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

Introduction 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. 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. Methods and analysis 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. 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. Ethics and dissemination Ethical approval has been obtained from the East of England–Cambridge Central Research Ethics Committee, with Section 251 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. Trial registration ISRCTN60123120 , ISRCTN49407852 , ISRCTN90889843 , ISRCTN24989786 , ISRCTN08577602 , ISRCTN17354232 , ISRCTN59395590 , ISRCTN24593488 , ISRCTN58227268 , ISRCTN15028850 .