{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T15:53:48Z","timestamp":1782489228574,"version":"3.54.5"},"reference-count":31,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"unspecified","delay-in-days":10,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015570","name":"Blood Cancer UK","doi-asserted-by":"publisher","award":["Transformational Research Award 25004"],"award-info":[{"award-number":["Transformational Research Award 25004"]}],"id":[{"id":"10.13039\/501100015570","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["Leeds CRUK Clinical Trials Unit CTUQQR- Dec22\/1000"],"award-info":[{"award-number":["Leeds CRUK Clinical Trials Unit CTUQQR- Dec22\/1000"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018955","name":"Leeds Biomedical Research Centre","doi-asserted-by":"publisher","award":["NIHR203331"],"award-info":[{"award-number":["NIHR203331"]}],"id":[{"id":"10.13039\/501100018955","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,4,22]]},"published-print":{"date-parts":[[2026,5]]},"abstract":"\n Introduction<\/jats:title>\n Randomised clinical trials (RCTs) are gold standard in evidence-based medicine, but follow-up typically relies on clinic visits and trial-specific data collection. Much of this information overlaps with routinely collected healthcare systems data (HSD), such as electronic health records and national registries. Leveraging HSD for trial follow-up has the potential to reduce cost, time and resource burden. However, concerns remain about data quality and evidence is needed to show that HSD-based outcomes are reported to an equivalent standard to trial-specific data.<\/jats:p>\n The Blood Cancer Clinical Trials Long-term Follow-up Using Integrated Healthcare Systems platform will link data collected from multiple myeloma clinical trials with HSD to create a research database supporting extended follow-up and further methodological and clinical research.<\/jats:p>\n <\/jats:sec>\n \n Methods and analysis<\/jats:title>\n This data-linkage study includes participants from multiple myeloma RCTs conducted by the University of Leeds between 2008 and 2021. NHS (National Health Service) England will link these participants to HSD, including deaths and cancer registrations, systemic anticancer therapy, radiotherapy and Hospital Episode Statistics.<\/jats:p>\n We will compare trial-collected outcomes with those derived from HSD, including mortality, treatment, second cancer incidence and major adverse events. Long-term overall survival will be estimated using national mortality data. HSD-derived demographic and clinical variables will be used to assess population representativeness relative to the wider myeloma population. Time to next treatment will be derived and evaluated as a surrogate for progression-free survival. HSD-derived frailty measures will be examined for prognostic utility, and radiotherapy and hospital records will be analysed to characterise bone-related treatments and skeletal complications.<\/jats:p>\n <\/jats:sec>\n \n Ethics and dissemination<\/jats:title>\n Ethical approval has been obtained from the East of England\u2013Cambridge Central Research Ethics Committee, with Section\u202f251 support from the Health Research Authority on advice from the Confidentiality Advisory Group. Findings will be disseminated through publications, conference presentations and engagement with stakeholders and patient groups.<\/jats:p>\n <\/jats:sec>\n \n Trial registration<\/jats:title>\n \n ISRCTN60123120<\/jats:ext-link>\n ,\n ISRCTN49407852<\/jats:ext-link>\n ,\n ISRCTN90889843<\/jats:ext-link>\n ,\n ISRCTN24989786<\/jats:ext-link>\n ,\n ISRCTN08577602<\/jats:ext-link>\n ,\n ISRCTN17354232<\/jats:ext-link>\n ,\n ISRCTN59395590<\/jats:ext-link>\n ,\n ISRCTN24593488<\/jats:ext-link>\n ,\n ISRCTN58227268<\/jats:ext-link>\n ,\n ISRCTN15028850<\/jats:ext-link>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1136\/bmjopen-2026-120416","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T12:35:52Z","timestamp":1778502952000},"page":"e120416","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Blood Cancer Clinical Trials Long-term Follow-up Using Integrated Healthcare Systems Data (BLISS): protocol for a data-linkage study integrating randomised clinical trials with national healthcare systems data"],"prefix":"10.1136","volume":"16","clinical-trial-number":[{"clinical-trial-number":"isrctn60123120","registry":"10.18810\/isrctn","type":"postResults"},{"clinical-trial-number":"isrctn49407852","registry":"10.18810\/isrctn","type":"postResults"},{"clinical-trial-number":"isrctn90889843","registry":"10.18810\/isrctn","type":"postResults"},{"clinical-trial-number":"isrctn24989786","registry":"10.18810\/isrctn","type":"postResults"},{"clinical-trial-number":"isrctn08577602","registry":"10.18810\/isrctn","type":"postResults"},{"clinical-trial-number":"isrctn17354232","registry":"10.18810\/isrctn","type":"postResults"},{"clinical-trial-number":"isrctn59395590","registry":"10.18810\/isrctn","type":"postResults"},{"clinical-trial-number":"isrctn24593488","registry":"10.18810\/isrctn","type":"postResults"},{"clinical-trial-number":"isrctn58227268","registry":"10.18810\/isrctn","type":"postResults"},{"clinical-trial-number":"isrctn15028850","registry":"10.18810\/isrctn","type":"postResults"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4280-6323","authenticated-orcid":false,"given":"Lesley","family":"Smith","sequence":"first","affiliation":[{"name":"Leeds Cancer Research UK Clinical Trials Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4821-5115","authenticated-orcid":false,"given":"Janice","family":"Hoang","sequence":"additional","affiliation":[{"name":"Leeds Cancer Research UK Clinical Trials Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Gillson","sequence":"additional","affiliation":[{"name":"Leeds Cancer Research UK Clinical Trials Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanine","family":"Richards","sequence":"additional","affiliation":[{"name":"Leeds Cancer Research UK Clinical Trials Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon","family":"Cook","sequence":"additional","affiliation":[{"name":"Leeds Cancer Research UK Clinical Trials Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK"},{"name":"NIHR Leeds Biomedical Research Centre, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7975-7537","authenticated-orcid":false,"given":"Sarah","family":"Brown","sequence":"additional","affiliation":[{"name":"Leeds Cancer Research UK Clinical Trials Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0225-1199","authenticated-orcid":false,"given":"Kara-Louise","family":"Royle","sequence":"additional","affiliation":[{"name":"Leeds Cancer Research UK Clinical Trials Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadie","family":"Roberts","sequence":"additional","affiliation":[{"name":"Leeds Cancer Research UK Clinical Trials Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Olivier","sequence":"additional","affiliation":[{"name":"Leeds Cancer Research UK Clinical Trials Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Parish","sequence":"additional","affiliation":[{"name":"Leeds Cancer Research UK Clinical Trials Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Spencer","sequence":"additional","affiliation":[{"name":"Academic Unit of Health Economics, Leeds Institute of Health Sciences, University of Leeds, Leeds, UK"},{"name":"National Disease Registration Service, NHS England, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelagh","family":"Thompson","sequence":"additional","affiliation":[{"name":"Patient Representative, Basingstoke, Hampshire, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Cairns","sequence":"additional","affiliation":[{"name":"Leeds Cancer Research UK Clinical Trials Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"key":"2026062608320319000_16.5.e120416.1","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2020-043906","article-title":"Realising the full potential of data-enabled trials in the UK: a call for action","volume":"11","author":"Sydes","year":"2021","journal-title":"BMJ Open"},{"key":"2026062608320319000_16.5.e120416.2","unstructured":"Health Data Research UK . Transforming Data for Trials, 2024. Available: https:\/\/www.hdruk.ac.uk\/research\/research-data-infrastructure\/transforming-data-for-trials\/ [Accessed 26 Mar 2026]."},{"key":"2026062608320319000_16.5.e120416.3","unstructured":"O\u2019Shaughnessy J . Commercial clinical trials in the UK: the Lord O\u2019Shaughnessy review-final report. 2023."},{"key":"2026062608320319000_16.5.e120416.4","doi-asserted-by":"crossref","first-page":"107514","DOI":"10.1016\/j.cct.2024.107514","article-title":"Getting our ducks in a row: The need for data utility comparisons of healthcare systems data for clinical trials","volume":"141","author":"Sydes","year":"2024","journal-title":"Contemp Clin Trials"},{"key":"2026062608320319000_16.5.e120416.5","doi-asserted-by":"crossref","DOI":"10.1186\/s13063-024-07926-z","article-title":"Using healthcare systems data for outcomes in clinical trials: issues to consider at the design stage","volume":"25","author":"Toader","year":"2024","journal-title":"Trials"},{"key":"2026062608320319000_16.5.e120416.6","doi-asserted-by":"crossref","first-page":"e567","DOI":"10.1016\/S2589-7500(22)00122-4","article-title":"Data provenance and integrity of health-care systems data for clinical trials","volume":"4","author":"Murray","year":"2022","journal-title":"Lancet Digit Health"},{"key":"2026062608320319000_16.5.e120416.7","unstructured":"Murray ML , Pinches H , Mafham M , et al . Use of NHS Digital datasets as trial data in the UK: a position paper. 2022. Available: https:\/\/zenodo.org\/records\/6047155"},{"key":"2026062608320319000_16.5.e120416.8","doi-asserted-by":"crossref","DOI":"10.1186\/s13063-017-2308-6","article-title":"Can routine data be used to support cancer clinical trials? A historical baseline on which to build: retrospective linkage of data from the TACT (CRUK 01\/001) breast cancer trial and the National Cancer Data Repository","volume":"18","author":"Kilburn","year":"2017","journal-title":"Trials"},{"key":"2026062608320319000_16.5.e120416.9","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.canep.2018.11.011","article-title":"Colorectal cancer ascertainment through cancer registries, hospital episode statistics, and self-reporting compared to confirmation by clinician: A cohort study nested within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)","volume":"58","author":"Thomas","year":"2019","journal-title":"Cancer Epidemiol"},{"key":"2026062608320319000_16.5.e120416.10","doi-asserted-by":"crossref","DOI":"10.1186\/s13063-020-04968-x","article-title":"Completeness and accuracy of national cancer and death registration for outcome ascertainment in trials-an ovarian cancer exemplar","volume":"22","author":"Kalsi","year":"2021","journal-title":"Trials"},{"key":"2026062608320319000_16.5.e120416.11","doi-asserted-by":"crossref","DOI":"10.1186\/s13063-021-05613-x","article-title":"Use of routinely collected health data in randomised clinical trials: comparison of trial-specific death data in the BOSS trial with NHS Digital data","volume":"22","author":"Love","year":"2021","journal-title":"Trials"},{"key":"2026062608320319000_16.5.e120416.12","unstructured":"NHS England . Civil registration of deaths dataset. 2025. Available: https:\/\/digital.nhs.uk\/services\/data-services-for-commissioners\/datasets\/civil-registration-of-deaths-dataset [Accessed 27 Mar 2026]."},{"key":"2026062608320319000_16.5.e120416.13","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyz076"},{"key":"2026062608320319000_16.5.e120416.14","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyz137"},{"key":"2026062608320319000_16.5.e120416.15","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2022-070699","article-title":"Cohort profile: radiotherapy dataset (RTDS) in England","volume":"13","author":"Sandhu","year":"2023","journal-title":"BMJ Open"},{"key":"2026062608320319000_16.5.e120416.16","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyx015"},{"key":"2026062608320319000_16.5.e120416.17","unstructured":"World Health Organization . ICD-10: international statistical classification of diseases and related health problems (10th revision). 2019. Available: https:\/\/icd.who.int\/browse10\/2019\/en [Accessed 26 Mar 2026]."},{"key":"2026062608320319000_16.5.e120416.18","unstructured":"NHS England . NHS classifications browser: OPCS\u20114 \u2013 classification of interventions and procedures. Available: https:\/\/classbrowser.nhs.uk\/ [Accessed 26 Mar 2026]."},{"key":"2026062608320319000_16.5.e120416.19","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.canep.2013.08.014","article-title":"Estimating the proportion cured of cancer: some practical advice for users","volume":"37","author":"Yu","year":"2013","journal-title":"Cancer Epidemiol"},{"key":"2026062608320319000_16.5.e120416.20","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/1.1.49"},{"key":"2026062608320319000_16.5.e120416.21","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4780080407"},{"key":"2026062608320319000_16.5.e120416.22","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1016\/S1470-2045(22)00506-X","article-title":"Recurrence-free survival versus overall survival as a primary endpoint for studies of resected colorectal liver metastasis: a retrospective study and meta-analysis","volume":"23","author":"Ecker","year":"2022","journal-title":"Lancet Oncol"},{"key":"2026062608320319000_16.5.e120416.23","doi-asserted-by":"crossref","first-page":"2634","DOI":"10.1177\/09622802211046390","article-title":"Conditional copula models for correlated survival endpoints: Individual patient data meta-analysis of randomized controlled trials","volume":"30","author":"Emura","year":"2021","journal-title":"Stat Methods Med Res"},{"key":"2026062608320319000_16.5.e120416.24","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1002\/bimj.201900306","article-title":"A joint frailty-copula model for meta-analytic validation of failure time surrogate endpoints in clinical trials","volume":"63","author":"Sofeu","year":"2021","journal-title":"Biom J"},{"key":"2026062608320319000_16.5.e120416.25","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/s41375-019-0539-0","article-title":"A simplified frailty scale predicts outcomes in transplant-ineligible patients with newly diagnosed multiple myeloma treated in the FIRST (MM-020) trial","volume":"34","author":"Facon","year":"2020","journal-title":"Leukemia"},{"key":"2026062608320319000_16.5.e120416.26","doi-asserted-by":"crossref","first-page":"e154","DOI":"10.1016\/S2352-3026(18)30220-5","article-title":"A clinical prediction model for outcome and therapy delivery in transplant-ineligible patients with myeloma (UK Myeloma Research Alliance Risk Profile): a development and validation study","volume":"6","author":"Cook","year":"2019","journal-title":"Lancet Haematol"},{"key":"2026062608320319000_16.5.e120416.27","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2015-008457","article-title":"Developing and validating a risk prediction model for acute care based on frailty syndromes","volume":"5","author":"Soong","year":"2015","journal-title":"BMJ Open"},{"key":"2026062608320319000_16.5.e120416.28","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(18)30668-8"},{"key":"2026062608320319000_16.5.e120416.29","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2019-035395","article-title":"Construction of the secondary care administrative records frailty (SCARF) index and validation on older women with operable invasive breast cancer in England and Wales: a cohort study","volume":"10","author":"Jauhari","year":"2020","journal-title":"BMJ Open"},{"key":"2026062608320319000_16.5.e120416.30","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2288-13-33","article-title":"External validation of a Cox prognostic model: principles and methods","volume":"13","author":"Royston","year":"2013","journal-title":"BMC Med Res Methodol"},{"key":"2026062608320319000_16.5.e120416.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.canep.2019.101628"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2026-120416","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T15:43:49Z","timestamp":1782488629000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2026-120416"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":31,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5,11]]},"published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1136\/bmjopen-2026-120416"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2026-120416","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5]]}}}