{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,4]],"date-time":"2025-05-04T04:03:09Z","timestamp":1746331389041,"version":"3.40.4"},"reference-count":11,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,3]],"date-time":"2025-05-03T00:00:00Z","timestamp":1746230400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,3]],"date-time":"2025-05-03T00:00:00Z","timestamp":1746230400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med Res Methodol"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>REFRACT is a randomised trial aimed at rapidly evaluating multiple novel therapies against standard treatment for relapsed or refractory follicular lymphoma (rrFL) using a minimal number of patients. To this end, we designed a prospective, adaptive, sequentially randomised clinical trial to allow multiple novel therapies to be assessed sequentially against a control arm of investigator choice standard therapy (ICT).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>REFRACT uses a Bayesian power priors approach enabling the sharing of control arm data from previous treatment rounds. The design allows for the randomisation ratio to be changed and fixed to 1:4 in later treatment rounds resulting in fewer patients being recruited to the control arm.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Following extensive simulations, we arrived at the selected design of three sequential treatment rounds, each with a control group and a novel experimental arm assessed for the primary outcome of complete metabolic response\u00a0(CMR) at 24 weeks. Patients in Round 1 are randomised using a 1:1 allocation, with Rounds 2 and 3 randomised using a 1:4 allocation, in favour of experimental treatment. Using Bayesian power priors, data from control patients in earlier rounds will be shared to improve the operating characteristics in the current round. Previous control arm patients will be weighted at 75% of an active control patient within the prior, with opportunities for adjustment should control treatments change over time.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>With the use of power priors and an adaptive design this trial will sequentially evaluate three novel treatment regimens in a disease that urgently requires additional treatment options. REFRACT opened to recruitment in July 2023.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Trial registration<\/jats:title>\n            <jats:p>EudraCT: 2022\u2013000677-75; 10-Feb-2022.<\/jats:p>\n            <jats:p>ClinicalTrials.gov: NCT05848765; 08-May-2023.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12874-025-02575-5","type":"journal-article","created":{"date-parts":[[2025,5,3]],"date-time":"2025-05-03T08:29:41Z","timestamp":1746260981000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The REFRACT trial: implementation of Bayesian power priors in a randomised, sequential phase II adaptive platform trial"],"prefix":"10.1186","volume":"25","author":[{"given":"Charlotte","family":"Gaskell","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kim","family":"Linton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Bishton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graham","family":"McIlroy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Si\u00e2n","family":"Lax","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Fox","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise","family":"Hopkins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Collings","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malcolm","family":"Rhodes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tania","family":"Seale","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aimee","family":"Jackson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,5,3]]},"reference":[{"key":"2575_CR1","unstructured":"Singh D, Singh A, Mukkamalla SKR. Relapsed and refractory follicular lymphoma [Updated 2023 Jan 15]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available at: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK589677\/. Accessed 20 Sep 2024."},{"issue":"1","key":"2575_CR2","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1182\/asheducation-2016.1.269","volume":"2016","author":"C Casulo","year":"2016","unstructured":"Casulo C. Prognostic factors in follicular lymphoma: new tools to personalize risk. Hematology Am Soc Hematol Educ Program. 2016;2016(1):269\u201376. https:\/\/doi.org\/10.1182\/asheducation-2016.1.269.","journal-title":"Hematology Am Soc Hematol Educ Program"},{"key":"2575_CR3","unstructured":"ClinicalTrials.gov. Active phase 2 and 3 trials in follicular lymphoma 2020. Available at: https:\/\/clinicaltrials.gov\/ct2\/results?cond=relapsed+follicular+lymphoma&recrs=b&recrs=a&recrs=f&recrs=d&age_v=&gndr=&type=Intr&rslt=&phase=1&phase=2&Search=Apply. 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Introduction to Bayesian Statistics. 3rd ed: John Wiley & Sons; 2016.","DOI":"10.1002\/9781118593165"},{"issue":"2","key":"2575_CR7","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1038\/s41416-021-01613-5","volume":"126","author":"H Mossop","year":"2022","unstructured":"Mossop H, Grayling MJ, Gallagher FA, Welsh SJ, Stewart GD, Wason JMS. Advantages of multi-arm non-randomised sequentially allocated cohort designs for Phase II oncology trials. Br J Cancer. 2022;126(2):204\u201310. https:\/\/doi.org\/10.1038\/s41416-021-01613-5. Epub 2021 Nov 8. PMID: 34750494; PMCID: PMC8770479.","journal-title":"Br J Cancer."},{"issue":"28","key":"2575_CR8","doi-asserted-by":"publisher","first-page":"3724","DOI":"10.1002\/sim.6728","volume":"34","author":"JG Ibrahim","year":"2015","unstructured":"Ibrahim JG, Chen MH, Gwon Y, et al. The power prior: theory and applications. Stat Med. 2015;34(28):3724\u201349. https:\/\/doi.org\/10.1002\/sim.6728.","journal-title":"Stat Med"},{"issue":"1","key":"2575_CR9","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1186\/s12885-024-12112-0","volume":"24","author":"G McIlroy","year":"2024","unstructured":"McIlroy G, Lax S, Gaskell C, et al. Investigator choice of standard therapy versus sequential novel therapy arms in the treatment of relapsed follicular lymphoma (REFRACT): study protocol for a multi-centre, open-label, randomised, phase II platform trial. BMC Cancer. 2024;24(1):370. https:\/\/doi.org\/10.1186\/s12885-024-12112-0.","journal-title":"BMC Cancer"},{"issue":"27","key":"2575_CR10","doi-asserted-by":"publisher","first-page":"3059","DOI":"10.1200\/JCO.2013.54.8800","volume":"32","author":"BD Cheson","year":"2014","unstructured":"Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32(27):3059\u201368. https:\/\/doi.org\/10.1200\/JCO.2013.54.8800.","journal-title":"J Clin Oncol"},{"issue":"2","key":"2575_CR11","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1002\/pst.2349","volume":"23","author":"F Mariani","year":"2024","unstructured":"Mariani F, De Santis F, Gubbiotti S. A dynamic power prior approach to non-inferiority trials for normal means. Pharm Stat. 2024;23(2):242\u201356. https:\/\/doi.org\/10.1002\/pst.2349.","journal-title":"Pharm Stat"}],"container-title":["BMC Medical Research Methodology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12874-025-02575-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12874-025-02575-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12874-025-02575-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,3]],"date-time":"2025-05-03T08:29:43Z","timestamp":1746260983000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcmedresmethodol.biomedcentral.com\/articles\/10.1186\/s12874-025-02575-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,3]]},"references-count":11,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["2575"],"URL":"https:\/\/doi.org\/10.1186\/s12874-025-02575-5","relation":{},"ISSN":["1471-2288"],"issn-type":[{"value":"1471-2288","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,3]]},"assertion":[{"value":"20 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 April 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 May 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The REFRACT protocol has been approved by the UK (London\u2014Fulham Research Ethics Committee on 22-Jun-2023); current version 2.0, 03-May-2023. Competent Authority approval was granted in the UK by the Medicines and Healthcare Products Regulatory Agency (MHRA) on 01-Jun-2023.All patients provide written informed consent to participate.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"MB: Honoraria from Abbvie, Roche, Celltrion and Gilead.  Consulting or advisory role for Incyte, Roche, Lilly and Abbvie, Research funding from Roche and Takeda. Travel expenses from Roche.  All other authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"121"}}