial design: a valid and efficient alternative to pragmatic trials? Int J Epidemiol. 2017;46:96\u2013102.","journal-title":"Int J Epidemiol"},{"issue":"17","key":"2432_CR3","first-page":"A5762","volume":"157","author":"H Verkooijen","year":"2013","unstructured":"Verkooijen H, Roes K, van Gils C. Cohort multiple randomized controlled trial: a solution for the evaluation of multiple interventions. Ned Tijdschr Geneeskd. 2013;157(17):A5762.","journal-title":"Ned Tijdschr Geneeskd"},{"key":"2432_CR4","doi-asserted-by":"crossref","first-page":"h2147","DOI":"10.1136\/bmj.h2147","volume":"350","author":"K Loudon","year":"2015","unstructured":"Loudon K, Treweek S, Sullivan F, Donnan P, Thorpe KE, Zwarenstein M. The PRECIS-2 tool: designing trials that are fit for purpose. Br Med J. 2015;350:h2147.","journal-title":"Br Med J"},{"issue":"4","key":"2432_CR5","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1056\/NEJMp1005843","volume":"363","author":"RC Young","year":"2010","unstructured":"Young RC. Cancer clinical trials--a chronic but curable crisis. N Engl J Med. 2010;363(4):306\u20139.","journal-title":"N Engl J Med"},{"issue":"3","key":"2432_CR6","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1097\/EDE.0000000000000435","volume":"27","author":"DA Young-Afat","year":"2016","unstructured":"Young-Afat DA, Verkooijen HAM, van Gils CH, van der Velden JM, Burbach JP, Elias SG, et al. Brief report: staged-informed consent in the cohort multiple randomized controlled trial design. Epidemiology. 2016;27(3):389\u201392.","journal-title":"Epidemiology"},{"key":"2432_CR7","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1186\/1745-6215-15-398","volume":"15","author":"DA Richards","year":"2014","unstructured":"Richards DA, Ross S, Robens S, Borglin G. The DiReCT study - improving recruitment into clinical trials: a mixed methods study investigating the ethical acceptability, feasibility and recruitment yield of the cohort multiple randomised controlled trials design. Trials. 2014;15:398.","journal-title":"Trials"},{"issue":"Suppl 2","key":"2432_CR8","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1186\/s13063-017-1961-0","volume":"18","author":"C Relton","year":"2017","unstructured":"Relton C, Burbach M, Collett C, Flory J, Gerlich S, Holm S, et al. The ethics of \u2018Trials within Cohorts\u2019 (TwiCs): 2nd international symposium: London, UK. 7\u20138 November 2016. Trials. 2017;18 Suppl 2:244.","journal-title":"Trials"},{"key":"2432_CR9","unstructured":"Health Research Authority. HRA Guidance on applying a proportionate approach to the process of seeking consent. file:\/\/\/C:\/Users\/ab9709\/Chrome%20Local%20Downloads\/applying-proportionate-approach-process-seeking-consent_R3gbJKn.pdf. Accessed 30 Nov 2017."},{"issue":"1","key":"2432_CR10","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1186\/1471-2458-11-640","volume":"11","author":"C Relton","year":"2011","unstructured":"Relton C, Bissell P, Smith C, Blackburn J, Cooper CL, Nicholl J, et al. South Yorkshire Cohort: a \u2018cohort trials facility\u2019 study of health and weight - Protocol for the recruitment phase. BMC Public Health. 2011;11(1):640.","journal-title":"BMC Public Health"},{"issue":"1","key":"2432_CR11","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s13063-015-0586-4","volume":"16","author":"JM Burbach","year":"2015","unstructured":"Burbach JM, Verkooijen HM, Intven M, Kleijnen J-PJ, Bosman ME, Raaymakers BW, et al. RandomizEd controlled trial for pre-operAtive dose-escaLation BOOST in locally advanced rectal cancer (RECTAL BOOST study): study protocol for a randomized controlled trial. Trials. 2015;16(1):58.","journal-title":"Trials"},{"issue":"1","key":"2432_CR12","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1186\/s13063-016-1256-x","volume":"17","author":"AM Couwenberg","year":"2016","unstructured":"Couwenberg AM, Burbach MJ, Smits AB, Van Vulpen M, Van Grevenstein WM, Noordzij PG, et al. The impact of retractor SPONGE-assisted laparoscopic surgery on duration of hospital stay and postoperative complications in patients with colorectal cancer (SPONGE trial): study protocol for a randomized controlled trial. Trials. 2016;17(1):132.","journal-title":"Trials"},{"issue":"2","key":"2432_CR13","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.homp.2014.01.004","volume":"103","author":"P Viksveen","year":"2014","unstructured":"Viksveen P, Relton C. Depression treated by homeopaths: a study protocol for a pragmatic cohort multiple randomised controlled trial. Homeopathy. 2014;103(2):147\u201352.","journal-title":"Homeopathy"},{"issue":"8","key":"2432_CR14","doi-asserted-by":"crossref","first-page":"e003563","DOI":"10.1136\/bmjopen-2013-003563","volume":"3","author":"L Kwakkenbos","year":"2013","unstructured":"Kwakkenbos L, Jewett LR, Baron M, Bartlett SJ, Furst D, Gottesman K, et al. The Scleroderma Patient-centered Intervention Network (SPIN) Cohort: protocol for a cohort multiple randomised controlled trial (cmRCT) design to support trials of psychosocial and rehabilitation interventions in a rare disease context. BMJ Open. 2013;3(8):e003563.","journal-title":"BMJ Open"},{"key":"2432_CR15","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1186\/s12885-016-2947-0","volume":"16","author":"JM Velden van der","year":"2016","unstructured":"van der Velden JM, Verkooijen HM, Seravalli E, Hes J, Gerlich AS, Kasperts N, et al. Comparing conVEntional RadioTherapy with stereotactIC body radiotherapy in patients with spinAL metastases: study protocol for a randomized controlled trial following the cohort multiple randomized controlled trial design. BMC Cancer. 2016;16:909.","journal-title":"BMC Cancer"},{"key":"2432_CR16","unstructured":"The European Parliament and the Council of the European Union. Regulation (EU) No 536\/2014 of the European Parliament and of the Council of 16th April 2014 on clinical trials on medicinal products for human use, and repealing Directive 2001\/20\/EC. Off J Eur Union. 2014;57(L158):1\u201376."},{"issue":"9","key":"2432_CR17","first-page":"13","volume":"91","author":"G Verheugen","year":"2005","unstructured":"Verheugen G. Commission directive 2005\/28\/ec laying down principles and guidelines for good clinical practice as regards investigational medicinal products for human use, as well as the requirements for authorization of the manufacturing or importation of such products. Off J Eur Union. 2005;91(9):13\u20139.","journal-title":"Off J Eur Union"},{"key":"2432_CR18","unstructured":"European Parliament. Directive 2001\/20\/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use. \nhttp:\/\/eur-lex.europa.eu\/legal-content\/EN\/TXT\/?uri=CELEX:02001L0020-20090807\n\n. Accessed 16 Aug 2017."},{"key":"2432_CR19","unstructured":"US Food & Drug Administration. FDA regulations relating to Good Clinical Practice and clinical trials. \nhttps:\/\/www.fda.gov\/ScienceResearch\/SpecialTopics\/RunningClinicalTrials\/ucm155713.htm\n\n. Accessed 16 July 2017."},{"key":"2432_CR20","unstructured":"UK Secretary of State. The Medicines for Human Use (Clinical Trials) Regulations 2004. \nhttp:\/\/www.legislation.gov.uk\/uksi\/2004\/1031\/contents\/made\n\n. Accessed 16 Aug 2017."},{"key":"2432_CR21","unstructured":"The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Guidelines for Good Clinical Practice (GCP) E6 (R1) 1996. \nhttps:\/\/www.ich.org\/fileadmin\/Public_Web_Site\/ICH_Products\/Guidelines\/Efficacy\/E6\/E6_R1_Guideline.pdf\n\n. Accessed 16 Aug 2017."},{"issue":"22","key":"2432_CR22","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1056\/NEJM197905313002203","volume":"300","author":"M Zelen","year":"1979","unstructured":"Zelen M. A new design for randomized clinical trials. N Engl J Med. 1979;300(22):1242\u20135.","journal-title":"N Engl J Med"},{"issue":"6","key":"2432_CR23","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1111\/j.1538-7836.2004.00782.x","volume":"2","author":"J Hawkins","year":"2004","unstructured":"Hawkins J. The ethics of Zelen consent. J Thromb Haemost. 2004;2(6):882\u20133.","journal-title":"J Thromb Haemost"},{"issue":"2","key":"2432_CR24","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1046\/j.1365-2648.2002.02164.x","volume":"38","author":"CS Homer","year":"2002","unstructured":"Homer CS. Using the Zelen design in randomized controlled trials: debates and controversies. J Adv Nurs. 2002;38(2):200\u20137.","journal-title":"J Adv Nurs"},{"issue":"12","key":"2432_CR25","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1007\/s11606-016-3780-5","volume":"31","author":"JH Flory","year":"2016","unstructured":"Flory JH, Mushlin AI, Goodman ZI. Proposals to conduct randomized controlled trials without informed consent: a narrative review. J Gen Intern Med. 2016;31(12):1511\u20138.","journal-title":"J Gen Intern Med"},{"issue":"5","key":"2432_CR26","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.jclinepi.2008.12.011","volume":"62","author":"KE Thorpe","year":"2009","unstructured":"Thorpe KE, Zwarenstein M, Oxman AD, Treweek S, Furberg CD, Altman DG, et al. A pragmatic\u2013explanatory continuum indicator summary (PRECIS): a tool to help trial designers. J Clin Epidemiol. 2009;62(5):464\u201375.","journal-title":"J Clin Epidemiol"}],"container-title":["Trials"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-017-2432-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,1,8]],"date-time":"2018-01-08T07:36:24Z","timestamp":1515396984000},"score":1,"resource":{"primary":{"URL":"https:\/\/trialsjournal.biomedcentral.com\/articles\/10.1186\/s13063-017-2432-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,8]]},"references-count":26,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,12]]}},"alternative-id":["2432"],"URL":"https:\/\/doi.org\/10.1186\/s13063-017-2432-3","relation":{},"ISSN":["1745-6215"],"issn-type":[{"value":"1745-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,8]]},"article-number":"18"}}