{"registry": "ISRCTN", "registryId": "ISRCTN13801649", "source": "https://www.isrctn.com/ISRCTN13801649", "apiSource": "https://www.isrctn.com/api/trial/ISRCTN13801649/format/default", "fetchedAt": "2026-10-07T17:01:34.265819Z", "license": "CC BY 4.0", "licenseSource": "https://www.isrctn.com/page/faqs#licence-to-post", "study": {"title": "Trial of Randomised Approaches for National Screening FOR Men (TRANSFORM)", "scientificTitle": "Trial of Randomised Approaches for National Screening FOR Men (TRANSFORM)", "acronym": "TRANSFORM", "hypothesis": "Stage 1: pilot and feasibility\nTrial design optimisation:\n1. Assess feasibility of pre- and post-randomisation consent designs in terms of screening uptake (overall and in specific sub-groups) and rates of contamination in the control groups. \n2. Investigate which recruitment approaches are most effective in terms of rate of recruitment, number of men recruited in specific sub-groups and uptake of screening.\n3. Investigate barriers and facilitators to participation in, and compliance to, screening interventions at each screening round within different socio-economic, ethnic and vulnerable groups in the community and if necessary, create strategies to improve participation and compliance.\n\nPilot prostate health checks:\n1. Evaluate biopsy rates, early-stage high, intermediate and low risk prostate cancer detection rates and model cost-effectiveness of the different intervention arms.\n2. Management of prostate cancer, testing and treatment relative adverse events and side effects.\n\nTRANSFORM Discovery:\nOperationalise TRANSFORM Discovery through optimisation and establishment of a bio-digital twin comprising a trial related tissue collection, multi-omic tissue processing, digital pathology and imaging data matched with clinical data from the main TRANSFORM database.\n\nStage 2: main trial:\nLong term cancer outcomes:\n1. Evaluate prostate cancer mortality and prostate cancer metastases.\n2. Evaluate prostate cancer incidence.\n3. Biopsy rates, early stage high, intermediate and low risk prostate cancer detection, management of prostate cancer, testing- and treatment-related adverse events and side effects.\n\nCosts and cost-effectiveness:\n1. Estimate the cost-effectiveness of strategies based on the screening intervention, compared with the current UK standard of care and update these estimates as the trial progresses.\n2. Carry out a care pathway analysis and budget impact analysis to determine resource and manpower implications of a screening recommendation within the UK healthcare system.\n\nTRANSFORM Discovery:\nTRANSFORM Discovery will deliver digital data and biospecimen collection from the trial and undertake (i) biomarker testing at scale and pace, (ii) accelerate translational & discovery science, and (iii) establish a sustainable long-term Bio-Digital Twin model.\nBiomarker testing will be undertaken, with embedded health economic evaluations, to deliver rapid real-time testing of biomarkers in collaboration with academic and commercial partners. TRANSFORM Discovery will facilitate exploratory simulations of novel strategies of healthcare delivery though data modelling to inform development of new hypotheses for prostate cancer management.", "primaryOutcome": "Stage 1: Feasibility outcomes\n1. Proportion who receive the Prostate Health Check (PHC) in each screening intervention arm (Design 1 and Design 2, separately) at the end of the trial\n2. Proportion with PSA test in each of the control groups (Design 1 and Design 2, separately) measured through linkage to national databases at the end of the trial\n\nStage 1: Prostate health checks intervention pilot outcomes\nIn each PHC group: \n1.\tProportion diagnosed with intermediate-risk prostate cancers (NCCN*) [also collected in control groups] at the end of the trial \n2.\tProportion diagnosed with low-risk prostate cancers (NCCN*) [also collected in control groups] at the end of the trial\n3.\tProportion having a prostate biopsy [also collected in control groups] at the end of the trial\n4.\tCosts and cost-effectiveness modelling of each PHC intervention (from first visit to diagnosis/treatment)", "secondaryOutcome": "Stage 1: feasibility outcomes:\n1. Proportion who provide Stage 1 consent (Design 1)\n2. Proportion with Black ethnicity invited (Designs 1 and 2 combined)\n3. Cost per successful consent (Design 1 and Design 2 separately):\n4. Proportion who provide Stage 1 consent (Design 1) by age group, ethnicity, IMD quintile\n5. Proportion of men with learning disability or severe mental illness who provide Stage 1 consent (Design 1)\n6. Proportion undergoing PHCs in each screening intervention arm by age, ethnicity, IMD quintile (Design 1)\n7. Performance indicators, including compliance with further assessment and compliance with treatment\n\nStage 1: prostate health checks intervention pilot outcomes:\nIn each randomised PHC group:\n\nTimelines:\nTime (days) from randomisation to a) undergoing the first part of each PHC to b) receiving the result of the first test to c) undergoing Prostagram™ to d) receiving the result of the Prostagram™ to e) having a prostate biopsy in those advised to undergo a prostate biopsy\n\nDetection:\n1. Proportion diagnosed with high-risk prostate cancers (NCCN*)\n2. Proportion diagnosed with low/intermediate/high-risk prostate cancer according to NICE risk groups* (* based on Cambridge Prognostic Group, low-risk = CPG1, intermediate-risk = CPG2-3, high-risk = CPG4-5, ref: ww.nice.org.uk/guidance/ng131)\n3. Proportion diagnosed by ISUP Grade Group: GG1, GG2, GG3, GG4, GG5 prostate cancer\n4. Proportion diagnosed by T stage\n5. Proportion diagnosed with any amount of Gleason 4+3=7 or more \n6. Proportion diagnosed with ≥ Gleason 4+3 OR Gleason 3+3=6 of ≥6mm (PROMIS definition 1)\n7. Proportion diagnosed with ≥ Gleason 3+4 OR Gleason 3+3=6 of ≥4mm (PROMIS definition 2) \n8. Proportion of GG2 cancers in each of the following categories of percentage pattern 4 involvement: ≤10%, 11-20%, 21-30%, 31-40%, 41-50%\n\nIn those diagnosed with prostate cancer:\n1. Maximum cancer length on biopsy in millimetres\n2. Gleason Score Ratio of GS6 to GS7+\n3. Proportion with lymph node cancer involvement of the pelvis (N1) only\n4. Proportion with distant / metastatic disease by individual stage categories: distant lymph nodes (M1a), bones (M1b) and organs such as the liver, brain or lungs (M1c) stratified by N0 or N1 status\n*NCCN Guidelines Version 4 (2024)59 will be used to define prostate cancer risk groups where indicated.\n\nBiopsy-related harms:\n1. Biopsy-related harms measured by PROBE questionnaire score\n2. Proportion with culture-proven infection related to biopsy/within 90 days of biopsy \n3. Proportion with infection treated with antibiotics (in the absence of culture confirmation) related to biopsy/within 90 days of biopsy\n4. Proportion with sepsis related to biopsy/within 90 days of biopsy\n5. Proportion with urinary retention requiring catheterisation (permanent or intermittent) related to biopsy/within 90 days of biopsy\n6. Proportion with bleeding requiring catheterisation or hospital admission related to biopsy/within 90 days of biopsy\n7. Proportion with vasovagal episode requiring hospital review or admission related to biopsy/within 90 days of biopsy\n8. Proportion whose death is related to biopsy/within 90 days of biopsy\n9. Rate of hospital admissions within 90 days after biopsy\n\nTreatment:\n1. Proportion receiving active surveillance, focal therapy, prostatectomy, and radiotherapy (with and without ADT) as first option by low, intermediate and high-risk disease subgroups (NCCN*). Proportion having ADT and type of ADT as monotherapy to be reported. \n2. Proportion receiving active surveillance, focal therapy, prostatectomy and radiotherapy (with and without ADT) as first option by low, intermediate and high-risk disease subgroups (NICE risk groups). Proportion having ADT and type of ADT as monotherapy to be reported. \n3. Proportion receiving active surveillance, focal therapy, prostatectomy and radiotherapy (with and without ADT) as first option by ISUP Grade Groups (GG1, GG2, GG3, GG4, GG5). Proportion having ADT and type of ADT as monotherapy to be reported.  \n4. Proportion receiving active surveillance, focal therapy, prostatectomy and radiotherapy (with and without ADT) as first option by T stage. Proportion having ADT and type of ADT as monotherapy to be reported. \n5. In those diagnosed with ISUP GG2 prostate cancer, proportion receiving active surveillance, focal therapy, prostatectomy and radiotherapy (with and without ADT) as first option by pattern 4 percentage categories (≤10%, 11-20%, 21-30%, 31-40%, 41-50%). Proportion having ADT and type of ADT as monotherapy to be reported. \n6. In men undergoing active surveillance, proportion who progress on biopsy or on imaging.\n7. In men undergoing active surveillance, proportion who go on to receive focal therapy, prostatectomy and radiotherapy. Proportion having ADT and type of ADT as monotherapy to be reported. \n8. In each of the following categories of stage of disease, proportions of type of local prostate treatment by focal therapy, surgery, radiotherapy and type of systemic treatment: ADT, chemotherapy, androgen receptor inhibitors (ARIs), other drugs for prostate cancer treatment and type of treatment directed at distant disease.\nNB: Breakdown of type of modality used for focal therapy to be collated. \nNB: Radiotherapy will be divided into numbers undergoing external beam radiotherapy, external beam radiotherapy with neoadjuvant ADT, external beam radiotherapy with adjuvant ADT (and duration), low dose rate brachytherapy and combination radiotherapy (high dose rate or low dose rate brachytherapy combined with external beam radiotherapy and ADT). Numbers undergoing proton therapy and stereotactic ablative radiotherapy (SABR) will also be collected. \n\nTreatment-related harms:\n1. Rate of hospital admissions within 90 days after treatment\n2. Focal therapy-related harms graded by Clavien-Dindo severity category \n3. Surgery-related harms graded by Clavien-Dindo severity category\n4. Radiotherapy-related harms graded by CTCAE severity category\n5. Other treatment-related harms graded by CTCAE severity category\n6. Investigations/ tests for treatment related symptoms, interventions for complications, death\n\nPatient reported outcome measures (PROMS):\n1. PROMS on urinary, sexual and bowel function measured by EPIC-26 Short Form\n2. Prostagram Questionnaire – all participants who received an MRI\n3. PROBE – adapted for Specification, Perceptions and General questionnaires\n4. In participants from sexual minority group, Sexual Minorities and Prostate Cancer Scale (SMACS)61\n5. Health Service Use (in draft)\n6. Health related quality of life measured by EQ-5D-5L\n7. For participants with mild or moderate learning disability, the modified version of EQ-5D-3L62 Learning Difficulty and for those with severe learning disability, the proxy (informant) version 2 of the EQ-5D-5L\n8. Demographics Questionnaire \n9. Health Behaviour and Family History Questionnaire\n10. Anxiety measured by the GAD-7 and Cancer Worry Scale (CWS) adapted to prostate cancer\n11. Health Literacy measured by the SILS \n12. Risk perception of developing prostate cancer measured on 4 items\n13. Acceptability of the received prostate health check measured (prospectively and retrospectively) on the TFA Questionnaire \n14. Participant Satisfaction Measure Questionnaire\n\nHealth economics:\n1. Proportion using health services\n2. Costs falling on men and their families\n\nTRANSFORM Discovery BDT:\n1. Define and initiate first wave biomarker validations \n2. Define consent rates to TRANSFORM Discovery and metrics of tissue (including quality assurance of biological measures), digital pathology, imaging collection and integration with clinical data.", "intervention": "\n\tIn this multi-arm multi-stage randomised platform trial, eligible men will be invited via their GP practice for a community-based screening intervention. The trial will involve two stages. In Stage 1 (pilot), two pre-consent randomisation designs will be evaluated. In Design 1, participants will be approached to express interest in joining the TRANSFORM Research Cohort. Consenting participants will be randomised to one of four screening pathways (“Prostate Health Checks”) or to a control group. Design 2 follows a “Zelen” approach, whereby participants are randomised prior to consent to one of four Prostate Health Checks or to a control. Participants in the control groups in both designs will follow usual care. The aim is to evaluate which method is most feasible in terms of screening uptake to power the main trial (Stage 2), taking into account potential contamination (rates of PSA testing in the control groups) where possible.\n\nThe optimal trial design and Prostate Health Check will be taken forward to Stage 2 for evaluation on a larger group of men. Stage 1 will incorporate a single screening round and Stage 2 will include at least two rounds of screening. \n\nIn parallel, the Transform Discovery Biodigital Twin (BDT) will collect biological specimens to guide translational research and real-time assessment of novel biomarkers.\n\tOther\n\t\n\t\n      ", "condition": "\n\tProstate cancer\n\tCancer\n\t\n      ", "studyDesign": "Randomized controlled study", "overallEndDate": "2027-12-01T00:00:00.000Z", "clinicalTrialsGovNumber": "", "lastUpdated": "2025-12-30T16:41:03.684992283Z", "eligibility": {"inclusion": "Stage 1:\n1. Men in the general population aged 50-74 years.\n2. Additionally, men aged 45-49 years who self-identify in GP practice lists as of Black ethnicity.\n3. Additionally, men aged 45-49 years who are on the GP learning disability Quality Outcome Framework (QOF) register.", "exclusion": "1. History of prostate cancer (clinical diagnosis or histological).\n2. Known history of one or more PSA tests, prostate MRI scans, prostate biomarker tests or prostate biopsies in the preceding 5 years.\n3. Urinary tract infection in the 3 months before screening.\n4. Significant co-morbidities or other cancers likely to impact their life expectancy in the next 10 years.", "ageRange": "Mixed", "gender": "Male", "participantType": "Patient"}, "recruitment": {"recruitmentStart": "2025-11-21T00:00:00.000Z", "recruitmentEnd": "2027-06-01T00:00:00.000Z", "recruitmentStatusOverride": "", "recruitmentStartStatusOverride": "", "targetEnrolment": "16000", "totalFinalEnrolment": "0"}, "countries": ["United Kingdom", "England"], "locations": [{"name": "Imperial College Healthcare NHS Trust", "city": "London", "state": "", "country": "England", "zip": "W2 1BL"}, {"name": "University College London Hospitals NHS Foundation Trust", "city": "London", "state": "", "country": "England", "zip": "NW1 2PG"}], "sponsors": [{"organisation": "Imperial College London", "sponsorType": "University/education", "rorId": "https://ror.org/041kmwe10"}], "funders": [{"name": "Prostate Cancer UK", "fundRef": "http://dx.doi.org/10.13039/501100000771"}, {"name": "National Institute for Health and Care Research"}]}, "studySha256": "f3a313459f0cc127d257541e8428c5abad6a0ef8079aa1cf482b35b5e4dbb67c"}