75400619 true The In Real Life (IRL) Trial: a cluster-randomised controlled trial of a school-based social media reduction intervention versus treatment-as-usual control in secondary school pupils (aged 12–15) in Bradford, UK, and its effects on anxiety (RCADS-25) and secondary outcomes IRL (In Real Life) 1. To estimate the effect of a social media restriction intervention on anxiety (primary outcome) as well as secondary outcomes using a usual-treatment control condition among adolescents in academic years 8, 9, and 10. 2. To explore possible mechanisms underlying the effect of social media restriction. Background and study aims Social media use among children and adolescents has been linked to harms including bullying, sexual risks, and mental health problems. Adolescence is a sensitive period for mental health, with increased risk-taking, ongoing brain development, and the onset of many conditions. Observational studies suggest heavier social media use is associated with more mental health symptoms, but scientific authorities in the UK and US have concluded the average causal effect is unclear. This study is evaluating the effects of an intervention designed to reduce social media media use on mental health among secondary school pupils (academic years 8–10, corresponding to ages 12-15 years). We will explore potential mechanisms underlying these effects. Who can participate? Students enrolled in year 8, 9, or 10 (September 2026), corresponding to ages 12-15 years, at participating secondary schools. What does the study involve? School year groups (academic years 8–10) will be randomly allocated to either (i) a social media restriction app, limiting use to 1 hour per day between 7am and 9pm, or (ii) a treatment-as-usual control condition where the app tracks screen time but applies no restrictions. The intervention will last 6 weeks. Participants will complete a self-reported questionnaire on topics including mental health, bullying, and sleep at baseline (week 0) and follow-up (week 6). Around 30 participants in the intervention group will also take part in qualitative interviews to share their experiences and explore how reducing social media use may affect mental health. What are the possible benefits and risks of participating? Benefits: 1. Possible benefits of the intervention itself (a benefit in terms of mental health). 2. Financial compensation. Risks: 1. Reduced opportunity for social engagement, support, or fear of missing out due to reduced use of social media. 2. Bullying due to participants being left out of social events. 3. Distress experienced during quantitative or qualitative data collection. Where is the study run from? Bradford Teaching Hospitals NHS Foundation Trust (UK) When is the study starting and how long is it expected to run for? September 2026 to May 2027 Who is funding the study? 1. The Wellcome Trust (UK) 2. National Institute for Health Research (UK) Who is the main contact? Dr Dan Lewer, borninbradford@bthft.nhs.uk Anxiety the Revised Child Anxiety and Depression Scale (RCADS-25) anxiety subscale self-report survey week 0 (baseline) and week 6 (follow-up) Symptoms of depression the Revised Children's Anxiety and Depression Scale (RCADS) depression subscale self-report survey week 0 (baseline) and week 6 (follow-up) Mental wellbeing the Short Warwick-Edinburgh Mental Wellbeing Scale (SWEMWBS) self-report survey week 0 (baseline) and week 6 (follow-up) Ethics approval required East of England - Cambridgeshire and Hertfordshire Research Ethics Committee

2 Redman Place

London United Kingdom EC20 1JQ 26/EE/0127 10.1186/ISRCTN75400619 370130 CPMS: 73987, NIHR: 205448, 337689/Z/25/Z, BTHFT 3191 370130 73987 205448 337689/Z/25/Z BTHFT 3191 Interventional Randomized controlled trial Blinded (masking used) Active Parallel Prevention Not applicable 2027-05-31T00:00:00.000Z United Kingdom England Bradford Teaching Hospitals NHS Foundation Trust

Bradford Royal Infirmary Duckworth Lane

Bradford England BD9 6RJ RAE@2.16.840.1.113883.2.1.3.2.4.18.48 true Updated 29/09/2026: Current key inclusion criteria as of 13/08/2026: 1. Currently enrolled in a secondary school 2. In academic year 8 - 10 3. Can speak and read English Previous key inclusion criteria: 1. Currently enrolled in a secondary school 2. In academic year 8 - 10 3. Owns a smartphone (or regularly uses a specific smartphone that can be used in the research) 4. Can speak and read English Child 12 Years 15 Years All 4500 0 No specific exclusion criteria (all school types and young people will be eligible) 2026-09-07T00:00:00.000Z 2027-03-31T00:00:00.000Z Mental health in healthy young people Mental and Behavioural Disorders Study design: This will be a parallel-arm cluster randomised trial in which school year groups will be randomised to two conditions: (1) an intervention involving a smartphone app designed to reduce social media screen time; (2) a treatment-as-usual control state. The primary outcome will be self-reported anxiety, with other outcomes measured by self-report and the app. We will work with 10-12 secondary schools and randomise 30-36 year groups (academic year groups 8-10 only), with baseline measurements taken when participants join the study and follow-up measurements after six weeks. Intervention arm: The intervention will be a smartphone app for Android and iOS (iPhone), which will limit participants’ use of a pre-defined list of social media and internet browser apps. The app will limit social media through two mechanisms: (i) a daily time ‘budget’ across all linked social media apps and (ii) a ‘curfew’ that prevents linked app use during nighttime hours. Based on coproduction with teenagers, we are planning a daily budget of 1 hour and a curfew from 9 pm to 7 am. We will deliver the intervention over 6 weeks. Control arm: Participants download the same app but receive no active intervention components and the app is only used for passive data collection. Randomisation: School year groups will be randomised in a 1:1 ratio to either the intervention or a treatment-as-usual control condition. Year groups will be randomised within schools, meaning each participating school will have at least one intervention and one control year group. Qualitative research: We will also conduct semi-structured interviews with a purposive sample of ~30 intervention participants during the final week of the intervention and at 6-month follow-up. In these interviews we will explore participants’ experiences and mechanisms by which the intervention may influence mental health outcomes. Behavioural The full dataset will be securely stored at Bradford Teaching Hospitals NHS Foundation Trust, with access restricted to IT staff and named researchers (the Chief Investigator, or another senior member of staff if the Chief Investigator leaves). Personal identifiers will be deleted at the earliest opportunity. An analysis dataset will be available upon request using the Born In Bradford data request process: https://borninbradford.nhs.uk/our-data/how-to-access-data/. Data sharing will be subject to an approved analysis plan and data sharing agreement. Available on request Protocol

69da24f6-75f0-4012-b06f-6ecc5bb8cfd6 bdd0a681-de1b-4d1c-afd9-1366e4aa5578 4490397e-b6bc-4614-a9b9-0bd914b346f6 a6b0ed33-75cd-476e-b964-d4f1f137b8d7 c36b5236-1d73-49a4-95cc-b8638c8d7a22 Yes Protocol file ISRCTN75400619_Protocol_v1.3.pdf ecf93d29-c8bb-4b97-a368-d9382ef48f6f true application/pdf 299182 a78c3ca7a064b840428fa9944952089e Dan Lewer https://orcid.org/0000-0003-3698-7196 Public Scientific Principal investigator

Born in Bradford Office Bradford Institute For Health Research Bradford Royal Infirmary Duckworth Lane

Bradford United Kingdom BD9 6RJ +44 (0)1274 274474 borninbradford@bthft.nhs.uk Public Amy Orben https://orcid.org/0000-0002-2937-4183 Principal investigator

MRC Cognition and Brain Sciences Unit University of Cambridge 15 Chaucer Road

Cambridge United Kingdom CB2 7EF +44 (0)1223 355294 info@mrc-cbu.cam.ac.uk Public Bradford Teaching Hospitals NHS Foundation Trust https://ror.org/05gekvn04 Non-commercial Wellcome Trust http://dx.doi.org/10.13039/100010269 National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 61317012 true Long-term effectiveness and implementation of the Creating Active Schools (CAS) programme compared with usual practice on physical activity, health and wellbeing outcomes in primary school children: a mixed-methods natural experimental evaluation. CAS The overall aims of this research are to: 1. Evaluate the sustained implementation, long-term effectiveness and cost-effectiveness of the Creating Active Schools (CAS) programme on children’s physical activity and health and educational outcomes in multi-ethnic and socioeconomically deprived communities. 2. Build a policy, practice and research knowledge mobilisation community to support evidence-informed whole-school physical activity The research aims will be achieved through different research questions which will be answered through work occurring with five different Work packages (WPs). Research Questions: WP1: Evaluating long-term effectiveness of CAS on health & educational outcomes. 1a- In multi-ethnic and socioeconomically deprived primary schools, what is the impact of sustained CAS implementation (up to 7 years) on children’s time spent in MVPA on weekdays? 1b- What is the impact of sustained CAS implementation on secondary outcomes including health, wellbeing and educational outcomes? 1c- Do the effects of CAS on primary and secondary outcomes differ by time, child gender, ethnicity, socioeconomic position, or CAS implementation quality? WP2: Investigating the cost-effectiveness of CAS. 2a- What is the cost-effectiveness of CAS to promote physical activity at school? 2b- What are the expected long-term (lifetime) costs and quality-adjusted survival of sustained CAS implementation? WP3: Assessing the long-term implementation of CAS. 3a- What are the key features and facilitators of high-quality, sustained CAS implementation within primary schools? 3b- How do primary school stakeholders and those implementing CAS perceive the factors influencing sustained whole-school PA? WP4: Integrating implementation & effectiveness data. 4a- To what extent, and how, have the key CAS intervention components contributed to changes in children’s outcomes, and variation therein? WP5: Knowledge mobilisation and dissemination. 5a- To create an effective policy, practice and research community to promote knowledge exchange around whole-school physical activity. 5b- To promote impact in policy, research and practice through effective dissemination of project outcomes. Background and study aims Children’s physical activity is important for physical health, mental wellbeing and learning. However, many children in England do not achieve the recommended 60 minutes of physical activity each day, particularly those living in socioeconomically disadvantaged and ethnically diverse communities. Schools are an important setting for improving physical activity because they reach almost all children. Creating Active Schools (CAS) is a whole-school physical activity programme that helps schools increase opportunities for activity across the school day through changes to school policy, environments, staff practices and activities. This study aims to evaluate the long-term effectiveness, cost-effectiveness and implementation of CAS in primary schools. Who can participate? Primary schools participating in the Creating Active Schools programme and matched comparison schools not involved in CAS can participate. Children in Years 1–3 (approximately aged 5–8 years) attending participating schools will be eligible to take part in study measurements. Parents/carers, teachers and school staff may also take part in questionnaires, interviews and implementation activities. What does the study involve? Intervention schools will continue delivering the CAS programme, while comparison schools will continue usual school practice. The study will collect data during 5-year (2026–2027) and 7-year (2028–2029) follow-up periods. Children will wear a physical activity monitor for seven consecutive days and complete height, weight and waist measurements at school. Parents/carers will complete questionnaires about their child’s physical activity, sleep and wellbeing, and teachers will complete questionnaires about children’s wellbeing and behaviour. The study will also collect information about school physical activity provision, implementation of CAS and school-related costs. Interviews and focus groups will be conducted with school staff and stakeholders to understand how CAS is delivered and sustained over time. Educational outcomes, including attendance and attainment, will also be assessed using routinely collected National Pupil Database data. What are the possible benefits and risks of participating? The study may help schools, researchers and policymakers better understand how schools can support children’s physical activity, health and wellbeing over the long term. Risks are minimal and mainly relate to minor discomfort during physical measurements or inconvenience associated with wearing the physical activity monitor and completing questionnaires. Where is the study run from? The study is coordinated by the University of Bradford in collaboration with the University of Cambridge and the University of York. Data collection takes place in primary schools in Bradford and matched comparison schools in Yorkshire. When is the study starting and how long is it expected to run for? June 2026 to February 2030. Who is funding the study? The study is funded by the National Institute for Health and Care Research Public Health Research Programme (NIHR174726). Who are the main contacts? Professor Andy Daly-Smith University of Bradford A.Daly-Smith@bradford.ac.uk Dr Daniel Bingham University of Bradford d.bingham@bradford.ac.uk Weekday moderate-to-vigorous physical activity (MVPA) in children minutes per day of moderate-to-vigorous physical activity measured using ActiGraph wGT3X-BT accelerometers 5-year follow-up (September 2026–March 2027) and 7-year follow-up (September 2028–March 2029) Habitual total physical activity and sedentary time mean minutes per day of total physical activity and sedentary time measured using ActiGraph wGT3X-BT accelerometers 5-year follow-up (September 2026–March 2027) and 7-year follow-up (September 2028–March 2029) In-school total physical activity and sedentary time mean minutes of total physical activity and sedentary time during school hours measured using ActiGraph wGT3X-BT accelerometers 5-year follow-up (September 2026–March 2027) and 7-year follow-up (September 2028–March 2029) Body mass index (BMI) z-score standardised height (m) and weight (kg) measurements converted to BMI z-scores using UK reference data 5-year follow-up (September 2026–March 2027) and 7-year follow-up (September 2028–March 2029) Waist circumference waist circumference (cm) measured using standardised anthropometric procedures 5-year follow-up (September 2026–March 2027) and 7-year follow-up (September 2028–March 2029) Emotional and behavioural wellbeing teacher-reported Strengths and Difficulties Questionnaire (SDQ) 5-year follow-up (September 2026–March 2027) and 7-year follow-up (September 2028–March 2029) Health-related quality of life EQ-5D-Y and Paediatric Quality of Life Inventory (PedsQL) parent/carer questionnaires 5-year follow-up (September 2026–March 2027) and 7-year follow-up (September 2028–March 2029) Sleep duration parent/carer questionnaire 5-year follow-up (September 2026–March 2027) and 7-year follow-up (September 2028–March 2029) School attendance National Pupil Database records 2016–2029 Key Stage 2 educational attainment in reading, writing and mathematics National Pupil Database records 2016–2029 Ethics approval required Humanities, Social and Health Sciences Research Ethics Panel at the University of Bradford

University of Bradford Richmond Road

Bradford United Kingdom BD71DB E1396    10.1186/ISRCTN61317012 NIHR: 174726 174726 Interventional Non-randomized controlled trial Open (masking not used) Active Parallel Prevention Mixed-methods natural experimental evaluation Not applicable 2030-02-28T00:00:00.000Z United Kingdom England University of Bradford

Richmond Road

Bradford England BD7 1DP 10007785@2.16.840.1.113883.2.1.3.8.2.9.1 true 1. Primary schools participating in the 5-year (2026–2027) and/or 7-year (2028–2029) follow-up evaluation of the Creating Active Schools (CAS) programme 2. Intervention schools delivering CAS since the commencement of Bradford-wide implementation in 2021, or matched control schools not participating in CAS 3. Children enrolled in Years 1–3 at participating schools during the 5-year (September 2026–March 2027) and/or 7-year (September 2028–March 2029) follow-up data collection periods 4. Children aged approximately 5–8 years at the time of participation 5. Written informed consent provided by a parent or legal guardian 6. Age-appropriate child assent provided prior to participation in study procedures Child 5 Years 8 Years All 3000 0 1. Schools not participating in the 5-year (2026–2027) or 7-year (2028–2029) follow-up evaluation of the study 2. Children not enrolled in Years 1–3 at participating schools during the study data collection periods 3. Children without written informed consent from a parent or legal guardian 4. Children who do not provide age-appropriate assent prior to participation 5. Children with medical, physical or educational needs for whom participation in study procedures, including accelerometry or anthropometric measurements, may cause distress or be considered inappropriate or unsafe following discussion with parents/carers and school staff. All children are welcome to take part where participation can be supported safely and appropriately 2026-06-08T00:00:00.000Z 2028-11-30T00:00:00.000Z Prevention of physical inactivity and promotion of health and wellbeing in primary school children living in multi-ethnic and socioeconomically disadvantaged communities. Other The study will conduct a mixed-methods natural experimental evaluation of the long-term effectiveness, cost-effectiveness and sustained implementation of the Creating Active Schools (CAS) programme in primary schools in Bradford. Intervention schools will continue delivery of CAS, a whole-school physical activity programme implemented through an annual cycle of school profiling, Planning for Change, implementation and review, supported by the CAS digital hub, CAS Champions, Communities of Practice and school leadership teams. CAS aims to embed physical activity across school policy, environments, stakeholders and opportunities. Schools have been engaged in CAS since 2021. Control schools will continue with usual practice, including statutory physical education, extracurricular sport and use of PE and Sport Premium funding, but will not participate in CAS or another formal whole-school physical activity programme during the study period. Schools are not randomised, as intervention and matched control schools were identified through an existing quasi-experimental evaluation based on deprivation, ethnic composition and free school meal eligibility. The study includes repeated cross-sectional follow-up data collection at 5-years (September 2026–March 2027) and 7-years (September 2028–March 2029) post-baseline. All children in Years 1–3 at participating schools will be eligible to participate. Physical activity will be assessed using waist-worn ActiGraph accelerometers worn continuously for seven consecutive days. Anthropometric measures will include height, weight and waist circumference collected using standardised procedures. Teachers will complete the Strengths and Difficulties Questionnaire for participating children. Parents/carers will complete questionnaires assessing child physical activity, sleep, health-related quality of life, wellbeing, contextual influences on physical activity and neighbourhood environment characteristics. The study will also include collection of school-level cost and resource-use data to assess cost-effectiveness, alongside qualitative interviews, focus groups, surveys, documentary analysis and implementation assessments with school staff, CAS Champions and wider stakeholders to examine long-term implementation and sustainability. Educational outcomes, including attendance and Key Stage 2 attainment, will be assessed using routinely collected National Pupil Database data. Behavioural Not expected to be made available Protocol

Appendix1_School_InfoForm_CAS

Appendix2_School_InfoForm_Control

Parent_InfoForm_CAS

9df6f6cd-8da2-4669-bec4-366a32607454 693ead26-c226-4931-aa71-5cc27c843d6a f3adfeab-5c35-4838-8605-5a5725304192 0fbad128-892f-4040-b7f1-3e20be9a203d No Protocol file 49504 CAS NIHR Protocol 2026 V1.1_12Feb2026.pdf 791773ed-b63d-4f4e-a714-cf76b204322e true application/pdf 1083128 d1943c1c637b3517caed0291384a16cc Appendix1_School_InfoForm_CAS 49504 Appendix1_School_InfoForm_CAS_NIHR_V1.0 13Mar2026.pdf 9d1834d2-b7e6-476c-a9fa-35da9c81903f true application/pdf 203816 6acd950c634757c6c38e5d608caca261 Appendix2_School_InfoForm_Control 49504 Appendix2_School_InfoForm_Control_NIHR_V1.0 13Mar2026.pdf 0f8b0c9c-09f7-4b74-b6aa-dbec99522a7d true application/pdf 229265 dc62affeef0571f46ebfee5df07973e8 Parent_InfoForm_CAS 49504 Appendix4_Parent_InfoForm_CAS_NIHR_V1.0 13Mar2026.pdf 3525872e-4343-4087-a431-27aa469d2bdc true application/pdf 193033 f875dfc0ad266984c5d4a6b529ce7371 Andy Daly-Smith https://orcid.org/0000-0003-4830-9376 Principal investigator

Institute for Health and Social Care Research University of Bradford Richmond Road

Bradford United Kingdom BD71DP +44 1274 232102 A.Daly-Smith@bradford.ac.uk Public Daniel Bingham https://orcid.org/0000-0002-5809-7357 Scientific Public

Institute for Health and Social Care Research University of Bradford Richmond Road

Bradford United Kingdom BD71DP +44 1274 232102 d.bingham@bradford.ac.uk Public University of Bradford https://ror.org/00vs8d940 Non-commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 10873363 true The Identification of Medication Adherence Barriers Questionnaire intervention (IMAB-Qi): feasibility study to test IMAB-Qi delivery and trial processes in general practice IMAB-Qi - Work Package 3 1. Evaluate the acceptability and feasibility of trial processes, including the recruitment and retention of a representative sample of eligible patients 2. Test procedures for the collection of trial outcome data, and completion rate of blood pressure recordings 3. Evaluate the acceptability and feasibility of embedding IMAB-Qi within MRs 4. Evaluate the acceptability and fidelity of IMAB-Qi delivery, and receipt 5. Test processes for the collection and completeness of health economic data to ensure they are robust and reliable Background and study aims One in two people don’t take their medicines as prescribed for different reasons. Healthcare professionals (HCPs) in general practice surgeries do medication reviews to make sure a patient’s medicines are right for them and support them to take them as prescribed. But patients and HCPs often struggle to work out a person’s main reasons for not taking medicines as prescribed. This makes it difficult for them to find the right solutions. Working with patients, HCPs and researchers, we developed the Identification of Medication Adherence Barriers Questionnaire (IMAB-Q). IMAB-Q has 10 questions for patients to answer before a medication review. Their answers tell the HCP the patient’s main reasons for not taking their medicines as prescribed. Each IMAB-Q question is linked to solutions specific to the reason for not taking medicines as prescribed. These solutions are delivered by the HCP during the medication review. This study aims to test whether the support package that we have developed for general practice teams gives them everything they need to help HCPs to deliver IMAB Qi in their usual medication review processes. We also want to test whether we can collect all the research information that we need to be able to measure whether IMAB-Qi works and is good value for money for the NHS. We will be doing the testing in four general practices across England. This information will mean that we can properly prepare for a larger future trial. Who can participate? Adults who are 18 years and older on the hypertension register can participate as long as they are taking at least one hypertensive medication, have a recent blood pressure reading that exceeds the age-related targets in the National Institute for Health and Care Excellence (NICE) guidelines, are due a medication review at their GP practice during the study period, and do not fall under any of the exclusion criteria. Practice staff will also participate, including HCPs delivering medication reviews and staff involved in the setup of the study and implementation of the intervention at sites. What does the study involve? Ninety-six patient participants will be recruited during the recruitment period, from four participating practices. Patient records will be used to identify eligible patients. Eligible patients will be invited to sign a consent form and complete some questionnaires at baseline, week 1 and week 12; to attend a medication review during the study period and to provide blood pressure readings at three timepoints: baseline, week 4 and week 12. Patient participants will have the option to have their medication review recorded so the researchers can see how the new medication review approach works, and the option to participate in a conversation about their experience with one of the researchers via phone or video link. Some staff participants will set up and deliver the study at their practice, and others will be trained to set up and deliver IMAB-Qi to patients who meet the eligibility criteria. All staff will be invited to complete a demographics questionnaire and to participate in an interview or focus group. What are the possible benefits and risks of participating? There may not be any direct benefits to participants, although participants in the intervention sites may find that they are better supported to take their medications as prescribed. Participants will be helping the research team learn if they can run a bigger study in the future to improve care for people with high blood pressure. The researchers do not think there are any risks in taking part in this study. Where is the study run from? The study is organised and run by a team of researchers in the School of Health Sciences and at the Norwich Clinical Trials Unit, both of which are at the University of East Anglia in Norwich (UK). The University of East Anglia is the Sponsor for the study and has overall responsibility. Other researchers (collaborators) are helping with the study. They are from The University of Leicester, University of York, Brighton and Sussex Medical School, University of Nottingham, North West Surrey Integrated Care Service. The Norfolk and Suffolk ICB are the Host of the study. When is the study starting and how long is it expected to run for? July 2026 to December 2026 Who is funding the study? The study is part of the programme grant funded by the National Institute for Health and Care Research (NIHR) (UK) (PGfAR NIHR206808) Who is the main contact? 1. Prof. Debi Bhattacharya, D.Bhattacharya@uea.ac.uk 2. Dr Sion Scott, Sion.Scott@uea.ac.uk 1. Ability to identify and recruit a representative sample of patients with hypertension willing to consent to take part in the study and study activities across sites, measured using the number of eligible patients identified and invited, the number (and percentage) who agree to enter the study, remain in the study, and complete study activities, including how representative they are of the practice population, measured over the course of the study 2. Ability to collect outcome data, including systolic blood pressure, from patient participants at relevant time points throughout the study, measured using the number (and percentage) who provide valid outcome measure data and health economic data at baseline and 12-week follow-up; completeness of blood pressure data; completeness of routine data collected from medical records; and the proportion who agree to take part in process evaluation activities (having their MR recorded and taking part in an interview with a researcher), measured over the course of the study. 3. Ability to, and acceptability of, embedding IMAB-Qi into primary care patient records and retrieving the data, measured using confirmation that the IMAB-Q questionnaire template has been embedded into the GP clinical records system; that invitations to complete IMAB-Q have been sent from the GP clinical system; the number (and percentage) of patients who complete the IMAB-Q; and through interviews and/or focus groups with patients who receive IMAB-Qi and staff who implement and deliver IMAB-Qi, measured over the course of the study. 4. Fidelity of the delivery of the IMAB-Qi intervention by healthcare professionals (HCPs) measured using a fidelity framework, and its acceptability measured through interviews with patients and HCPs, measured over the course of the study. 1. Health-related quality of life is measured using the EQ-5D-5L questionnaire at baseline and 12-week follow-up 2. Blood pressure is patient-reported at baseline, 4- and 12-week follow-ups and from GP medical records 3. Health and social care resource use is measured using the modified Client Service Receipt Inventory (CSRI) questionnaire and from GP clinical records at baseline and 12-week follow-up 4. Adherence to antihypertensive medication and all other medications measured using a visual analogue scale (VAS) and from GP clinical records at baseline and 12-week follow-up 5. Adverse medicine reactions measured using a bespoke 17-item adverse medicine reaction questionnaire at baseline and 12-week follow-up 6. Intervention appropriateness is measured using the four-item Intervention Appropriateness Measure (IAM) 1 week after the medication review 7. Demographic information is measured using demographic questions at baseline and from GP medical records at baseline 8. Health and health and service care use are measured using data from GP medical records at 12-week follow-up For the intervention group only: 9. Barriers to medication adherence measured using the 10-item IMAB-Q at baseline, 4-week follow-up, and 12-week follow-up 10. Self-enactment of behaviour change techniques (SE BCTs) measured using the SE BCTs questionnaire after the medication review and at 12-week follow-up Old ethics approval format Approved 03/03/2026, Berkshire REC (Health Research Authority, 2 Redman Place, London, E20 1JQ; UK; +44 (0)207 104 8178; berkshire.rec@hra.nhs.uk), ref: 25/SC/0404 10.1186/ISRCTN10873363 355538 CPMS: 68555, NIHR: 206808 355538 68555 206808 Non-randomized study Interventional Non randomised study Treatment 2026-12-31T00:00:00.000Z United Kingdom England Chilwell Valley and Meadows Practice, Chilwell Meadows Surgery

Ranson Road Chilwell Beeston

Nottingham England NG9 6DX C84120001@2.16.840.1.113883.2.1.3.2.4.18.48 MyHealth Group

Southfields Road

Strensall England YO32 5UA The Ridge Medical Practice

Cousen Road

Bradford England BD7 3JX Monkfield Medical Practice

Sackville House Sackville Way Great Cambourne

Cambridge England CB23 6HL RT1CL@2.16.840.1.113883.2.1.3.2.4.18.48 false GP Practices: 1. Have a named clinician who is willing and appropriate to undertake principal investigator responsibility. 2. Suitably trained staff available and willing to set up the study at the site, identify and recruit patient participants and collect and enter data as per protocol. 3. A named person based at the site to support IMAB-Qi implementation of the intervention and staff to support this (intervention sites only). 4. HCPs (pharmacists, doctors, nurses and other team members) with prescribing rights who conduct non-disease-specific MR consultations, available during the recruitment period and willing to deliver IMAB-Qi within their MRs, participate in the study, and undertake the required research-related tasks. 5. Use either SystmOne or EMIS electronic health record system GP practice staff: Staff fulfilling the following criteria will be eligible: 1. The Principal Investigator 2. Staff involved with supporting IMAB-Qi adoption and implementation 3. Staff involved with setting-up and delivering research processes Healthcare professionals (HCPs) involved with IMAB-Qi delivery: HCPs fulfilling the following criteria will be eligible: 1. Have Prescribing rights 2. Conduct MR consultations 3. Willing to deliver IMAB-Qi within their MRs, participate in the study and undertake required research-related training and tasks GP practice patients: 1. Adults aged >=18 years 2. On the hypertension register 3. Current prescription for >=1 antihypertensive medicine(s) prescribed for hypertension for at least the past 4 weeks 4. Blood pressure exceeding their NICE guidelines target for hypertension** 4.1. Aged 18-79 years >=140/90 mm Hg in clinic or >= 135/85 using home blood pressure monitor 4.2. Aged >=80 years >=150/90 mm Hg in clinic or >= 145/85 using home blood pressure monitor 5. Due a MR during the planned study recruitment period **Confirmed after consent Mixed 18 Years 100 Years All 96 0 GP practices: General practices with <5% of their patient population prescribed an antihypertensive medicines Healthcare professionals (HCPs) involved with IMAB-Qi delivery: Healthcare professionals who conduct only disease-specific medication reviews, e.g., annual diabetes reviews Patient participants: 1. Not self-administering their medications 2. Excepted from NICE guideline age-related blood pressure target because it is inappropriate, e.g., receiving end-of-life care, on maximal tolerated doses of medication, declined treatment 3. On the severe mental illness register (IMAB-Q is not validated in this population) 4. Deemed by the practice staff to lack capacity to understand the study and unable to make a decision regarding participating 5. Under the care of a secondary care HCP for treatment of hypertension 6. Pregnant, lactating or known to be planning pregnancy during the study 2026-07-17T00:00:00.000Z 2026-11-30T00:00:00.000Z Cardiovascular, medication non-adherence, hypertension Circulatory System All eligible patients in the IMAB-Qi practices will be offered the Identification of Medication Adherence Barriers Questionnaire intervention (IMAB-Qi). The IMAB-Qi comprises a validated 10-item questionnaire called the IMAB-Q. Each IMAB-Q item represents a potential barrier to a patient taking their medication as prescribed. Each IMAB-Q item is linked to several theory and evidence-based behaviour change techniques (BCTs) that HCPs may deliver to patients within the Medication Review (MR) to address the medication adherence barrier(s) diagnosed by their IMAB-Q responses. Patients will be invited to complete the IMAB-Q prior to their MR using the practice’s usual procedures for collecting information from patients. Health care professionals will review IMAB-Q responses prior to the MR consultation to establish whether the patient is experiencing any barrier(s) to medication adherence, and for identified barriers, HCPs and patients will work together to establish the patient’s medicines to which the barrier(s) relate. Directed by the IMAB-Q, together they will select a BCT to address the barrier(s), and the HCP will deliver it during the MR. For patients where no barriers are identified in the IMAB-Q, the MR will continue without any BCTs being delivered. It is usual practice for HCPs to follow up any patients for whom changes to their care are made during an MR, including delivery of medication adherence support. Therefore, patients who received a BCT in their MR will be followed up as per usual practice. These patients will be sent a repeat IMAB-Q to complete and return before the follow-up appointment. If the repeat IMAB-Q indicates that the barrier(s) have not been addressed, the patient and HCP will explore why and address accordingly (e.g., re-deliver the same BCT(s) or select and deliver alternative BCTs) during the follow-up. For any patients where no barriers were identified using the IMAB-Q, any follow-up would be decided by the HCP and patient. Control: All eligible patients will be offered a usual care MR, and any usual care MR follow ups as deemed necessary and appropriate by the HCP and patient. Behavioural The datasets generated during and/or analysed during the current study will be stored in a publicly available repository: Open Science Framework (https://osf.io/dv7bp). The type of data that will be shared: individual-level data contain the outcome data and baseline characteristics presented in final report When the data will become available and for how long: after publication and in perpetuity By what access criteria the data will be shared, including with whom for what types of analyses, and by what mechanism: free for researchers to use as they wish Whether participants’ consent was obtained for data sharing: yes, participants consented for data to be shared for additional research Comments on data anonymisation, any ethical or legal restrictions, any other comments): all data will be anonymised prior to sharing, and rare events - where fewer than 5 people have a particular value - may be removed from the shared data Stored in publicly available repository Protocol

9a711cb0-759e-45f7-923f-6aba39976e35 3f85b41a-d95c-41af-8c3b-02c786ae6e2a 2a0c0abc-3a14-4530-be84-dd723ba2e06d 004f57f3-c903-4721-b1c3-031736d57b98 Yes Other files 49192_ConsentForm_Patient_V2.1.pdf b3fb969f-d4a9-422a-9714-8117d7ca0add true application/pdf 423337 2a675551d41199e7edf22f45cfa79429 Participant information sheet 49192__PIS_Patient_v2.2.pdf b5c2c925-763f-47cb-ae5b-1ff33afcd0bf true application/pdf 307736 11b84d180c5d93aa2ebcaea3573f0547 Protocol file 49192_PROTOCOL_Feasibility_V3.0.pdf 6dd59f36-786b-4f34-8761-c54829280402 true application/pdf 1357393 c56361465d331299cfc107ee33e672e0 Protocol file ISRCTN10873363_Protocol_Feasibility_v3.4_12Aug2026.pdf 86d5e582-9d81-4c9c-be60-f70cc7dab55f true application/pdf 1366243 086236a1c5ec8d8a069b5ec452237036 Debi Bhattacharya https://orcid.org/0000-0003-3024-7453 Scientific Public Principal investigator

Queen’s Building Office 2.09 School of Health Sciences University of East Anglia Queen’s Building, Norwich Research Park

Norwich United Kingdom NR4 7TJ +44 (0)1603 593391 D.Bhattacharya@uea.ac.uk Public Sion Scott https://orcid.org/0000-0001-7669-0632 Scientific Public Principal investigator

School of Health Sciences University of East Anglia Queen’s Building, Norwich Research Park

Norwich United Kingdom NR4 7TJ +44 (0)1603 591094 sion.scott@uea.ac.uk Public University of East Anglia Hospital/treatment centre https://ror.org/026k5mg93 Non-commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 94157188 true A multicEntre trial to AssesS the validitY of the Kardia six-lead hand-held ECG in psychiatry (Easy ECG V1) Easy ECG V1 1. Compare the diagnostic accuracy of the K6L to the 12L for QT interval in people taking antipsychotic medication. 2. Compare the time to obtain QTc readings between the K6L and 12L – efficiency. 3. Understand the patient acceptability of the K6L compared with the 12L. 4. Using the NICE EVA as reference, determine why and how frequently it is necessary to perform a 12L after a K6L. 5. Describe the prevalence of QT prolongation in patients taking antipsychotics. 6. Understand the clinician acceptability of the K6L. Background and study aims Some medications that are prescribed for patients with mental health problems have side effects that can affect the heart. Doctors use heart tracings called ECGs to understand how the heart is working and ensure it is safe for the person to take these medications. To have a standard ECG, electrode stickers are stuck on the person's chest, wrists and ankles, who then needs to lie still whilst the ECG is recorded. Sometimes, people who need an ECG cannot have it. For example, people who are in distress may not be able to undress or lie still. Sometimes people feel uncomfortable undressing in front of others. Often, NHS clinics do not have the facilities to do ECGs, and the person's GP is asked to do it. Our work has shown that this causes delays in treatment and extra appointments. A new credit-card-sized ECG device (the Kardia 6L [K6L]) has recently been developed. To use it, the person rests two fingers on top of the device and places it so that the back touches the skin of their knee or ankle. The recordings are sent to a phone via Bluetooth. We think the K6L will help more people with mental illness get the ECGs they need. This would help improve safety for people taking medication, reduce the number of appointments and improve the experience for people. We have already shown that the K6L works well in patients seen in a cardiology service. We want to find out how well it works in people seen in mental health services. Who can participate? Patients aged 18 years and over who have been prescribed an antipsychotic medication in any setting What does the study involve? Once consented into the study, participants will first have their demographic information and relevant history recorded. This will be done by reviewing the patient records (notes) and speaking to the participant. Every participant will have their height and weight recorded. Participants will have a 12L ECG followed by a 6L ECG. The 6L should be started as soon as possible after the 12L ECG has been recorded. This time should be no longer than 2 minutes after the 12L has been recorded. The operator will be either a research assistant or a research nurse. At selected sites, a healthcare worker from the participant’s regular clinical team who has been trained to conduct ECGs will carry out the ECGs. The operator of the machines will record the time taken to conduct the 12L from the point that the participant starts to undress or the operator starts to prepare the equipment (whichever comes first). The operator will record the time taken to conduct a 6L starting from the time the operator starts to prepare the equipment. After the ECGs have been take the operator will ask the participant a two-question survey: If you were to have this procedure again with either machine, which test would you choose? What are the reasons you chose [answer from question 1]? What are the possible benefits and risks of participating? We do not anticipate any adverse events in this study. No intervention is being delivered, and data is being collected at one timepoint. Where is the study run from? Leeds Yorkshire Partnership Foundation Trust (UK) When is the study starting and how long is it expected to run for? April 2026 to April 2027 Who is funding the study? Alivecor, Inc. (USA) Who is the main contact? 1. Nazya Azam, nazya.azam@nhs.net 2. Dr George Crowther, georgecrowther@nhs.net QT interval Kardia 6L and standard 12-lead ECG baseline Old ethics approval format Approved 27/10/2025, HRA and Health and Care Research Wales (HCRW) (2 Redman Place, Stratford, London, E20 1JQ, UK; Tel: not available; approvals@hra.nhs.uk), ref: 25/YH/0173 10.1186/ISRCTN94157188 356658 CPMS: 61500 356658 61500 Non-randomized study Interventional Non randomised study Treatment 2027-04-01T00:00:00.000Z United Kingdom England Leeds and York Partnership NHS Foundation Trust

St. Marys House St. Marys Road

Leeds England LS7 3JX RGD@2.16.840.1.113883.2.1.3.2.4.18.48 Tees, Esk and Wear Valleys NHS Foundation Trust

Trust Headquarters West Park Hospital Edward Pease Way

Darlington England DL2 2TS RX3@2.16.840.1.113883.2.1.3.2.4.18.48 Kent and Medway Mental Health NHS Trust

Farm Villa Hermitage Lane

Maidstone England ME16 9PH RXY@2.16.840.1.113883.2.1.3.2.4.18.48 Essex Partnership University NHS Foundation Trust

The Lodge Lodge Approach Runwell

Wickford England SS11 7XX R1L@2.16.840.1.113883.2.1.3.2.4.18.48 Humber Teaching NHS Foundation Trust

Trust Hq Block a Willerby Hill Beverley Road Willerby

Hull England HU10 6ED RV9@2.16.840.1.113883.2.1.3.2.4.18.48 Bradford District Care NHS Foundation Trust

New Mill Victoria Road Saltaire

Shipley England BD18 3LD TAD@2.16.840.1.113883.2.1.3.2.4.18.48 Cambridgeshire and Peterborough NHS Foundation Trust

Elizabeth House Fulbourn Hospital Fulbourn

Cambridge England CB21 5EF RT1@2.16.840.1.113883.2.1.3.2.4.18.48 Surrey and Borders Partnership NHS Foundation Trust

18 Mole Business Park Randalls Road

Leatherhead England KT22 7AD RXX@2.16.840.1.113883.2.1.3.2.4.18.48 Hampshire and Isle of Wight Healthcare NHS Foundation Trust

Tatchbury Mount Hospital Calmore

Southampton England SO40 2RZ RW1@2.16.840.1.113883.2.1.3.2.4.18.48 false Any patient prescribed or due to be prescribed an antipsychotic medication in any setting (ward or outpatient) Mixed 18 Years 100 Years All 800 0 1. Aged under 18 years old 2. Patients who lack capacity and do not have a personal consultee to give advice or where the personal consultee does not think they would want to take part 2025-12-04T00:00:00.000Z 2027-04-01T00:00:00.000Z Cardiovascular and mental health Circulatory System We will conduct a multi-centre study comparing K6L vs 12L ECGs in people receiving antipsychotic therapy. There will be ten NHS sites in total. Our sites span England and Wales and serve a range of rural, urban and semi-rural communities. This will allow us to ensure participants are from a wide range of socioeconomic and ethnic backgrounds. Duration is eighteen months in total (3 months set up, 12 months data collection, 3 months analysis and write up). Recruitment will take place in any clinical area where antipsychotic treatments are prescribed (outpatient or inpatient) in eligible people. Study procedures consist of one 12L ECG and one KardiaMobile 6L ECG per participant, recorded sequentially by the same individual. The 6L should be started as soon as possible after the 12L ECG has been recorded. This time should be no longer than 2 minutes after the 12L has been recorded. Once consented into the study, participants will first have their demographic information and relevant history recorded. This will be done by reviewing the patient records (notes) and speaking to the participant. Demographic information: 1. Age 2. Gender at birth 3. Ethnicity 4. Height 5. Weight History: 1. Primary psychiatric diagnosis for which the antipsychotic is prescribed for 2. Other psychiatric diagnoses 3. Current antipsychotic treatment – type/types of antipsychotic, dose and administration route 4. Other prescribed medications that can impact QT interval 5. Cardiovascular history The 12L will be collected using a MAC 550 (GE Healthcare, WI, USA) or equivalent recorder (calibrated as per machine standards). The 6L will be collected using an Alivecor Kardiamobile 6-lead ECG machine. The operator will be either a research assistant or research nurse. At selected sites (Leeds, Hull, Tees Esk and Wear Valleys (TEWV) and Kent), a healthcare worker from the participant's regular clinical team who has been trained to conduct ECGs will carry out the ECGs. The operator of the machines will record the time taken to conduct the 12L from the point that the participant starts to undress or the operator starts to prepare the equipment (whichever comes first). The operator will also record the time taken to conduct a 6L starting from the time the operator starts to prepare the equipment. After the ECGs have been take the operator will ask the participant a two-question survey: 1. If you were to have this procedure again with either machine, which test would you choose? 2. What are the reasons you chose the [answer from question 1]? Participant survey data will be analysed to understand patient acceptability. A simple count will be used to demonstrate preference between the devices (survey question 1). Content analysis will be used to illustrate the reasons behind this decision and a list of the top 5 reasons for the preference will be created for each type of machine. Healthcare worker time to treatment and ECG quality analysis: At selected sites (Leeds, Kent, Hull and TEWV), 80 ECGs will be collected by a member of the participant's usual treating team who has been trained to use K6L and 12L ECGs. This is to test whether there is a difference in time taken to complete the ECGs and the K6L ECG quality when ECGs are completed by a researcher compared to the usual treating team (real world setting). The data recorded will be identical to the data collection set out above, except that the person conducting the ECG will be asked to indicate which ECG they prefer and why (objective 6). The ECGs will be graded by independent observers who are blinded to the patient and patient details. Noise on ECG will be described according to a noise score (NS) where NS 1 is a completely clear ECG, NS 2 is an ECG with noise but where a good interpretation was possible, NS 3 borderline ECG for noise (analysis based on RR regularity), and NS 4 is not interpretable. K6L validation: The automated QT and QTc analysis will be recorded. This data will be available to the clinical team to aid patient management. Additionally, all other automated intervals will be recorded, e.g. PR interval. Statistical analysis will be performed (Bland Altman and regression analysis) to compare the differences in these results between the 12L versus the K6L for QT, QTc and PR intervals in leads I, II, and AvL. Equivalence of the measurements using the two methods will be carried out using standard equivalence testing methods at a 5% level of significance, with 95% limits of agreement reported. Time to obtain ECG reading: Statistical analysis will be performed to compare the time taken to complete the 6- and 12-lead ECGs. Two separate analyses will be reported: 1. The difference in time when the ECGs are performed by a research assistant. 2. The difference in time when the ECGs are performed by a member of the clinical team (who has been trained to conduct ECGs). Frequency of the need to repeat ECG following K6L: From the 6L data only, using the NICE early valuation assessment criteria for when a repeat QT interval measurement using a 12-lead electrocardiogram (ECG) device is offered following a 6-lead ECG*, we will report the number and proportion of times it would be necessary to complete a 12 Lead ECG following a 6-lead ECG. *When QTc interval is > 440 in men or >470 in women. Prevalence of QT prolongation: The whole cohort will be used to demonstrate the prevalence of QT prolongation in (>440 in men, >470 in women) in people taking antipsychotics. We will also use the data to demonstrate any dose-related effects of antipsychotics on QT (total daily antipsychotic dose as an equivalent to haloperidol vs QTc), and any differences in QTc dependant on antipsychotic type or administration route. All prevalence data will be displayed as a percentage. Recruitment: Potential participants will be identified by their clinical care team, in conjunction with local site research assistants or research nurse (depending on site preference). A research assistant or research nurse (depending on site preference) at each site will recruit 80 participants from both wards and outpatient clinics. The research assistant/nurse will provide the participant information sheet and explain the study. We will work with our PPI group to ensure these materials are understandable and provide easy read versions. Furthermore, we have budgeted for services to translate patient information where necessary. It is hoped that participants will be recruited on the same day, but where necessary they will be given time to consider participation or discuss it with family and friends. Where potential participants lack capacity to consent, personal consultees will be approached on their behalf. Patients who do not wish to participate will receive treatment as usual. ECG registry: Every recruited patient will have the opportunity to opt into a long-term registry. Consent will be obtained to enable the study team to collect adverse cardiac event data and details of the psychotropic prescriptions from hospital or GP records for 10 years. Other Data sharing statement to be made available at a later date 77a68d28-9476-4e3d-9bd5-7e3e6d15a7ec 8b50210b-6e32-4731-9612-ee1882789b29 81826f35-0404-45cc-9d0b-18bac5540999 74e2c6f7-2959-4fd6-86be-20464f387187 No Nazya Azam Scientific

Leeds and York Partnership NHS Foundation Trust, 1st Floor, Main House, St Mary's House

Leeds United Kingdom LS7 3JX +44 (0)7980 958984 nazya.azam@nhs.net Public George Crowther Scientific

Liaison Psychiatry for Older People, Beckett Wing, St James's Hospital

Leeds United Kingdom LS9 7TF +44 (0)7703288239 georgecrowther@nhs.net Public Leeds and York Partnership NHS Foundation Trust Hospital/treatment centre https://ror.org/00n635c12 Non-commercial Alivecor, Inc. 49481858 true A cluster randomised controlled trial of online Acceptance and Commitment Training (ACT) to improve mental wellbeing in staff caring for terminally ill people and their caregivers RESTORE The primary objective is to evaluate the efficacy of RESTORE plus usual support for staff mental wellbeing in comparison to usual support alone at week 24 (12 weeks post-intervention completion). The secondary objectives are to evaluate the efficacy of RESTORE plus usual support, in comparison to usual support alone in improving staff burnout, depression, anxiety and stress; and reducing intention to leave at week 24 (12 weeks post-intervention completion). Background and study aims Hospice staff working in palliative care often face high levels of stress and emotional strain. However, there’s a lack of proven psychological support to help them cope. In 2021, a small pilot study tested an online training programme called RESTORE (Research Evaluating Staff Training Online for Resilience), based on Acceptance and Commitment Training (ACT). The results were promising, but more research is needed. This new study will test whether RESTORE really helps improve staff wellbeing compared to the usual support available in hospices. Who can participate? Staff working in hospices that agree to take part in the study can join. They’ll need to discuss participation with their line manager to make sure it fits around their work schedule. What does the study involve? Hospices will be randomly assigned to either receive the RESTORE training or continue with their usual wellbeing support. Participants in the RESTORE group will: -Attend four live online workshops (each about 1.5 hours) -Spend around 8–10 hours over eight weeks doing self-guided learning using videos, audio, and workbook exercises Participants in the control group will continue using their usual wellbeing resources (like webinars and self-help tools) and will be offered RESTORE training later. All participants will complete online questionnaires at four points: before the study starts, and then 8, 12, and 24 weeks later. Some may also be invited to take part in an interview to share their experience. What are the possible benefits and risks of participating? Taking part may be enjoyable and helpful, and could improve wellbeing. The information gathered will help improve future support for hospice staff. There are no expected risks, but participants will need to make time for the training and questionnaires. If anyone feels more stressed during the study, a trial therapist will be available to offer guidance and suggest further support. Where is the study run from? Edinburgh Clinical Trials Unit (UK) When is the study starting and how long is it expected to run for? February 2025 to February 2028. Who is funding the study? The study is funded by the National Institute for Health and Care Research – Efficacy and Mechanism Evaluation programme (UK) Who is the main contact? RESTORE.trial@ed.ac.uk Mental wellbeing will be measured using the Warwick Edinburgh Mental Wellbeing scale at recruitment, 8 weeks, 12 weeks and 24 weeks 1. Burnout will be measured using the Burnout Assessment Tool – Short Form at recruitment, 8 weeks, 12 weeks and 24 weeks 2. Depression, anxiety and stress will be measured using the Depression, anxiety and stress scale at recruitment, 8 weeks, 12 weeks and 24 weeks 3. Thoughts about leaving – past 3 months will be measured by a single item question at recruitment and 24 weeks 4. Intention to leave – future will be measured by a Four item scale at recruitment and 24 weeks 5. Psychological flexibility – healthcare professional will be measured by Mindful Healthcare Scale at recruitment, 8 weeks, 12 weeks and 24 weeks 6. Psychological flexibility – general will be measured by Psy-Flex at recruitment, 8 weeks, 12 weeks and 24 weeks 7. Occupational stress will be measured by Occupational Stress Scale for Palliative Care at recruitment and week 24 8. Stress prone thinking style will be measured by Anxious Thoughts and Tendencies Scale at recruitment, 8 weeks, 12 weeks and 24 weeks 9. Wellbeing resource engagement will be measured by Wellbeing resource engagement questionnaire at 8 weeks, 12 weeks and 24 weeks Ethics approval required School of Health in Social Science

The University of Edinburgh, Medical School, Doorway 6, Teviot Place

Edinburgh United Kingdom EH89AG 24-25CLPS140 10.1186/ISRCTN49481858 360616 CPMS: 69383 360616 69383 Multicenter cluster randomized controlled trial Interventional Cluster randomised trial Quality of life Other 2028-02-29T00:00:00.000Z United Kingdom England Sue Ryder

Leckhampton Court Hospice Church Road

Cheltenham England GL53 0QJ Compton Palliative Care Team

Compton Hospice Ltd, Compton Hall 4 Compton Road West

Wolverhampton England WV3 9DH Y03018@2.16.840.1.113883.2.1.3.2.4.18.48 Countess Mountbatten Hospice (botley Road)

Botley Road West End

Southampton England SO30 3JB GAX01@2.16.840.1.113883.2.1.3.2.4.18.48 Douglas Macmillan Hospice

Barlaston Road Blurton

Stoke-on-trent England ST3 3NZ M83704@2.16.840.1.113883.2.1.3.2.4.18.48 Francis House Childrens Hospice

390 Parrswood Road Didsbury M20 5NA

Didsbury England M20 5NA Hospiscare

Searle House Dryden Road

Exeter England EX2 5JJ Y06114@2.16.840.1.113883.2.1.3.2.4.18.48 Rowans Hospice

Purbrook Heath Road Purbrook

Waterlooville England PO7 5RU 5FEA8@2.16.840.1.113883.2.1.3.2.4.18.48 Weston Hospicecare

Jackson Barstow House 28 Thornbury Road Uphill

Weston-super-mare England BS23 4YQ 11TDL@2.16.840.1.113883.2.1.3.2.4.18.48 The Myton Hospices

Clifford Bridge Road Coventry

Coventry England CV2 2HJ Dorothy House Hospice

Dorothy House Hospice Care Winsley

Bradford-on-avon England BA15 2LE Y06323@2.16.840.1.113883.2.1.3.2.4.18.48 Katharine House Hospice

Weston Road

Stafford England ST16 3SB Y06730@2.16.840.1.113883.2.1.3.2.4.18.48 St Anns Hospice

St. Anns Road North Heald Green

Cheadle England SK8 3SZ 5F786@2.16.840.1.113883.2.1.3.2.4.18.48 Bolton Hospice

Queens Park Street Off Chorley New Road

Bolton England BL1 4QT P82654@2.16.840.1.113883.2.1.3.2.4.18.48 Tapping House

Wheatfields Hillington

King's Lynn England PE31 6BH 07JTH@2.16.840.1.113883.2.1.3.2.4.18.48 East Cheshire Hospice

Millbank Drive

Macclesfield England SK10 3DR 8DC39@2.16.840.1.113883.2.1.3.2.4.18.48 St Catherine's Hospice

St Catherine’s Park Lostock Lane, Lostock Hall

Preston England PR5 5XU Rainbows Hospice

Lark Rise

Loughborough England LE11 2HS Y08527@2.16.840.1.113883.2.1.3.2.4.18.48 Beaumond House Hospice Care

32 London Road

Newark England NG24 1TW VM9VC@2.16.840.1.113883.2.1.3.2.4.18.48 Springhill Hospice

Broad Lane

Rochdale England OL16 4PZ 8DK70@2.16.840.1.113883.2.1.3.2.4.18.48 St Catherine's Hospice

Grace Holland Avenue Pease Pottage

Crawley England RH11 9SL Employee Health professional 1. Doctors 2. Nurses 3. Health Care Assistants 4. Social workers and members of the social work team 5. Allied health professionals 6. Staff offering community-based palliative care (e.g. community palliative care clinical nurse specialists; and health care assistants providing overnight end-of-life home care) Mixed 18 Years 100 Years All 300 0 1. Staff currently in receipt of any psychological therapy intervention (either in work or outside of work). 2. Staff who have completed a psychological therapy intervention within the last three months. If potential participants have received psychological therapy intervention, but this ended over three months prior to enrolment, they will be eligible to enrol in RESTORE 2025-10-01T00:00:00.000Z 2026-06-30T00:00:00.000Z Mental wellbeing in staff working in hospices Other Hospices will be randomised to either intervention or control. Randomisation allocation will not be undertaken until sites and participants are enrolled and baseline assessments have been completed; only then will the site be randomised by the trial management team. No participants can be enrolled after the site has been randomised. Participants in the intervention arm will attend four live online workshops (approx. 1.5 hours each) and will commit approximately eight to ten hours of engagement over eight weeks, of self-directed learning and skills practice using video, audio, and workbook exercises. Participants will be reminded by email about routinely available wellbeing support resources available to them through their organisation. These resources typically include information and education in the form of free self-care webinars, self-help and online mental health tools. Participants in the control arm will be offered the RESTORE training at a later date. Participants will complete online questionnaires at the following timepoints: - Baseline, - 8 weeks) after baseline - 12 weeks after baseline - 24 weeks after baseline Behavioural The de-identified dataset will be retained at the end of the trial, for a minimum of the proscribed retention period. During this time it will be available for sharing, post initial results/publication embargo. All requests for data will have to be approved by the Edinburgh Clinical Trail Unit's data sharing committee who will check appropriateness of requests. Available on request

64dcb252-cdd4-42b9-8db7-9c9b1e368b66 524f13c6-09d9-4a54-9db3-ed32ff60639e 63c81b9d-890c-4c7b-a620-3690c0c73296 68cd383e-464a-4a78-bb00-20014e437099 ebe69adb-2ad4-41a5-923b-03ce75b21ff0 Yes Participant information sheet 47866 RESTORE Participant Information Sheet v1.0 17Jul2025.pdf 7248e603-fd14-4aa0-ac1d-f029b65bbb5c true application/pdf 455876 4c6c1ef3a4278e651158ca35e877326c Alix Macdonald https://orcid.org/0009-0004-5130-9582 Public

Usher Building 5 Little France Rd

Edinburgh United Kingdom EH16 4UX +44 131 651 9928 restore.trial@ed.ac.uk Public David Gillanders https://orcid.org/0000-0003-4071-4211 Scientific Principal investigator

University of Edinburgh School of Health in Social Science Elsie Inglis Quad Teviot Place

Edinburgh United Kingdom EH8 9AG +44 131 651 3946 david.gillanders@ed.ac.uk Public Anne Finucane https://orcid.org/0000-0002-3056-059X Scientific Principal investigator

University of Edinburgh Doorway 6, Medical School Teviot Place

Edinburgh United Kingdom EH8 9AG +44 131 651 3946 a.finucane@ed.ac.uk Public University of Edinburgh University/education https://ror.org/01nrxwf90 Non-commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 84780524 true A quasi-experimental evaluation of the effectiveness of a community-based breastfeeding support intervention in promoting breastfeeding rates at 6-8 weeks postpartum in the Better Start Bradford cohort. Primary Hypothesis Participation in the BFS intervention will increase the likelihood of any form of breastfeeding at 6–8 weeks postpartum compared to standard care in the Better Start Bradford (BSB) cohort. Secondary Hypotheses Exclusive Breastfeeding: Participation in the BFS intervention will increase the likelihood of exclusive breastfeeding at 6–8 weeks postpartum compared to standard care. Any Breastfeeding: Mothers who receive the BFS intervention will have higher rates of any breastfeeding at 6 months postpartum compared to those receiving standard care. Pre- vs. post-pandemic comparison: The rate of exclusive breastfeeding at 6-8 weeks postpartum will be higher among mothers who received in-person BFS support pre-pandemic, compared to those who received virtual/telephone BFS support during the pandemic. Intervention Dose: A higher number of support contacts (intervention dose) will be associated with a greater likelihood of any and exclusive breastfeeding at 6–8 weeks postpartum. Delivery Format: Breastfeeding rates at 6-8 weeks postpartum will be higher among mothers who received in-person BFS support compared to those who received telephone support (independent of pandemic) Interpreter Use: Mothers who require an interpreter will have lower breastfeeding rates at 6–8 weeks postpartum compared to those who did not. Participant Characteristics: Mothers with English as a second language will have lower breastfeeding rates at 6–8 weeks to native English speakers. Background and study aims This study will explore whether a community-based programme to provide breastfeeding Support to new mothers in the Better Start Bradford area helps them to continue breastfeeding their babies 6 to 8 weeks after birth, compared to not if they did not get the support. Research shows that breastfeeding has many benefits for both mothers and babies, but the UK has some of the lowest rates of breastfeeding in the world. Many women stop breastfeeding earlier than they would like to, often due to a lack of timely support. The Breastfeeding Support programme was established to address this by offering direct and emotional support to new mothers through trained breastfeeding support workers. The service was also adaptable, with face-to-face, phone calls, or video calls. During the COVID-19 pandemic, however, support was entirely phone and video contact. The main question is whether women who received support through the programme were more likely to be still breastfeeding at 6–8 weeks compared to similar women who did not receive the intervention. It also explores whether the programme helped with exclusive breastfeeding (where babies receive only breast milk), whether its impact lasted until six months, and whether changes in how the service was delivered during the pandemic affected its success. The study will also check if results are different based on the format of the support (in-person or remote), the spoken primary language of the woman, or their need for an interpreter. Who can participate? Mothers (>18 years) who participated in the Breastfeeding Support intervention with at least one support contact, completed the BSB BiBBS baseline questionnaire (the consent and baseline data cohort), and neither mother nor baby was admitted to the ICU/NICU after delivery. What does the study involve? For this, researchers are using existing data from a large local project called Born in Bradford’s Better Start (BiBBS), which has tracked the health and experiences of thousands of mothers and babies over approximately 10 years. Some mothers in BiBBs received the Breastfeeding Support intervention, and some did not. By using a method called propensity score matching, the researchers will compare women who are similar in key characteristics, such as age, ethnicity, breastfeeding intentions, and depression. Data to support this study comes from three main sources: a questionnaire completed by mothers during pregnancy, service records from the Breastfeeding Support programme, and health visitor records documenting how babies were fed at 6–8 weeks and 6 months. In addition to analysing whether the programme helps to promote breastfeeding, the team will consider the cost of delivering the programme. They will compare those costs with the known long-term health benefits of breastfeeding to estimate whether the programme offers good value for money. The evaluation does not involve new data collection; it uses data already gathered through routine care and the BiBBS cohort. Ethical approval for this kind of research was granted when the BiBBS study began, and strict data privacy procedures are followed. The results of the study will be shared through scientific publications, community newsletters, social media, and other public channels. The goal is to provide useful insights for healthcare providers, local services, and decision-makers about whether this kind of community support program should be continued or expanded. What are the possible benefits and risks of participating? There are no anticipated additional risks or benefits, as all processes are part of standard midwifery care, and all data collection has been undertaken as part of the existing BiB/BiBBS studies. Any potential risks from participants completing mental health measures are mitigated through those collecting the measures being trained in Good Clinical Practice, and by providing opportunities for signposting to relevant services. Where is the study run from? Better Start Bradford, Better Start Bradford Innovation Hub (UK) When is the study starting and how long is it expected to run for? November 2015 to March 2024 Who is funding the study? The National Lottery Community Fund (UK) Who is the main contact? Behnam Tajik, behnam.tajik@york.ac.uk Any breastfeeding at 6–8 weeks postpartum is measured using linked routine data collected from health visitor records (SystmOne) at one time point (the mandated 6-to-8-week review). This is recorded as a binary measure (any breastfeeding = 1 / no breastfeeding = 0). 1. Exclusive breastfeeding at 6–8 weeks postpartum is measured using linked routine data collected from health visitor records (SystmOne) at one time point (the mandated 6-to-8-week review). Binary measure: exclusive breastfeeding = 1 / not exclusive = 0. 2. Any breastfeeding at 6 months postpartum is measured using linked routine data collected from health visitor records (SystmOne) at one time point (6-month health-visitor contact). Binary measure: any breastfeeding = 1 / no breastfeeding = 0. Subgroup / secondary analyses: 1. Impact of intervention delivery mode: compare outcomes by delivery mode (face-to-face vs telephone/virtual). Analysis: stratified and interaction analysis within logistic regression models (treatment × mode). 2. Dose–response (number of support contacts): correlation between number of BFS contacts and breastfeeding outcomes; modelled as both continuous and categorised (e.g., above/below median) covariate; trend tests and marginal effects reported. 3. Interpreter use: compare outcomes for participants where an interpreter was used vs not used; adjusted logistic regression and subgroup checks. 4. English language proficiency: subgroup difference (English first language vs English second language); adjusted models and interaction tests. 5. Pre- vs post-pandemic implementation effects: compare outcomes for participants who received the intervention pre-COVID (in-person) vs during COVID (telephone/virtual), including an assessment of the implementation period as an effect modifier. 6. Cost-effectiveness / economic threshold analysis: planned cost analysis of programme delivery costs plus a threshold analysis linking plausible long-term health benefits to cost-effectiveness (NICE Reference Case framework used where possible). This will be described at a high level in the registry; detailed methods will be in the analysis plan. Ethics approval required Yorkshire & The Humber - Bradford Leeds Research Ethics Committee

Room 001, Jarrow Business Centre, Viking Industrial Park Rolling Mill Road

Jarrow United Kingdom NE32 3DT 15/YH/0455 10.1186/ISRCTN84780524 188581 CPMS: 30638 188581 30638 Quasi-experimental evaluation using propensity score matching to compare intervention participants with matched controls Interventional Non randomised study Efficacy 2024-03-31T00:00:00.000Z United Kingdom England Better Start Bradford

Bradford United Kingdom BD5 9NP Service user 1. Mothers who participated in the Breastfeeding Support intervention with at least one support contact 2. Completed BSB BiBBS baseline questionnaire (the consent and baseline data cohort) 3. Neither mother nor baby was admitted to the ICU/NICU after delivery Adult 18 Years Female 1186 1770 1. Mothers who did not complete the BSB and BiBBS baseline questionnaire 2. Mothers or babies admitted to the ICU/NICU post-delivery 2018-10-01T00:00:00.000Z 2024-03-31T00:00:00.000Z Maternal and child health, specifically focusing on: Breastfeeding support Breastfeeding rates at 6–8 weeks and 6 months postpartum Pregnancy and Childbirth This is a quasi-experimental evaluation using propensity score matching to compare intervention participants with matched controls within the Born in Bradford Better Start cohort. Participants in the Breastfeeding Support (BFS) Programme are typically enrolled shortly after birth, with the first support contact ideally occurring within the first few days postpartum. The BFS Programme is a community-based behavioural intervention designed to promote and sustain breastfeeding among new mothers. It is particularly relevant in communities with lower breastfeeding rates and among groups who may face social, cultural, or language-related barriers to sustained breastfeeding. The programme is delivered by trained Breastfeeding Support Workers (BSWs), who provide both practical and emotional support tailored to each mother’s needs. Support is offered in a flexible format, including face-to-face home visits, community-based sessions, and telephone or video calls. Each mother receives at least one contact with a BSW, and the number of subsequent contacts varies depending on individual needs. The support includes guidance on breastfeeding techniques, managing common breastfeeding challenges, and encouragement to help mothers meet their breastfeeding goals. In the Better Start Bradford (BSB) area, the BFS Programme was adapted in response to the COVID-19 pandemic in March 2020. All support transitioned to telephone or video delivery during the pandemic period, before gradually returning to a mixed model that included face-to-face support. Study outcomes are drawn from routine data collected through the Born in Bradford’s Better Start (BiBBS) cohort. These include questionnaire data collected during pregnancy, BFS service records documenting support contacts, and health visitor records on infant feeding status at 6–8 weeks and 6 months postpartum. As all data are derived from routine sources, no additional data collection is required for the evaluation. If a participant has relevant data recorded in more than one source, the BiBBS dataset will be prioritised. Behavioural Researchers are encouraged to make use of the BiB data, which are available through a system of managed open access. Before contacting the researchers, please read the Guidance for Collaborators (https://borninbradford.nhs.uk/research/guidance-for-collaborators/). The BiB executive reviews proposals monthly and will endeavour to respond to requests as soon as possible. Find out about the different datasets in the Data Dictionary (https://borninbradford.github.io/datadict/) or contact a member of the BiB team (borninbradford@bthft.nhs.uk). Once you have formulated your request, please complete the ‘Expression of Interest’ form available here (https://borninbradford.nhs.uk/wp-content/uploads/BiB_EoI_v3.1_10.05.21.doc) and send it to borninbradford@bthft.nhs.uk. If the request is approved, you will be asked to sign a Data Sharing Contract (https://borninbradford.nhs.uk/wp-content/uploads/BIHR-Data-Sharing-Contract.docx) and a Data Sharing Agreement (https://borninbradford.nhs.uk/wp-content/uploads/BIHR-Data-Sharing-Agreement.docx), and if the request involves biological samples, you will need to complete a material transfer agreement (https://borninbradford.nhs.uk/wp-content/uploads/BiB-Material-Transfer-Agreement-v4-0.docx). Born in Bradford (BiB) is a longitudinal research project. BiB aims to work out why some people have good health or well-being, while others have difficulties. To do this, BiB collects information from participants about all aspects of their lives at different ages using surveys, research clinics and other assessments. BiB also gathers information about families from other sources, such as health records or environmental records. BiB processes the data to make sure it is accurate, well organised, and to make it so that no person can be identified from the data. BiB then shares this processed data with scientists conducting research with potential public benefit. These scientists can be based anywhere in the world. The data that is available to be shared can be seen here: https://borninbradford.github.io/datadict/bibbs/. Available on request Protocol

Statistical Analysis Plan (SAP) & Open Science Framework (OSP)

Study website Migrated from study website field

8790ee74-ebaf-41c1-a358-d7016227fdb5 3ee988e2-c212-4251-bddc-1243b9ce4bc2 cfac48d3-5a15-4d8e-a7e9-4b463efcb80a 2aa4e589-e935-4f0f-9a44-8725f4a81d6c Yes Protocol file 47800_Protocol_V1.0_23July2025.pdf ba043ace-cfe8-4f49-82a7-a04e1ac3b351 true application/pdf 618648 b97b348a700b0587f2a8c75a78bbdc1f Statistical Analysis Plan (SAP) & Open Science Framework (OSP) 47800_SAP.pdf e7447799-86ea-4ac2-9b4a-7b1366208835 true application/pdf 196555 3027178dc5dabfa2432389802da8a949 Maria Bryant https://orcid.org/0000-0001-7690-4098 Public Principal investigator

University of York Heslington

York United Kingdom YO10 5DD +44 (0)1904 321321 maria.bryant@york.ac.uk Public Behnam Tajik https://orcid.org/0000-0002-8453-3909 Scientific

University of York Heslington

York United Kingdom YO10 5DD +44 (0)1904 321321 behnam.tajik@york.ac.uk Public Bradford Teaching Hospitals NHS Foundation Trust Hospital/treatment centre https://ror.org/05gekvn04 Non-commercial National Lottery Community Fund http://dx.doi.org/10.13039/501100013529 32222362 true Evaluating the indoor environment, health, carbon emission, economic outcomes of retrofitting social housing properties to improve energy efficiency in a low-income multi-ethnic population: a quasi-experimental study with process evaluation Healthy Homes We aim to assess the impact of improving the energy efficiency of social housing ('retrofit') on indoor environmental quality (including temperature, relative humidity, damp/mould, and indoor air quality (e.g. NO2, PM2.5, carbon dioxide [CO2]), health, and environmental and economic impacts. We will explore trade-offs in indoor conditions and other potential unexpected consequences, along with contextual and system factors which affect implementation and resident experience. Our research questions (RQ) are: RQ1: What is the impact of retrofit up to 12 months post-retrofit on: A) temperature, B) thermal comfort, C) indoor air quality (focusing on NO2, PM2.5, and air change rates) D) risk of damp/mould; E) energy use, F) self-reported satisfaction and mental and respiratory health? RQ2: A) What is the impact of retrofit up to 5 years post-retrofit on adult residents’ acute health care use related to i) mental health, ii) respiratory health, and iii) cardiovascular health?; B) Are there differential impacts for vulnerable groups (those with pre-existing health issues)? RQ3: What is the impact of retrofit on short- and long-term A) exposure to indoor environmental conditions and carbon emissions (3A), and B) health and economic impacts? (3B) RQ4: A) How was the retrofit implemented, and what system, and wider contextual factors influenced the implementation? B) Was the implementation as intended (from the perspective of residents and other stakeholders) and are there any unexpected consequences from implementation? Background and study aims The quality of our homes can have a big impact on our health. Cold, damp, or poorly ventilated homes can lead to problems like mould, indoor air pollution, and stress, which may increase the risk of heart and lung conditions. Making homes more energy-efficient—known as retrofitting—can help improve health, reduce energy bills, and lower carbon emissions. However, if not done carefully, retrofitting could also reduce fresh air and make damp or pollution worse. This study is working with a large social housing provider in Bradford to find out how retrofitting affects people’s health, indoor air quality, and whether it offers good value for money. The results will help guide future housing improvements to benefit both people and the environment. Who can participate? Residents living in selected social housing properties in Bradford may be invited to take part. Some homes will be retrofitted, and others will be used for comparison. What does the study involve? If you take part, we may install small sensors in your home to measure air quality, temperature, and humidity. You’ll be asked to complete short surveys about your health, comfort, and energy use at three different times. In some homes, we’ll also measure mould and how windows are used for ventilation. A small number of residents will be invited to take part in interviews to share their experiences. What are the possible benefits and risks of participating? Taking part could help improve understanding of how to make homes healthier and more comfortable. It may also help shape future housing policies. There are no major risks, but some people may find the surveys or sensors slightly inconvenient. All information will be kept private and secure. Where is the study run from? Bradford Teaching Hospitals NHS Foundation Trust in partnership with a major social housing provider (UK) When is the study starting and how long is it expected to run for? July 2025 to December 2029 Who is funding the study? National Institute for Health and Care Research (NIHR) (UK). Who is the main contact? Dagmar.Waiblinger@bthft.nhs.uk Temperature measured via the AirGradient sensor in 5-minute periods continuously from baseline until monitoring ends in Spring 2027 1. Indoor air quality (PM2.5, CO2, NO2, relative humidity) measured via the AirGradient sensor in 5-minute periods continuously from baseline until monitoring ends in Spring 2027 2. Energy use measured via energy meter readings at four time periods: the start and end of winter 2025/2026 and start and end of winter 2026/2027 3. Mould concentrations measured via a mould sensor in winter 2025/2026 and winter 2026/2027 (in a subset of homes) 4. Resident thermal comfort and satisfaction measured via questionnaire in winter 2025/2026 and in winter 2026/2027 5. Resident self-reported respiratory and mental health via questionnaire in winter 2025/2026 and in winter 2026/2027 Ethics approval required Yorkshire & The Humber - Bradford Leeds Research Ethics Committee

NHSBT Newcastle Blood Donor Centre, Holland Drive

Newcastle-upon-Tyne United Kingdom NE2 4NQ 25/YH/0081 10.1186/ISRCTN32222362 347237 CPMS: 64093, NIHR: 165582 347237 64093 165582 Observational cohort study Observational Cohort study Quality of life 2029-12-31T00:00:00.000Z United Kingdom England Bradford Teaching Hospitals NHS Foundation Trust

Bradford Royal Infirmary Duckworth Lane

Bradford England BD9 6RJ RAE@2.16.840.1.113883.2.1.3.2.4.18.48 Patient WP1 1. Homes managed by Incommunities, with energy performance certificate EPC) rating less than ‘C’ and identified for retrofitting 2. Eligible homes will have retrofitting scheduled from March to October 2026 (intervention) Or after March 2027 (Control group). Ideally the control homes are a close match to the intervention homes in building age, type, and EPC 3. Residents of eligible home able to give informed consent and are 18 years or over WP4 Interviews with resident 1. Participants who consented to WP1 and whose household is part of the intervention group 2. After a participant of such a household consented, other residents with minimum age 18 years of the same household will become also eligible , if they are able to give informed consent Non-resident Stakeholder interviews 1. Participants over the minimum aged of 18 years and have consented to be interviewed 2. Participants involved in social housing and delivering good indoor air quality Peer Researchers 1. Participants over the age of 18 years and consented to be part of study 2. Participants who belong to the same community where the research is taking place 3. Able to speak English well (additional languages welcomed) Mixed 18 Years 99 Years All 430 0 WP1 1. Households which are not scheduled for retrofitting according to the required timeline 2. Language barrier that can not be overcome with support of bilingual research assistants 3. Lack capacity for informed consent WP4 Resident Interviews 1. Households which are not scheduled for retrofitting according to the required timeline 2. Lack capacity for informed consent 3. Language barrier that can not be overcome with support of bilingual research assistants Non-resident stakeholder interviews 1. Not involved in social housing or air quality 2. Lack capacity for informed consent 3. Language barrier that can not be overcome with support of bilingual research assistants Peer researchers 1. Lack capacity for informed consent 2. Unable to speak English well 2025-07-15T00:00:00.000Z 2026-01-31T00:00:00.000Z Public Health, Persons with potential health hazards related to socioeconomic and psychosocial circumstances Other The Healthy Homes project is structured into four work packages (WPs) with both quantitative (WP1, WP2, WP3A + 3B) and qualitative (WP4) methods. WP1 and WP4 will require engagement with the public, recruitment/taking consent and data collection whilst WP2 will carry out secondary data analysis on the Connected Bradford dataset. WP3A utilises data collected as part of WP1 in order to model the changes in indoor conditions and energy/carbon exposures for a range of housing archetypes. WP3B is a health economic evaluation which utilises findings from WP3A to model the longer-term economic, productivity, and health impacts. Therefore, the methodology in the following will focus on WP1 and WP4. WP1: Residents of homes of interest will be made aware that they are eligible to take part in the study, information will be sent through Incommunities or directly to the household and raising awareness and engagement within the community. Potential participants will be able to express their interest through various channels: either by phone, email, online, post, face to face and will provide their contact details. Potential participants that have previously consented to be part of one of our Born in Bradford cohorts and are identified as living at an eligible address, can be contacted directly (phone or letter) as they have consented to contact for further studies. The Healthy Home team will contact interested residents and discuss their participation and ensure that they have access to the participant information sheet. A home visit will be arranged with residents who would like to take part at a convenient date and time. At the first study visit: The fieldworker will complete the consent form with the resident in the household that will complete the baseline questionnaire (Survey 1) and subsequent questionnaires. The baseline questionnaire will be completed as part of the visit. An air pollution sensor (AirGradient) will be installed in the main living area ensuring that the sensor's own internet connection is working. Ideally, monitoring will continue until the sensor is picked up 18 to 21 months later in March 2027 (from set up in the 3rd quarter of 2025). Participants will receive monthly vouchers (£20) each month of the monitoring period. The participant will receive a contact schedule considering his/her contact preferences. Subsequent questionnaires: Participants will receive three additional questionnaires to complete, roughly each about 6 months apart, covering the Winter 2025/26 (Survey 2), Summer 2026 (Survey 3) and Winter 2026/2027 (Survey 4) periods. Questionnaires will be deployed according to participant preferences as an online link via email, in paper form, over the phone or as part of a home visit. Energy meter readings: We will collect energy meter readings before and after each winter period (e.g. 4 measurements in total). As much as possible we will tie these readings in with existing scheduled contacts. We give participants the option to take the reading themselves or to be taken by the fieldworker. Additional measurements (sub-sample): Mould sensor measurement: we may ask a smaller number of participants at the first visit whether they would agree to mould measurements at different time points. We will confirm with the participant each time that they are still happy with a repeat measurement. Measuring ventilation: we may ask participants whether they would be happy to accommodate window sensors on the windows in the living room for periods of time, for example in the winter. We will provide further information before any deployment and confirm that the participant is happy to have these installed. We aim for that visits for installation or de-installation to coincide with scheduled contacts, for example, subsequent questionnaires, mould sensor measurements and/or delivery of voucher. WP4: Interviews Participants of the intervention group will be asked at the first visit whether they would be happy to receive information about interviews carried out as part of WP4. Interested participants will receive further participant information in the winter period following recruitment. Up to 20 participants will become part of this sample and will sign a separate consent form prior to the interview. The interview will be conducted by a researcher using an interview guide and will take place at the participants home, or online, according to participant preferences. A further interview will take place one year later after the retrofitting has taken place. Participants will receive a £20 voucher for each interview. 10 non-resident stakeholders will also be interviewed. These will be those involved in social housing and delivering good indoor air quality and will be recruited through key contacts and snowball sampling. They will sign a separate consent form. The interviews will be conducted by a researcher of the Healthy Homes team using a different interview guide at a community venue, or online. These interviews will take place at two points, these are planned for Summer 2026 and Spring 2028. WP4-Peer Research 10 Peer-researchers will be recruited by one or two community organisations. If they wish to be part of the study, they will sign a consent form. They will then undertake some training and work with the research team to design a study (this in unknown at present but could include photographs, questionnaires, mapping, audio recordings, workshops). Each peer researcher will collect data from 10 residents, in phase 1 and 10 residents in phase 2 (12-18 months later). We will provide the ethics committee with further details of these activities as part of an amendment, prior to this element of the work starting. Other Quantitative data collected in this study will be available as part of the Born in Bradford repository. Data will be cleaned prior to availability. All data collected have been granted ethical approval and participant consent for its continued availability. Data requests are made to the BiB executive using the form available from the study website: http://www.borninbradford.nhs.uk (please click on ‘Our Data’ and ‘How to Access Data’ to access the form and guidance). All requests are carefully considered and accepted where possible. Available on request Stored in publicly available repository

Study website Migrated from study website field

6e32c2bd-c636-4ee9-8548-dca3df3e20d5 63628c2a-3cf6-4af0-902c-9566949ee5f4 95db7c97-a598-4913-a25e-ce5e302cd931 46e9a8bd-8da3-402f-82ac-e727237af2e3 95acc0cd-42e8-4bc9-8957-9e61287c96e5 Yes Participant information sheet 47626 2-WP1-Healthy-Homes-PIS_-V2.0_12052025.pdf e0ab1229-5bc3-402d-b9aa-1ae96d9cfa70 true application/pdf 150326 62955e3bad6f622f7408bf3506be1a05 Dagmar Waiblinger Public Scientific Principal investigator

Bradford Institute for Health Research, Bradford Royal Infirmary Temple Bank House, Duckworth Lane

Bradford United Kingdom BD9 6RJ +44 1274383317 Dagmar.Waiblinger@bthft.nhs.uk Public Tiffany Yang https://orcid.org/0000-0003-4549-7850 Public Scientific Principal investigator

Bradford Institute for Health Bradford Royal Infirmary

Bradford United Kingdom BD9 6RJ - Tiffany.Yang@bthft.nhs.uk Public Ella Foggitt Public

Bradford Institute for Health Bradford Royal Infirmary

Bradford United Kingdom BD9 6RJ - Ella.Foggitt@bthft.nhs.uk Public Bradford Teaching Hospitals NHS Foundation Trust Hospital/treatment centre https://ror.org/05gekvn04 Non-commercial NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC) 11440256 true Improving quality of life and behaviour that challenges in people with mild to moderate intellectual disability through person-centred solution focused communication (ICONIC) ICONIC Current study objectives as of 16/04/2026: 1. To pilot the adapted DIALOG quality of life scale and intervention (aDIALOG+) and obtain feedback on what aspects of the intervention (including the aDIALOG scale, supporting app, training and manual) worked well or did not work well and suggestions for improvement. 2. To test the psychometric properties of the aDIALOG scale to establish whether the aDIALOG scale is a useful quality of life measure in people with learning disability, and to compare it with the original DIALOG scale in people with mental health issues. 3. To conduct a feasibility study of aDIALOG+ delivered by clinicians from community learning disability services to assess recruitment and retention of service users and clinicians. 4. To conduct a feasibility study of aDIALOG+ delivered by care workers from care homes (supported living or residential care) for people with learning disability to assess recruitment and retention of care homes, care workers and service users. _____ Previous study objectives: 1. To pilot the adapted DIALOG quality of life scale and intervention (aDIALOG+) and obtain feedback on what aspects of the intervention (including the aDIALOG scale, supporting app, training and manual) worked well or did not work well and suggestions for improvement. 2. To test the psychometric properties of the aDIALOG scale to establish whether the aDIALOG scale is a useful quality of life measure in people with learning disability. 3. To conduct a feasibility study of aDIALOG+ delivered by clinicians from community learning disability services to assess recruitment and retention of service users and clinicians. 4. To conduct a feasibility study of aDIALOG+ delivered by care workers from care homes (supported living or residential care) for people with learning disability to assess recruitment and retention of care homes, care workers and service users. Background and study aims This research is part of the ICONIC programme, which aims to improve quality of life and behaviour that challenges in people with mild to moderate learning disability through person-centred solution focused communication. DIALOG+ is an evidence based, face-to-face intervention delivered by health professionals using a tablet, which structures routine care sessions to ensure that care planning is personalised, holistic and co-produced. DIALOG+ involves collaboratively completing a quality-of-life scale and then using those ratings to have a solution focused discussion in order to set actions and improve service user satisfaction. Studies have found that it can enhance the communication between service users and those who support them, and can improve quality of life in people with mental health problems, but it has not been used in people with learning disabilities. We want to make DIALOG+ accessible and suitable for people with learning disability and to use it to help individuals think about things in their life they want to improve (e.g. leisure activities, accommodation) by using resources available to them or their carers. Our aim is to test if it improves quality of life and behaviour. Who can participate? Piloting Study: Service users will be eligible to take part if they are aged 18 or over, have mild or moderate learning disability based on service records/clinical notes, have a current history of behaviour that challenges (at least one incident of self-injurious behaviour, physical or verbal aggression, anger / frustration outbursts, or damage to property in the last 3 months), are living in any setting including the family home and supported living/ residential home, and can provide informed verbal or written consent. Psychometric Testing Study: Service users will be eligible to take part if they are aged 18 or over, have mild or moderate learning disability based on service records / clinical notes, are known to community ID services from participating NHS trusts or to voluntary groups for people with ID, and can provide informed verbal or written consent. Comparison Testing Study: Service users will be eligible to take part if they are aged between 18 and 65 years, are under the care of a community psychiatric team or currently an inpatient in a psychiatric hospital in East London NHS Foundation Trust, have a primary diagnosis of a mental health issue, and can provide informed verbal or written consent. Clinical Services Feasibility Study: Service users will be eligible to take part if they are aged 18 or over, have mild or moderate learning disability based on service records / clinical notes, have a current history of behaviour that challenges (at least one incident of self-injurious behaviour, physical or verbal aggression, anger / frustration outbursts, or damage to property in the last 3 months), are living in any setting including the family home and supported living/ residential home, and can provide informed verbal or written consent. Care Homes Feasibility Study: Service users will be eligible to take part if they are aged 18 or over, have mild or moderate learning disability based on service records / clinical notes, have a current history of behaviour that challenges (at least one incident of self-injurious behaviour, physical or verbal aggression, anger / frustration outbursts, or damage to property in the last 3 months), are residing in supported living or residential care, and can provide informed verbal or written consent. What does the study involve? Comparison Testing Study: A resident trainee, clinical studies officer or a member of the research team will arrange a face-to-face or remote (via Teams or Zoom) meeting with at least 200 service users with any mental health diagnosis (without learning disability) to complete the aDIALOG scale, along with the original DIALOG scale, and some demographic questions (e.g. gender, age, ethnicity, primary mental health diagnosis, how they receive their care and the number of years of treatment). Alternatively, service users can be sent the consent form and questionnaires to complete via email or post. Clinical Services Feasibility Study: In this study, we will be assessing whether it is feasible for clinicians to deliver an adapted version of aDIALOG+ to service users with mild or moderate learning disability who have behaviours that challenge (such as physical or verbal aggression towards others or property, anger / frustration outbursts, and self-injurious behaviour). Our aim is to establish whether it is possible to recruit 8-12 clinicians, 30 service users and 30 participant carers (if applicable) into the study. We will also examine the number of sessions of aDIALOG+ that are delivered over 6 months, the quality of the sessions, and the experiences and views of clinicians, service users and participant carers about the intervention, what worked well and what needs to be improved. We will also examine if there are any potential benefits of the intervention by looking at changes in outcome measures such as behaviour, community participation, quality of life and service use. Care Homes Feasibility Study: In this study, we will be assessing whether it is feasible for care workers to deliver an adapted version of DIALOG+ (aDIALOG+) to service users with mild or moderate learning disability who have behaviours that challenge (such as physical or verbal aggression towards others or property, anger / frustration outbursts, and self-injurious behaviour). What are the possible benefits and risks of participating? For the piloting study, service users and care workers will receive a £20 shopping voucher for participating in the interview/focus group following the 6-week intervention period to thank them for their time, and service users will also receive a £20 voucher after taking part in the psychometric testing study. For the psychometric comparison study service users will receive a £10 voucher for taking part. For the clinical services and care homes feasibility studies, service users, participant carers and care workers will receive a £20 shopping voucher for completing qualitative interviews, and service users will receive £20 after completing the baseline assessment and £20 prior to the 6-month follow-up assessments to thank them for their time. Participant carers and care workers will also receive £20 following completion of the baseline assessment and prior to the 6-month follow-up assessments. By sharing experience and views on the aDIALOG+ software, it will help us to improve it and adapt it for clinicians and care workers who use aDIALOG+ in the future. We know that using the original DIALOG+ intervention improved the quality of life of people with psychosis when they used it face to face and we are hoping we can replicate those benefits in service users with learning disability. Where is the study run from? The research is coordinated at the Unit for Adult Mental Health and Wellbeing, Queen Mary University of London. Dr Afia Ali has overall responsibility for the study and it is sponsored by East London NHS Foundation Trust. When is the study starting and how long is it expected to run for? The piloting study started in January 2026 and is expected to run for 3 months. The psychometric testing study started in July 2025 and is expected to run for 17 months. The comparison testing study started in May 2026 and is expected to run for 12 months. The clinical services and care homes feasibility studies started in May 2026 and are expected to run for 13 months. Who is funding the study? National Institute for Health and Care Research (NIHR) (UK). Who is the main contact? Dr Afia Ali (Chief Investigator) afia.ali@qmul.ac.uk / afia.ali6@nhs.net Miss Laura Miller (Programme Manager) l.miller@qmul.ac.uk / laura.miller58@nhs.net Current primary outcomes as of 16/04/2026: WP1a Piloting: 1. Acceptability of / feedback on the intervention is measured using semi-structured interviews / focus groups after 2-4 weeks. 2. Intervention implementation processes from the perspective of clinicians and care workers are assessed using the NoMAD questionnaire after 2-4 weeks. WP1b Psychometric Testing: 1. Construct and concurrent validity of the aDIALOG scale are measured using the Mini-MANS LD and the WHOQOL Disabilities module and Clinical Outcome in Routine Evaluation- Learning Disability (CORE-LD), 14 item version (measure of psychological distress) at baseline. 2. Test re-test reliability of the aDIALOG scale is measured by completing the scale at baseline and again 24 hours to 1 week later. WP1b Comparison Testing: 1. Reliability of the aDIALOG scale through measuring the internal consistency and comparing to the original DIALOG scale. 2. Validity of the aDIALOG scale measured using evenness of distribution of scores compared to the original DIALOG scale and confirmatory factor analysis. _____ Previous primary outcomes: WP1a Piloting: 1. Acceptability of / feedback on the intervention is measured using semi-structured interviews / focus groups with at 6 weeks. 2. Intervention implementation processes from the perspective of clinicians and care workers are assessed using the NoMAD questionnaire at 6 weeks. WP1b Psychometric Testing: 1. Construct and concurrent validity of the aDIALOG scale are measured using the Mini-MANS LD and the WHOQOL Disabilities module and Clinical Outcome in Routine Evaluation- Learning Disability (CORE-LD), 14 item version (measure of psychological distress) at baseline. 2. Test re-test reliability of the aDIALOG scale is measured by completing the scale at baseline and again 24 hours to 1 week later. Feasibility studies: 1. Changes in behaviour in service users is measured using the Aberrant Behaviour Checklist (ABC) – Irritability subscale at baseline and 6 months Feasibility studies: 1. Quality of life in service users is measured using the 13- item WHOQOL Disabilities module (WHOQOL-DIS) at baseline and 6 months 2. Community and Leisure participation in service users is measured using the Guernsey Community Participation and Leisure Assessment – Revised (GCPLA-R) at baseline and 6 months 3. Changes in psychological distress in service users is measured using the Learning Disability – Clinical Outcomes in Routine Evaluation, 14 item version (LD-CORE-14) at baseline and 6 months 4. Changes in the presence of psychiatric disorders in service users is measured using the Moss Psychiatric Assessment Schedule - Check (Moss-PAS Check) at baseline and 6 months 5. Changes in behaviour and functioning in service users as a result of the intervention is measured using a modified version of the Clinical Global Impressions Scale – Improvement version (CGI-I) at 6 months 6. Paid and family carer distress in participant carers is measured using the Kessler Psychological Distress Scale - K6 at baseline and 6 months 7. Changes in health-related quality of life in service users is measured using the EuroQol Five Dimensions - Learning Disability modified version of the EQ-5D-3L at baseline and 6 months. A proxy version of the EQ-5D-5L will also be completed by participant carers at baseline and 6 months. 8. Health related quality of life in participant carers is measured using the EQ-5D-5L at baseline and 6 months. 9. Health and social care contacts and medication in service users is measured using a modified version of the Client Services Receipt Inventory (CSRI) at baseline and 6 months. 10. Treatment costs of delivering the intervention are measured using staff time, room bookings and other resource use in participating clinical services and care homes. 11. Intervention implementation processes from the perspective of clinicians and care workers are assessed using the NoMAD questionnaire at 6 months. 12. Recruitment is measured using screening logs of the number of clinicians, care workers and eligible service users who were approached agreed to take part throughout the study at 6 months. 13. Retention is measured using withdrawal forms completed to record clinicians, care workers and service users who drop out of the study and the reasons why, as well as the number of participants that complete the follow-up assessment at 6 months. 14. Intervention adherence is measured using session completion data from the aDIALOG+ app at 6 months. 15. Intervention fidelity is measured using audio/video recordings of sessions, action plans from the aDIALOG+ app and completed session fidelity checklists at 6 months. 16. Acceptability of the intervention is measured using semi-structured interviews / focus groups with at 6 months. Ethics approval required South West - Cornwall & Plymouth Research Ethics Committee

2 Redman Place, Stratford

London United Kingdom E20 1JQ 25/SW/0055 10.1186/ISRCTN11440256 349711 CPMS: 68145, NIHR: 205440 349711 68145 205440 Interventional non-randomized Interventional Non randomised study Treatment 2027-06-01T00:00:00.000Z United Kingdom England East London NHS Foundation Trust

Robert Dolan House 9 Alie Street

London England E1 8DE RWK@2.16.840.1.113883.2.1.3.2.4.18.48 Cornwall Partnership NHS Foundation Trust

Carew House Beacon Technology Park Dunmere Road

Bodmin England PL31 2QN RJ8@2.16.840.1.113883.2.1.3.2.4.18.48 North London NHS Foundation Trust

Camden Learning Disability Service 5 Pancras Square

London England N1C 4AG Cambridgeshire and Peterborough NHS Foundation Trust

Elizabeth House Fulbourn Hospital Fulbourn

Cambridge England CB21 5EF RT1@2.16.840.1.113883.2.1.3.2.4.18.48 Derbyshire Healthcare NHS Foundation Trust

Trust Headquarters Kingsway Hospital Kingsway

Derby England DE22 3LZ RXM@2.16.840.1.113883.2.1.3.2.4.18.48 Hampshire and Isle of Wight Healthcare NHS Foundation Trust

Tatchbury Mount Hospital Calmore

Southampton England SO40 2RZ RW1@2.16.840.1.113883.2.1.3.2.4.18.48 Rotherham Doncaster and South Humber NHS Foundation Trust

Woodfield House Tickhill Road

Doncaster England DN4 8QN RXE@2.16.840.1.113883.2.1.3.2.4.18.48 Livewell Southwest

Local Care Centre 200 Mount Gould Road

Plymouth England PL4 7PY NR501@2.16.840.1.113883.2.1.3.2.4.18.48 South West Yorkshire Partnership Teaching NHS Foundation Trust

Trust Headquarters Fieldhead Hospital Ouchthorpe Lane

Wakefield England WF1 3SP RXG@2.16.840.1.113883.2.1.3.2.4.18.48 Bradford District Care NHS Foundation Trust

New Mill Victoria Road Saltaire

Shipley England BD18 3LD TAD@2.16.840.1.113883.2.1.3.2.4.18.48 Norfolk Community Health and Care NHS Trust

Research Office, Ground Floor, West Pottergate Medical Centre, Earlham Road

Norwich England NR2 4BX Dane View Care Home with Nursing

165 Glenfield Road

Leicester England LE3 6DP VNC2X@2.16.840.1.113883.2.1.3.2.4.18.48 Central and North West London NHS Foundation Trust

Northwick Park Hospital, Mental Health Unit, Watford Road

Harrow England HA1 3UJ Patient Current key inclusion criteria as of 01/09/2026: WP1a: Service Users Inclusion Criteria: 1. Aged 18 years or over 2. Mild or moderate ID based on service records / clinical notes 3. Current history of behaviour that challenges (at least one incident of self-injurious behaviour, physical or verbal aggression, anger / frustration outbursts, or damage to property in the last 3 months) 4. Living in any setting including the family home and supported living/residential home 5. Can provide informed verbal or written consent WP1b Psychometric Testing: Service Users Inclusion Criteria: 1. Aged 18 years or over 2. Mild or moderate ID based on service records / clinical notes 3. Are known to community ID services from participating NHS trusts or to voluntary groups for people with ID 4. Can provide informed verbal or written consent WP1b Comparison Testing: Service Users Inclusion Criteria: 1. Aged between 18 and 65 years 2. Under the care of a community psychiatric team or currently an inpatient in a psychiatric hospital in East London NHS Foundation Trust 3. Have a primary diagnosis of a mental health issue 4. Can provide informed verbal or written consent WP2: Service Users Inclusion Criteria: 1. Aged 18 years or over 2. Mild or moderate ID based on service records / clinical notes 3. Current history of behaviour that challenges (at least one incident of self-injurious behaviour, physical or verbal aggression, anger / frustration outbursts, or damage to property in the last 3 months) 4. Living in any setting including the family home and supported living/residential home 5. Can provide informed verbal or written consent WP3: Service Users Inclusion Criteria: 1. Aged 18 years or over 2. Mild or moderate ID based on service records / clinical notes 3. Current history of behaviour that challenges (at least one incident of self-injurious behaviour, physical or verbal aggression, anger / frustration outbursts, or damage to property in the last 3 months) 4. Residing in supported living or residential care 5. Can provide informed verbal or written consent WP1a Clinicians Inclusion Criteria: 1. Aged 18 or over 2. Currently working within a community ID service, intensive support team or in a local authority or social care organisation for people with ID 3. From any profession (e.g. psychology, nursing, speech and language therapy, psychiatry, social work), with a minimum of six months experience working with people with ID 4. Consent to participation WP2 Clinicians Inclusion Criteria: 1. Aged 18 or over 2. Currently working within a community ID service, intensive support team or in a local authority or social care organisation for people with ID 3. From any profession (e.g. psychology, nursing, speech and language therapy, psychiatry, social work), with a minimum of six months experience working with people with ID 4. Consent to participation WP3 Care Workers Inclusion Criteria: 1. Aged 18 or over 2. Have worked in the care home for at least three months 3. Provide at least one day of support per week to service users 4. Consent to participation _____ Previous inclusion criteria as of 16/04/2026: WP1a: Service Users Inclusion Criteria: 1. Aged 18 years or over 2. Mild or moderate ID based on service records / clinical notes 3. Current history of behaviour that challenges (at least one incident of self-injurious behaviour, physical or verbal aggression, temper tantrums / outbursts, or damage to property in the last 3 months) 4. Living in any setting including the family home and supported living/residential home 5. Can provide informed verbal or written consent WP1b Psychometric Testing: Service Users Inclusion Criteria: 1. Aged 18 years or over 2. Mild or moderate ID based on service records / clinical notes 3. Under community ID services from the East London Foundation Trust - Updated 04/11/2025: from participating NHS trusts 4. Can provide informed verbal or written consent WP1b Comparison Testing: Service Users Inclusion Criteria: 1. Aged between 18 and 65 years 2. Living in the community and treated as out-patients by community psychiatric teams from participating NHS trusts 3. Have a primary diagnosis of a mental health issue 4. Can provide informed verbal or written consent WP2: Service Users Inclusion Criteria: 1. Aged 18 years or over 2. Mild or moderate ID based on service records / clinical notes 3. Current history of behaviour that challenges (at least one incident of self-injurious behaviour, physical or verbal aggression, temper tantrums / outbursts, or damage to property in the last 3 months) 4. Living in any setting including the family home and supported living/residential home 5. Can provide informed verbal or written consent WP3: Service Users Inclusion Criteria: 1. Aged 18 years or over 2. Mild or moderate ID based on service records / clinical notes 3. Current history of behaviour that challenges (at least one incident of self-injurious behaviour, physical or verbal aggression, temper tantrums / outbursts, or damage to property in the last 3 months) 4. Residing in supported living or residential care 5. Can provide informed verbal or written consent _____ Previous inclusion criteria: WP1a 1. Service Users Inclusion Criteria: 1. Aged 18 or over 2. Mild or moderate ID based on service records / clinical notes 3. Current history of behaviour that challenges (at least one incident of self-injurious behaviour, physical aggression or damage to property in the last 3 months) 4. Living in any setting including the family home and supported living/residential home 5. Can provide informed verbal or written consent 2. Clinicians Inclusion Criteria: 1. Aged 18 or over 2. Currently working within a community ID service, intensive support team or in a local authority or social care organisation for people with ID 3. From any profession (e.g. psychology, nursing, speech and language therapy, psychiatry, social work), grade 4 and above with a minimum of six months experience working with people with ID 4. Consent to participation 3. Care Workers Inclusion Criteria: 1. Aged 18 or over 2. Have worked in the care home for at least three months 3. Provide at least one day of support per week to service users 4. Consent to participation WP1b 1. Service Users Inclusion Criteria: 1. Aged 18 or over 2. Mild or moderate ID based on service records / clinical notes 3. Under community ID services from the East London Foundation Trust - Updated 04/11/2025: from participating NHS trusts 4. Can provide informed verbal or written consent WP2 1. Service Users Inclusion Criteria: 1. Aged 18 or over 2. Mild or moderate ID based on service records / clinical notes 3. Current history of behaviour that challenges (at least one incident of self-injurious behaviour, physical aggression or damage to property in the last 3 months) 4. Living in any setting including the family home and supported living/residential home 5. Can provide informed verbal or written consent 2. Clinicians Inclusion Criteria: 1. Aged 18 or over 2. Currently working within a community ID service, intensive support team or in a local authority or social care organisation for people with ID 3. From any profession (e.g. psychology, nursing, speech and language therapy, psychiatry, social work), grade 4 and above with a minimum of six months experience working with people with ID 4. Consent to participation 5. Have not participated in other work packages 3. Participant Carers Inclusion Criteria: 1. Aged 18 or over 2. Are paid or unpaid (e.g. family carer); if a paid carer, need to have worked with the person for at least six months and should know the person well and support the person on a regular basis 3. Consent to participation WP3 1. Service Users Inclusion Criteria: 1. Aged 18 or over 2. Mild or moderate ID based on service records / clinical notes 3. Current history of behaviour that challenges (at least one incident of self-injurious behaviour, physical aggression or damage to property in the last 3 months) 4. Residing in supported living or residential care 5. Can provide informed verbal or written consent 2. Care Homes Inclusion Criteria: 1. Supported living or residential placements for service users with ID in the participating areas 2. Service manager has agreed for the care home to take part 3. Care Workers Inclusion Criteria: 1. Aged 18 or over 2. Have worked in the care home for at least three months 3. Provide at least one day of support per week to service users 4. Consent to participation 5. Have not participated in other work packages Mixed 18 Years 100 Years All 502 472 Current key exclusion criteria as of 01/09/2026: WP1a Clinicians Exclusion Criteria: 1. Under 18 years of age 2. Not currently working within a community ID service, intensive support team or in a local authority or social care organisation for people with ID 3. Less than 6 months experience working with people with ID 4. Do not consent to participation WP1b Psychometric Testing: Service Users Exclusion Criteria: 1. Under 18 years of age 2. Severe ID based on service records/clinical notes 3. Not known to community ID services from participating NHS trusts or to voluntary groups for people with ID 4. Unable to provide informed verbal or written consent WP1b Comparison Testing: 1. Under 18 years of age and over 66 years of age 2. Do not have a primary mental health diagnosis (e.g., substance misuse disorder) 3. Unable to provide informed verbal or written consent WP2 Clinicians Exclusion Criteria: 1. Under 18 years of age 2. Not currently working within a community ID service, intensive support team or in a local authority or social care organisation for people with ID 3. Less than 6 months experience working with people with ID 4. Do not consent to participation WP3 Care Workers Exclusion Criteria: 1. Under 18 years of age 2. Have worked in the care home for less than 3 months 3. Do not provide at least one day of support per week to service users 4. Do not consent to participation _____ Previous exclusion criteria as of 16/04/2026: WP1b Psychometric Testing: Service Users Exclusion Criteria: 1. Under 18 years of age 2. Severe ID based on service records/clinical notes 3. Not under community ID services from the East London Foundation Trust - Updated 04/11/2025: from participating NHS trusts 4. Unable to provide informed verbal or written consent WP1b Comparison Testing: 1. Under 18 years of age and over 66 years of age 2. Currently in an inpatient in a psychiatric hospital 3. Do not have a primary mental health diagnosis (e.g., substance misuse disorder) 4. Unable to provide informed verbal or written consent _____ Previous exclusion criteria: WP1a 1. Service Users Exclusion Criteria: 1. Under 18 years of age 2. Severe ID based on service records / clinical notes 3. Likely to move out of borough within the next 3 months or at imminent risk of hospital admission 4. Unable to provide informed verbal or written consent 2. Clinicians Exclusion Criteria: 1. Under 18 years of age 2. Not currently working within a community ID service, intensive support team or in a local authority or social care organisation for people with ID 3. Below grade 4 and less than 6 months experience working with people with ID 4. Do not consent to participation 3. Care Workers Exclusion Criteria: 1. Under 18 years of age 2. Have worked in the care home for less than 3 months 3. Do not provide at least one day of support per week to service users 4. Do not consent to participation WP1b 1. Service Users Exclusion Criteria: 1. Under 18 years of age 2. Severe ID based on service records / clinical notes 3. Not under community ID services from the East London Foundation Trust - Updated 04/11/2025: from participating NHS trusts 4. Unable to provide informed verbal or written consent WP2 1. Service Users Exclusion Criteria: 1. Under 18 years of age 2. Severe ID based on service records / clinical notes 3. Already participating in WP3 or involved in another clinical trial 4. Likely to move out of borough within the next 6 months or at imminent risk of hospital admission 5. Unable to provide informed verbal or written consent 2. Clinicians Exclusion Criteria: 1. Under 18 years of age 2. Not currently working within a community ID service, intensive support team or in a local authority or social care organisation for people with ID 3. Below grade 4 and less than 6 months experience working with people with ID 4. Do not consent to participation 5. Have participated in other work packages 3. Participant Carers Exclusion Criteria: 1. Under 18 years of age 2. If a paid carer and have worked with the person for less than six months and/or do not know the person well and/or support the person on a regular basis 3. Do not consent to participation WP3 1. Service Users Exclusion Criteria: 1. Under 18 years of age 2. Severe ID based on service records / clinical notes 3. Already participating in WP2 or involved in another clinical trial 4. Likely to move out of the care home within the next six months or are at imminent risk of hospital admission 5. Unable to provide informed verbal or written consent 2. Care Homes Exclusion Criteria: 1. Not supported living or residential placements for service users with ID and/or not in the participating areas 2. Service manager does not agree for the care home to take part 3. Care Workers Exclusion Criteria: 1. Under 18 years of age 2. Have worked in the care home for less than 3 months 3. Do not provide at least one day of support per week to service users 4. Do not consent to participation 5. Have participated in other work packages 2025-08-07T00:00:00.000Z 2026-11-30T00:00:00.000Z Mild to moderate intellectual disability Mental and Behavioural Disorders Current interventions as of 16/04/2026: An adapted version of DIALOG+ (a brief, low-cost solution-focused intervention that improves the therapeutic effectiveness of routine clinical meetings between patients and clinicians) for individuals with learning disability will be piloted for 2-4 weeks, the adapted scale tested for psychometric properties at 2 timepoints (within 24 hours-1 week) and comparison tested with the original DIALOG scale, and delivered in clinical and care home feasibility studies for 6 months. _____ Previous interventions: An adapted version of DIALOG+ (a brief, low-cost solution-focused intervention that improves the therapeutic effectiveness of routine clinical meetings between patients and clinicians) for individuals with learning disability will be piloted for 4-6 weeks, tested for psychometric properties at 2 timepoints (within 24 hours-1 week), and delivered in clinical and care home feasibility studies for 6 months. Behavioural Data sharing statement to be made available at a later date Protocol

086586ae-3919-40ae-b565-48eaf7fd7840 5bfd6e0a-f6be-42db-af32-79e65800296e 174d80bc-3550-48b2-8785-521553bef35e bd3c8ad4-709e-4148-8736-f221f3b481aa No Protocol file 47564 ICONIC_ WP1 2 and 3 Protocol v1.0 30.05.2025.pdf 6003dfb0-844c-4af6-a553-045bcb24459d true application/pdf 651827 4568e0d65fbd906a796445e923b512a4 Protocol file ISRCTN11440256_PROTOCOL_V3.0_14Oct2025.pdf 7969177c-3c73-44d2-8686-e72b1ec0a78e true application/pdf 746942 3152c1ad486bbc76c7d41a04e951bc25 Protocol file ISRCTN11440256_WP1 2 and 3_PROTOCOL_V5.0_02Apr2026.pdf 4f2b9443-e9af-4f49-9086-51d2b8b13c3d true application/pdf 784320 096cbe3095124bcd27c3728b1f59aa94 Protocol file ISRCTN11440256 ICONIC_WP1 2 and 3 protocol v7.0 07.08.2026.pdf f4e82e02-6c9d-4771-b8bb-e7ce9f38ac7b true application/pdf 679559 508e1db2b92f3a1d7372b6369bbd9c49 Protocol file ISRCTN11440256_PROTOCOL_V8.0_16Sep2026.pdf e806e700-96ca-4eec-b82d-e3047e0cc8a3 true application/pdf 785067 5b5323785ca6ea45878d669d18fae9a0 Laura Miller https://orcid.org/0000-0001-8802-3554 Public Scientific

Unit for Adult Mental Health and Wellbeing Centre for Psychiatry and Mental Health (CPMH) Wolfson Institute of Population Health Queen Mary University of London Yvonne Carter Building, 58 Turner Street

London United Kingdom E1 2AB +44 7352 980401 l.miller@qmul.ac.uk Public Afia Ali https://orcid.org/0000-0002-0104-9370 Principal investigator

Unit for Adult Mental Health and Wellbeing Centre for Psychiatry and Mental Health (CPMH) Wolfson Institute of Population Health Queen Mary University of London Yvonne Carter Building, 58 Turner Street

London United Kingdom E1 2AB +44 7836 584017 afia.ali@qmul.ac.uk Public North East London NHS Foundation Trust Hospital/treatment centre https://ror.org/023e5m798 Non-commercial NIHR Central Commissioning Facility (CCF) 92742608 true The ROSIER trial: requirement for surgical intervention after endoscopic retrograde cholangiopancreatography ROSIER Following endoscopic retrograde cholangiopancreatography (ERCP), treatment with expectant management (managed with the intention of not undergoing cholecystectomy) is non-inferior to laparoscopic cholecystectomy in patients with common bile duct stones. Background and study aims This study aims to improve treatment for patients after gallstones (common bile duct stones). We want to find out if patients benefit from having their gallbladder removed after gallstone treatment. Gallstones are solid deposits that form in the gallbladder. When these stones move into the bile duct, they can cause pain and lead to complications, often needing urgent medical treatment. Each year, around 20,000 endoscopic retrograde cholangiopancreatography (ERCP) procedures are performed in England to remove these stones. After ERCP, patients are usually advised to talk to a surgeon about the possible removal of their gallbladder to prevent future complications from gallstones. Although the National Institute for Health and Care Excellence (NICE) recommends this surgery, practice varies a lot, and nearly half of patients who are eligible for surgery don’t have an operation. This inconsistency means that around half of the patients could either be under- or over-treated. We need more evidence to confirm which approach is best for patients. Who can participate? Adult patients aged 18 years and over who have recently had bile duct stones cleared from their bile duct and are considered fit for surgery. What does the study involve? Participants will be randomly assigned to one of two groups. Half of the participants will be in the surgery group and have an operation to remove their gallbladder. The other half will be in the expectant management group, who will not have a scheduled operation to remove their gallbladder. Instead, they will be monitored by their healthcare team (with no intention of undergoing gallbladder-removal surgery). All participants will be followed up for 2 years from when they enter the study. Clinical data will be collected about participants when they enter the study and then at 3, 6, 12 and 24 months afterwards. Participants will be asked to complete a set of quality of life questionnaires when they enter the study and then every three months for 2 years. In between the 3-monthly questionnaires, participants will also be asked to complete a short questionnaire each month about their pain. Some study data will be collected from Hospital Episode Statistics, a standard NHS registry. For randomly selected participants, copies of their scans and reports from the procedure they had done to remove their bile duct gallstones prior to study entry will be collected by the study team for central review purposes. Interviews will take place with some of the patients who were approached for the ROSIER study, to find out why they chose to take part in the study or not. Interviews will also be carried out with participating hospital staff to find out their views about the study and the study processes. What are the possible benefits and risks of participating? We don’t know if participants will personally benefit from taking part in this research, but it is possible. As the research involves treatments that participants could get in standard care, we don’t anticipate there being any extra risk to participants from taking part in the study. For participants who have gallbladder-removal surgery during their participation in the study, the operation would be performed as per local routine care. Therefore, the risks of undergoing this procedure would be the same both inside and outside of the study. Where is the study run from? The study is being run from the Clinical Trials Research Unit at the University of Leeds in the UK. When is the study starting and how long is it expected to run for? June 2024 to September 2030 Who is funding the study? The study is funded by the National Institute for Health and Care Research (NIHR) (UK) Who is the main contact? 1. Rachel Kelly (Senior Trial Coordinator), ROSIER@leeds.ac.uk 2. Mr Andrew Smith, andrewmsmith@nhs.net 3. Prof. Giles Toogood, giles.toogood@nhs.net Patient-reported pain, defined by the area under the curve (AUC) of the SF-36 bodily pain domain within 24 months of randomisation. This will be assessed monthly over the 24-month post-randomisation period. 1. Overall patient wellbeing measured using the condition-specific Otago Gallstones Condition Specific Questionnaire (CSQ) every 3 months up to 24 months post-randomisation 2. SF-36 physical functioning, physical role limitations, general health perceptions, energy/vitality, social functioning, emotional, and mental health domains, assessed every 3 months for up to 24 months post-randomisation 3. Adverse events occurring within 24 months post-randomisation 4. Subsequent disease or intervention-related surgeries occurring within 24 months post-randomisation 5. Number and timing of readmissions (for biliary events, complications and treatment) occurring within 24 months of randomisation, derived from Hospital Episode Statistics (HES) data 6. Cost-utility as measured by the EQ-5D-5L and health care resource use questionnaires assessed every 3 months up to 24 months post-randomisation 7. All-cause mortality within 24 months post-randomisation Exploratory outcome measure: Identifying potential risk factors that may predict the need for laparoscopic cholecystectomy within 24 months of randomisation to expectant management. Potential risk factors that may be explored will include, but are not necessarily limited to, age, sex, BMI, cholangitis, obstructive jaundice without sepsis, pancreatitis, biliary pain or colic, cholecystitis, previous abdominal surgery, bile duct related factors (stone size, number of stones, duct size, obstruction in Hartmann’s pouch), and gallbladder wall thickness on ultrasound. Full details of risk factors to be explored will be detailed a priori in the statistical analysis plan. Old ethics approval format Approved 13/03/2025, London - Bloomsbury Research Ethics Committee (Health Research Authority, 2 Redman Place, Stratford, London, E20 1JQ, UK; +44 (0)207 104 8384, +44 (0)207 104 8256, +44 (0)207 104 8276; bloomsbury.rec@hra.nhs.uk), ref: 25/LO/0110 10.1186/ISRCTN92742608 333432 CPMS: 58170, NIHR: 159585 333432 58170 159585 Randomized; Interventional; Design type: Treatment, Surgery, Active Monitoring Interventional Randomised controlled trial Treatment 2030-09-30T00:00:00.000Z United Kingdom England Leeds Teaching Hospitals NHS Trust

St. James's University Hospital Beckett Street

Leeds England LS9 7TF RR8@2.16.840.1.113883.2.1.3.2.4.18.48 University of Leeds

Woodhouse Lane

Leeds England LS2 9JT University Hospital Southampton NHS Foundation Trust

Southampton General Hospital Tremona Road

Southampton England SO16 6YD RHM@2.16.840.1.113883.2.1.3.2.4.18.48 Somerset NHS Foundation Trust

Trust Management Lydeard House Musgrove Park Hospital

Taunton England TA1 5DA RH5@2.16.840.1.113883.2.1.3.2.4.18.48 University Hospitals Plymouth NHS Trust

Derriford Hospital Derriford Road Derriford

Plymouth England PL6 8DH RK9@2.16.840.1.113883.2.1.3.2.4.18.48 Hampshire Hospitals NHS Foundation Trust

Basingstoke and North Hampshire Hos Aldermaston Road

Basingstoke England RG24 9NA RN5@2.16.840.1.113883.2.1.3.2.4.18.48 University Hospitals of Derby and Burton NHS Foundation Trust

Royal Derby Hospital Uttoxeter Road

Derby England DE22 3NE RTG@2.16.840.1.113883.2.1.3.2.4.18.48 The Newcastle upon Tyne Hospitals NHS Foundation Trust

Freeman Hospital Freeman Road High Heaton

Newcastle upon Tyne England NE7 7DN RTD@2.16.840.1.113883.2.1.3.2.4.18.48 Hull University Teaching Hospitals NHS Trust

Hull Royal Infirmary Anlaby Road

Hull England HU3 2JZ RWA@2.16.840.1.113883.2.1.3.2.4.18.48 Bradford Teaching Hospitals NHS Foundation Trust

Bradford Royal Infirmary Duckworth Lane

Bradford England BD9 6RJ RAE@2.16.840.1.113883.2.1.3.2.4.18.48 East Suffolk and North Essex NHS Foundation Trust

Colchester Dist General Hospital Turner Road

Colchester England CO4 5JL RDE@2.16.840.1.113883.2.1.3.2.4.18.48 North Bristol NHS Trust

Southmead Hospital Southmead Road Westbury-on-trym

Bristol England BS10 5NB RVJ@2.16.840.1.113883.2.1.3.2.4.18.48 Nottingham University Hospitals NHS Trust

Trust Headquarters Queens Medical Centre Derby Road

Nottingham England NG7 2UH RX1@2.16.840.1.113883.2.1.3.2.4.18.48 Royal Devon University Healthcare NHS Foundation Trust

Royal Devon University NHS Ft Barrack Road

Exeter England EX2 5DW RH8@2.16.840.1.113883.2.1.3.2.4.18.48 Liverpool University Hospitals NHS Foundation Trust

Royal Liverpool University Hospital Prescot Street

Liverpool England L7 8XP REM@2.16.840.1.113883.2.1.3.2.4.18.48 North Tees and Hartlepool NHS Foundation Trust

University Hospital of Hartlepool Holdforth Road

Hartlepool England TS24 9AH RVW@2.16.840.1.113883.2.1.3.2.4.18.48 York and Scarborough Teaching Hospitals NHS Foundation Trust

York Hospital Wigginton Road

York England YO31 8HE RCB@2.16.840.1.113883.2.1.3.2.4.18.48 Patient Current inclusion criteria as of 22/07/2026: 1. Aged ≥18 years 2. Undergone ERCP, sphincterotomy and duct clearance for common bile duct stones 3. Fit for and willing to undergo laparoscopic or robotic cholecystectomy 4. Able and willing to provide written informed consent 5. Able & willing to comply with the terms of the protocol, including completion of QoL questionnaires 6. Suitable for expectant management (in the opinion of the local investigator) Previous inclusion criteria: 1. Aged >=18 years 2. Undergone ERCP, sphincterotomy and duct clearance for common bile duct stones 3. Fit for and willing to undergo laparoscopic or robotic cholecystectomy 4. Able and willing to provide written informed consent 5. Able and willing to comply with the terms of the protocol, including completion of QoL questionnaires Mixed 18 Years 100 Years All 1318 0 Current exclusion criteria as of 22/07/2026: 1. Pregnancy or planned pregnancy 2. Gallbladder complications requiring urgent intervention, e.g., cholecystostomy insertion or endoscopic gallbladder drainage 3. Undergone previous cholecystectomy 4. Common bile duct stent in situ (unless biodegradable) 5. Pancreatic duct stent in situ (unless biodegradable) Previous exclusion criteria: 1. Pregnancy or planned pregnancy 2. Evidence of empyema or perforated gallbladder requiring urgent intervention 3. Cholecystostomy insertion 4. Undergone previous cholecystectomy 2025-06-27T00:00:00.000Z 2027-08-31T00:00:00.000Z Common bile duct stones Digestive System Current interventions as of 23/07/2026: ROSIER is an IDEAL stage 3, multicentre, pragmatic, unblinded, two-arm individually randomised controlled non-inferiority trial with an embedded group-sequential interim analysis to evaluate the effectiveness and cost-effectiveness of expectant management (EM) compared with laparoscopic cholecystectomy after endoscopic retrograde cholangiopancreatography (ERCP) for clearance of gallstones from the common bile duct. Expectant management means monitoring patients with the intention of not having surgery. Laparoscopic cholecystectomy is a keyhole operation to remove the gallbladder. Both treatment options are available to patients in routine NHS care. A 12-month internal pilot phase will assess recruitment feasibility and an integrated qualitative sub-study will assess: a) factors influencing trial participation, including willingness to randomise and be randomised b) experiences of the study interventions and process, c) factors likely to influence wider implementation of study findings. Trial population: The main trial will recruit 1318 adult participants, aged ≥ 18 years who have undergone ERCP, sphincterotomy and duct clearance for common bile duct stones who are fit to undergo surgery. Participants must be able and willing to give written informed consent and be able and willing to comply with the terms of the protocol, including completion of quality of life questionnaires. Site eligibility: The trial will open in approximately 33 NHS research sites across the UK. To be eligible to participate in the trial, research sites must meet the following criteria: 1. Be a secondary or tertiary care centre offering laparoscopic cholecystectomy 2. Offer ERCP 3. Have the anticipated capacity to recruit approximately 1-2 participants per month Participant identification and consent (main trial): Patients who have undergone ERCP, sphincterotomy and duct clearance for common bile duct stones will be screened for eligibility at participating research sites. Patients will be approached for possible recruitment into the trial following completion of ERCP for duct clearance and once they are considered fit for surgery. Suitability for inclusion in the trial will be assessed according to the trial eligibility criteria and patients will be provided with verbal and written details. A verbal explanation of the trial along with the approved Participant Information Sheet (PIS), will be provided by a suitably qualified member of the healthcare team for the patient to consider. The PIS will provide detailed information about the rationale, design and personal implications of the study. A PIS Supplementary Information Document, containing additional information about the trial, will also be provided to the participant. Reading the Supplementary Information Sheet is optional for patients and they do not need to read this document in order to consent to the ROSIER trial, if they do not wish to do so. Following information provision, patients will be given the opportunity to discuss the trial with their family and medically qualified members of the healthcare team before they are asked whether they would be willing to take part in the trial. Patients will be given as long as they need to consider participation in the trial, ideally this will be at least 24 hours. The right of the patient to refuse consent without giving reasons will be respected. Patients who wish to participate will be invited to provide written informed consent including explicit consent for the transfer of a copy of their signed consent form to the CTRU. Following consent patients will be formally assessed for eligibility. Informed consent may only be obtained by the Principal Investigator (PI) or an appropriate, delegated, healthcare professional or Clinical Research Practitioner. The healthcare professional/Clinical Research Practitioner must have knowledge of the trial interventions and have received training in the principles of GCP and the Declaration of Helsinki 1996. The healthcare professional/Clinical Research Practitioner must be fully trained in the trial according to the ethically approved protocol and be authorised and approved by the PI to take informed consent as documented in the trial Authorised Personnel Log. Randomisation: Participants will be randomised on an equal basis, using a computer-generated minimisation algorithm incorporating a random element, to undergo either expectant management or laparoscopic cholecystectomy. Randomisation will be based on a minimisation algorithm with random component, ensuring that treatment groups will be balanced for the following minimisation factors: • Cholangitis prior to ERCP (yes, no) • Obstructive jaundice without sepsis prior to ERCP (yes, no) • Pancreatitis prior to ERCP (yes, no) • Biliary pain or colic prior to ERCP (yes, no) • Cholecystitis prior to ERCP (yes, no) • Randomising Trust (derived from randomising site) Pre-operative investigations (only applicable to patients who undergo laparoscopic cholecystectomy): For participants who have laparoscopic cholecystectomy (LC), pre-operative investigations and preparation will be as per institutional protocol. This applies to all participants who undergo LC during their participation in the trial, whether they were randomised to the LC arm and have surgery, or they were randomised to expectant management but undergo LC. Interventions: Laparascopic cholecystectomy: For participants undergoing laparoscopic cholecystectomy, the operation should be performed as per institutional protocol, and by whichever surgeon would ordinarily carry out the procedure according to the local standard of care. LC may be performed using a laparoscopic or robotic approach. This applies to all participants who undergo LC during their participation in the trial, whether they were randomised to the LC arm and have surgery, or they were randomised to expectant management but undergo LC. Expectant management: EM participants will be managed with the intention of not undergoing cholecystectomy. EM will be at the discretion of the surgical team and according to local practice. During follow-up, if there is a clinical change, and it is clinically appropriate, surgery may occur as part of this treatment. If an EM patient requires LC for a clinically valid reason, for example, severe biliary pain, this will be compliant with the randomised treatment allocation. The participant will continue to be followed up until 24 months post-randomisation. Post-operative care (only applicable to participants who undergo laparoscopic cholecystectomy): For participants undergoing LC, post-operative care will be as per institutional protocol. This applies to all participants who undergo LC during their participation in the trial, whether they were randomised to the LC arm and have surgery, or they were randomised to expectant management but undergo LC. All participants (regardless of trial arm) will be followed up for trial purposes for 24 months post-randomisation. Trial follow-up: Clinical assessments: All participants will undergo a clinical review for trial purposes at 3, 6, 12 and 24 months post-randomisation. The trial follow-up assessments can be done via telephone if the participant is not due to be seen in clinic as part of local standard care at these timepoints, and will likely take around 15 minutes. Data collected at the clinical follow-ups will include (but will not be limited to): • Assessment details • Adverse events and severity • Need for further biliary intervention Any further clinical assessments/visits will be according to local standard clinical practice. Participant-completed questionnaires (3-monthly): Participants will complete a number of questionnaires designed to capture health-related quality of life and the costs involved with each treatment. All participants will complete the health-related quality of life questionnaire packs at baseline and then 3-monthly up to and including 24 months post-randomisation. Each questionnaire pack will consist of three validated questionnaires and a Health and Social Care Resource Use questionnaire, and will take approximately 30 minutes to complete. The baseline questionnaires will be administered to the participants by the local site research team and completed on paper. The baseline questionnaires should be completed after informed consent but prior to randomisation, or at least before the participant is informed of their randomisation result. The follow-up questionnaires will be administered directly to participants by the ROSIER CTRU trial team by SMS, email or post (depending on the participant's QoL completion preferences). If participants choose to complete their follow-up questionnaires in paper format via post, a freepost envelope will be provided so that they can return their completed questionnaire pack to the CTRU. Should a completed questionnaire not be received at the CTRU by the required time-point, the CTRU will send one reminder to the participant either by post, SMS or email (depending on the participant’s questionnaire-completion preferences). Monthly pain questionnaire: Participants will be asked to complete a short pain questionnaire, consisting of the two bodily pain domain questions of the SF36 survey, on a monthly basis in between the 3-monthly questionnaire packs throughout the 24-month follow-up period. The monthly pain questionnaire will ideally be completed by participants via SMS to minimise research burden, but participants will also have the option of completing this via email or on paper (via diary card), if they'd prefer. For paper completers, the diary card on which they can record their monthly pain responses for the next two months will be sent out alongside the 3-monthly questionnaire packs. Participants will then be able to return their completed diary card for the previous two months with their next 3-monthly pack. Pre-paid addressed envelopes will be provided for the return of the paper QoL questionnaires to CTRU. ERCP Central Review: As part of the trial eligibility criteria, all participants must have undergone ERCP (as per local standard practice) prior to being recruited to the ROSIER trial. ERCP details will be collected for all participants on the trial electronic case report forms. To validate the ERCP dataset, 10% of randomly selected occlusion cholangiogram images (taken during ERCP) and reports will be collected by the CTRU for central review. Hospital Episode Statistics (HES) Data Collection: Hospital admission data: Details of hospital admissions for biliary events, complications or treatment within 24 months of randomisation will be obtained from HES data. The CTRU trial team will submit a data access request to HES to obtain this data so there is no input required from sites. Readmissions (longer-term follow-up data): It is planned that late readmissions for biliary events, complications and treatment within 10 years post-randomisation will be derived from HES data. A separate ethics application and protocol will be submitted for this planned element of the research at an appropriate timepoint in the future. However, consent to collect the longer-term follow-up HES data will be obtained from trial participants from the outset as part of the main trial consent process - this is covered in the ROSIER Participant Information Sheet and Informed Consent Form. Qualitative sub-study: The qualitative sub-study incorporates mixed qualitative methods including interviews with patients and health professionals and audio-recording of recruitment conversations. Data collection and analysis will commence during study set-up and will focus on the internal pilot. The approach will be flexible and respond to project needs at the different stages of the trial. A summary of the activities in the sub-study is given below: Site survey: All participating sites will be asked to describe their current organisation of care for patients with bile duct stones (e.g. number of surgeons involved; number of procedures annually), including expectant management and perioperative LC management, and including any written information for patients. This will inform the purposive sample. Interviews with patients declining trial participation (during internal pilot only): During the internal pilot phase, patients (n = 10-12) who are approached for the ROSIER trial but decline to participate will be invited to take part in a single qualitative interview, which is anticipated to take around 45 minutes. Interviews with trial consenters (throughout the trial): Throughout the trial, a subset of participants who consent to take part in the ROSIER trial will be invited to take part in a qualitative interview (n = 24-28). Research site staff will invite all participants to consent to contact as part of the informed consent process for the main trial. Some patients may be asked to do a second interview to follow their experience over time. No patient will be asked to do more than two interviews. Each interview is anticipated to take approximately 45 minutes. To better understand patients' experience over time we will invite patients to contribute photos that communicate their experience of treatment or symptoms of bile duct stones (photo-elicitation). This will be optional. An amendment will be submitted for the materials relating to this element of the research prior to photos being requested from participants. Interviews with patients (both main trial consenters and decliners) will take place via telephone or video chat (e.g., via Microsoft Teams or Zoom). With permission from participants, the interviews will be audio-recorded, using digital encrypted recorders, or via the secure digital platform for interviews conducted virtually. Interviews with healthcare professionals (throughout the trial): Interviews with healthcare professionals involved in recruitment to ROSIER or in delivering the trial interventions(n = 24-30) will take place throughout the trial and are anticipated to take around 45 minutes each time. Most of the healthcare professional interviews will be done via telephone/virtual video conferencing platform (Microsoft Teams or Zoom), although some may be done face to face (for example, to coincide with a site observation). With permission from participants, the interviews will be audio-recorded, using digital encrypted recorders, or via the secure digital platform for interviews conducted virtually. GP focus groups: Two focus groups with GPs will be undertaken to understand primary care perspectives of the trial arms. Topic guides will be developed based on the initial findings from the ROSIER hospital health professional/patient interviews and will be submitted, with the relevant recruitment and consent materials, as an amendment. Audio recording of recruitment conversations: Sites taking part in the internal pilot will be asked to record their recruitment conversations with potential participants. A purposive sample of sites during the main trial (e.g. those struggling to recruit) will also be recruited (n= approximately 150 recordings in total across all sites - approximately 10 per site). Observation of ROSIER meetings (e.g. Site Initiation Visits and investigator meetings): It is planned that qualitative researchers will attend ROSIER meetings such as Site Initiation Visits and investigator meetings and make notes of points raised. During the internal pilot, site set-up meetings will be conducted to map trial and clinical pathways. Analysis will incorporate rapid qualitative analysis (during internal pilot); pen portrait and thematic analysis approaches and will be informed by Normalisation Process Theory. Timetable for research: There will be a 30-month recruitment period and all participants will be followed up until 24 months post-randomisation. The qualitative sub-study will run throughout the trial. One-sided superiority testing will be performed at two stages: in an interim analysis and at the full sample size of 1318 participants, prior to the non-inferiority analysis. The interim superiority analysis is estimated to require 530 participants with complete data – i.e., 664 (332 per arm) participants, assuming 20% attrition. Should superiority be demonstrated at either of these two stages the trial will close. The end of the trial is defined as the last participant's last data item within the 24-month follow-up period. _____ Previous interventions: ROSIER is an IDEAL stage 3, multicentre, pragmatic, unblinded, two-arm individually randomised controlled non-inferiority trial with an embedded group-sequential interim analysis to evaluate the effectiveness and cost-effectiveness of expectant management (EM) compared with laparoscopic cholecystectomy after endoscopic retrograde cholangiopancreatography (ERCP) for clearance of gallstones from the common bile duct. Expectant management means monitoring patients with the intention of not having surgery. Laparoscopic cholecystectomy is a keyhole operation to remove the gallbladder. Both treatment options are available to patients in routine NHS care. A 12-month internal pilot phase will assess recruitment feasibility and an integrated qualitative sub-study will assess: a) factors influencing trial participation, including willingness to randomise and be randomised b) experiences of the study interventions and process, c) factors likely to influence wider implementation of study findings. Trial population: The main trial will recruit 1318 adult participants, aged ≥ 18 years who have undergone ERCP, sphincterotomy and duct clearance for common bile duct stones who are fit to undergo surgery. Participants must be able and willing to give written informed consent and be able and willing to comply with the terms of the protocol, including completion of quality of life questionnaires. Site eligibility: The trial will open in approximately 33 NHS research sites across the UK. To be eligible to participate in the trial, research sites must meet the following criteria: 1. Be a secondary or tertiary care centre offering laparoscopic cholecystectomy 2. Offer ERCP 3. Have the anticipated capacity to recruit approximately 1-2 participants per month Participant identification and consent (main trial): Patients who have undergone ERCP, sphincterotomy and duct clearance for common bile duct stones will be screened for eligibility at participating research sites. Patients will be approached for possible recruitment into the trial following completion of ERCP for duct clearance and once they are considered fit for surgery. Suitability for inclusion in the trial will be assessed according to the trial eligibility criteria and patients will be provided with verbal and written details. A verbal explanation of the trial along with the approved Participant Information Sheet (PIS), will be provided by a suitably qualified member of the healthcare team for the patient to consider. The PIS will provide detailed information about the rationale, design and personal implications of the study. A PIS Supplementary Information Document, containing additional information about the trial, will also be provided to the participant. Reading the Supplementary Information Sheet is optional for patients and they do not need to read this document in order to consent to the ROSIER trial, if they do not wish to do so. Following information provision, patients will be given the opportunity to discuss the trial with their family and medically qualified members of the healthcare team before they are asked whether they would be willing to take part in the trial. Patients will be given as long as they need to consider participation in the trial, ideally this will be at least 24 hours. The right of the patient to refuse consent without giving reasons will be respected. Patients who wish to participate will be invited to provide written informed consent including explicit consent for the transfer of a copy of their signed consent form to the CTRU. Following consent patients will be formally assessed for eligibility. Informed consent may only be obtained by the Principal Investigator (PI) or an appropriate, delegated, healthcare professional or Clinical Research Practitioner. The healthcare professional/Clinical Research Practitioner must have knowledge of the trial interventions and have received training in the principles of GCP and the Declaration of Helsinki 1996. The healthcare professional/Clinical Research Practitioner must be fully trained in the trial according to the ethically approved protocol and be authorised and approved by the PI to take informed consent as documented in the trial Authorised Personnel Log. Randomisation: Participants will be randomised on an equal basis, using a computer-generated minimisation algorithm incorporating a random element, to undergo either expectant management or laparoscopic cholecystectomy. Randomisation will be based on a minimisation algorithm with random component, ensuring that treatment groups will be balanced for the following minimisation factors: • Cholangitis prior to ERCP (yes, no) • Obstructive jaundice without sepsis prior to ERCP (yes, no) • Pancreatitis prior to ERCP (yes, no) • Biliary pain or colic prior to ERCP (yes, no) • Cholecystitis prior to ERCP (yes, no) • Randomising site Pre-operative investigations (only applicable to patients who undergo laparoscopic cholecystectomy): For participants who have laparoscopic cholecystectomy (LC), pre-operative investigations and preparation will be as per institutional protocol. This applies to all participants who undergo LC during their participation in the trial, whether they were randomised to the LC arm and have surgery, or they were randomised to expectant management but undergo LC. Interventions: Laparascopic cholecystectomy: For participants undergoing laparoscopic cholecystectomy, the operation should be performed as per institutional protocol, and by whichever surgeon would ordinarily carry out the procedure according to the local standard of care. LC may be performed using a laparoscopic or robotic approach. This applies to all participants who undergo LC during their participation in the trial, whether they were randomised to the LC arm and have surgery, or they were randomised to expectant management but undergo LC. Expectant management: EM participants will be managed with the intention of not undergoing cholecystectomy. EM will be at the discretion of the surgical team and according to local practice. During follow-up, if there is a clinical change, and it is clinically appropriate, surgery may occur as part of this treatment. If an EM patient requires LC for a clinically valid reason, for example, severe biliary pain, this will be compliant with the randomised treatment allocation. The participant will continue to be followed up until 24 months post-randomisation. Post-operative care (only applicable to participants who undergo laparoscopic cholecystectomy): For participants undergoing LC, post-operative care will be as per institutional protocol. This applies to all participants who undergo LC during their participation in the trial, whether they were randomised to the LC arm and have surgery, or they were randomised to expectant management but undergo LC. All participants (regardless of trial arm) will be followed up for trial purposes for 24 months post-randomisation. Trial follow-up: Clinical assessments: All participants will undergo a clinical review for trial purposes at 3, 6, 12 and 24 months post-randomisation. The trial follow-up assessments can be done via telephone if the participant is not due to be seen in clinic as part of local standard care at these timepoints, and will likely take around 15 minutes. Data collected at the clinical follow-ups will include (but will not be limited to): • Assessment details • Adverse events and severity • Need for further biliary intervention Any further clinical assessments/visits will be according to local standard clinical practice. Participant-completed questionnaires (3-monthly): Participants will complete a number of questionnaires designed to capture health-related quality of life and the costs involved with each treatment. All participants will complete the health-related quality of life questionnaire packs at baseline and then 3-monthly up to and including 24 months post-randomisation. Each questionnaire pack will consist of three validated questionnaires and a Health and Social Care Resource Use questionnaire, and will take approximately 30 minutes to complete. The baseline questionnaires will be administered to the participants by the local site research team and completed on paper. The baseline questionnaires should be completed after informed consent but prior to randomisation, or at least before the participant is informed of their randomisation result. The follow-up questionnaires will be administered directly to participants by the ROSIER CTRU trial team by SMS, email or post (depending on the participant's QoL completion preferences). If participants choose to complete their follow-up questionnaires in paper format via post, a freepost envelope will be provided so that they can return their completed questionnaire pack to the CTRU. Should a completed questionnaire not be received at the CTRU by the required time-point, the CTRU will send one reminder to the participant either by post, SMS or email (depending on the participant’s questionnaire-completion preferences). Monthly pain questionnaire: Participants will be asked to complete a short pain questionnaire, consisting of the two bodily pain domain questions of the SF36 survey, on a monthly basis in between the 3-monthly questionnaire packs throughout the 24-month follow-up period. The monthly pain questionnaire will ideally be completed by participants via SMS to minimise research burden, but participants will also have the option of completing this via email or on paper (via diary card), if they'd prefer. For paper completers, the diary card on which they can record their monthly pain responses for the next two months will be sent out alongside the 3-monthly questionnaire packs. Participants will then be able to return their completed diary card for the previous two months with their next 3-monthly pack. Pre-paid addressed envelopes will be provided for the return of the paper QoL questionnaires to CTRU. ERCP Central Review: As part of the trial eligibility criteria, all participants must have undergone ERCP (as per local standard practice) prior to being recruited to the ROSIER trial. ERCP details will be collected for all participants on the trial electronic case report forms. To validate the ERCP dataset, 10% of randomly selected occlusion cholangiogram images (taken during ERCP) and reports will be collected by the CTRU for central review. Hospital Episode Statistics (HES) Data Collection: Hospital admission data: Details of hospital admissions for biliary events, complications or treatment within 24 months of randomisation will be obtained from HES data. The CTRU trial team will submit a data access request to HES to obtain this data so there is no input required from sites. Readmissions (longer-term follow-up data): It is planned that late readmissions for biliary events, complications and treatment within 10 years post-randomisation will be derived from HES data. A separate ethics application and protocol will be submitted for this planned element of the research at an appropriate timepoint in the future. However, consent to collect the longer-term follow-up HES data will be obtained from trial participants from the outset as part of the main trial consent process - this is covered in the ROSIER Participant Information Sheet and Informed Consent Form. Qualitative sub-study: The qualitative sub-study incorporates mixed qualitative methods including interviews with patients and health professionals and audio-recording of recruitment conversations. Data collection and analysis will commence during study set-up and will focus on the internal pilot. The approach will be flexible and respond to project needs at the different stages of the trial. A summary of the activities in the sub-study is given below: Site survey: All participating sites will be asked to describe their current organisation of care for patients with bile duct stones (e.g. number of surgeons involved; number of procedures annually), including expectant management and perioperative LC management, and including any written information for patients. This will inform the purposive sample. Interviews with patients declining trial participation (during internal pilot only): During the internal pilot phase, patients (n = 10-12) who are approached for the ROSIER trial but decline to participate will be invited to take part in a single qualitative interview, which is anticipated to take around 45 minutes. Interviews with trial consenters (throughout the trial): Throughout the trial, a subset of participants who consent to take part in the ROSIER trial will be invited to take part in a qualitative interview (n = 24-28). Research site staff will invite all participants to consent to contact as part of the informed consent process for the main trial. Some patients may be asked to do a second interview to follow their experience over time. No patient will be asked to do more than two interviews. Each interview is anticipated to take approximately 45 minutes. To better understand patients' experience over time we will invite patients to contribute photos that communicate their experience of treatment or symptoms of bile duct stones (photo-elicitation). This will be optional. An amendment will be submitted for the materials relating to this element of the research prior to photos being requested from participants. Interviews with patients (both main trial consenters and decliners) will take place via telephone or video chat (e.g., via Microsoft Teams or Zoom). With permission from participants, the interviews will be audio-recorded, using digital encrypted recorders, or via the secure digital platform for interviews conducted virtually. Interviews with healthcare professionals (throughout the trial): Interviews with healthcare professionals involved in recruitment to ROSIER or in delivering the trial interventions(n = 24-30) will take place throughout the trial and are anticipated to take around 45 minutes each time. Most of the healthcare professional interviews will be done via telephone/virtual video conferencing platform (Microsoft Teams or Zoom), although some may be done face to face (for example, to coincide with a site observation). With permission from participants, the interviews will be audio-recorded, using digital encrypted recorders, or via the secure digital platform for interviews conducted virtually. GP focus groups: Two focus groups with GPs will be undertaken to understand primary care perspectives of the trial arms. Topic guides will be developed based on the initial findings from the ROSIER hospital health professional/patient interviews and will be submitted, with the relevant recruitment and consent materials, as an amendment. Audio recording of recruitment conversations: Sites taking part in the internal pilot will be asked to record their recruitment conversations with potential participants. A purposive sample of sites during the main trial (e.g. those struggling to recruit) will also be recruited (n= approximately 150 recordings in total across all sites - approximately 10 per site). Observation of ROSIER meetings (e.g. Site Initiation Visits and investigator meetings): It is planned that qualitative researchers will attend ROSIER meetings such as Site Initiation Visits and investigator meetings and make notes of points raised. During the internal pilot, site set-up meetings will be conducted to map trial and clinical pathways. Analysis will incorporate rapid qualitative analysis (during internal pilot); pen portrait and thematic analysis approaches and will be informed by Normalisation Process Theory. Timetable for research: There will be a 30-month recruitment period and all participants will be followed up until 24 months post-randomisation. The qualitative sub-study will run throughout the trial. One-sided superiority testing will be performed at two stages: in an interim analysis and at the full sample size of 1318 participants, prior to the non-inferiority analysis. The interim superiority analysis is estimated to require 530 participants with complete data – i.e., 664 (332 per arm) participants, assuming 20% attrition. Should superiority be demonstrated at either of these two stages the trial will close. The end of the trial is defined as the last participant's last data item within the 24-month follow-up period. Procedure/Surgery Data sharing statement to be made available at a later date 1837f769-79f1-4422-9875-3395be117186 49b85053-5644-4169-a1fc-736a7e6163e2 f5d9c2c5-2562-4960-92d3-bcda2cde1ed6 a7416ae4-c758-43bf-91c3-0d3083bdfac0 6846bf7a-1002-401c-bb6f-628c6167e093 No Rachel Kelly Public

Clinical Trials Research Unit University of Leeds

Leeds United Kingdom LS2 9JT +44 (0)113 3436912 ROSIER@leeds.ac.uk Public Andrew Smith Principal investigator

Leeds Teaching Hospitals NHS Trust

Leeds United Kingdom LS9 7TF - andrewmsmith@nhs.net Public Giles Toogood Scientific

Leeds Teaching Hospitals NHS Trust

Leeds United Kingdom LS9 7TF - giles.toogood@nhs.net Public University of Leeds University/education https://ror.org/024mrxd33 Non-commercial National Institute for Health and Care Research http://dx.doi.org/10.13039/501100000272 93955714 true A digital approach to grief support and the treatment of post-loss mental health problems iCT-PG The primary objective is to assess the feasibility and acceptability of an internet-based cognitive therapy programme for Prolonged Grief (iCT-PG) in bereaved adults in order to establish the key parameters for a definitive RCT. The secondary research objective is to gather data on clinical outcomes to provide a preliminary indication of the clinical efficacy of the intervention (iCT-PG) for adults with a diagnosis of Prolonged Grief Disorder (PGD). The hypotheses related to clinical outcomes are: 1. Compared to waitlist, iCT-PG will reduce symptoms of PGD (post-treatment). 2. Compared to waitlist, iCT-PG will reduce symptoms of comorbid mental health problems (PTSD, depression, anxiety) and improve symptoms of social and occupational functioning (post-treatment). 3. Treatment effects will be maintained at follow-up. Background and study aims Prolonged grief disorder (PGD) is a condition where intense and long-lasting grief disrupts everyday life. This study tests a new online treatment called Internet-based Cognitive Therapy for Prolonged Grief (iCT-PG). The aim is to find out if this digital therapy is practical to use (feasible), acceptable to patients, and has the potential to improve grief symptoms. The treatment is designed to help people manage distressing memories of loss, challenge negative thoughts, adopt healthier coping strategies, and reduce feelings of social isolation. Who can participate? The study is open to adults aged 18 years and over who at assessment meet criteria for PGD. Participants can be referred through NHS Adult Talking Therapies services, general practitioners, or may self-refer via the study's website (https://grief.web.ox.ac.uk/). All participants must have regular access to the internet and be comfortable using a digital device for therapy. What does the study involve? Participants will be randomly assigned to one of two groups. One group will begin the digital therapy immediately while the other group will join a waitlist and start the treatment after 14 weeks. The online therapy includes 12 sessions delivered over 14 weeks, with weekly support calls from a trained therapist. The therapy is tailored to each person’s needs through a series of interactive online modules and an integrated smartphone app that offers support in real-time. Participants will complete weekly questionnaires during treatment measuring grief, anxiety, depression, and daily functioning and at four times once weekly treatment has ended (monthly for 3 months), and at follow-up (around Week 39). An independent assessor, who does not know which group participants are in, will also conduct interviews to objectively evaluate their symptoms. What are the possible benefits and risks of participating? Participating in this study gives individuals the opportunity to try a new digital treatment that could help ease the pain of prolonged grief. The benefits include access to flexible, expert therapist-supported online therapy that can be used from home. Additionally, the study will closely monitor how well the treatment works and how participants feel about it. However, it is not yet known whether the online therapies are more or less effective and acceptable to patients than face-to-face therapy. You should also be aware that some people may experience a temporary increase in distress as a result of remembering traumatic aspects of their loss during treatment, but this is usually short-lived. Where is the study run from? The study is managed by the University of Oxford, Department of Experimental Psychology, and is conducted in collaboration with NHS Adult Talking Therapies services (UK). When is the study starting and how long is it expected to run? February 2023 to June 2028 Who is funding the study? The study is funded by the Medical Research Council, Oxford Health Biomedical Research Centre, and the Wellcome Trust. Their support ensures that the research is conducted to a high standard and that the findings can inform future, larger trials. Who is the main contact? Dr Kirsten Smith, kirsten.smith@psy.ox.ac.uk Prolonged grief disorder symptoms measured with the International Prolonged Grief Disorder Scale (IPGDS) at baseline, 7, 15 weeks after random allocation (with follow-ups at 27, and 39), and weekly during treatment Current key secondary outcome(s) as of 05/05/2026: 1. Assessor ratings of PGD symptoms, assessed with a structured clinical interview at 15 weeks after random allocation (with follow-up at 27 weeks). 2. Other symptom measures assessed at baseline, 7, 15 weeks after random allocation (with follow-ups at 27 and 39 weeks), and some weekly during treatment: 2.1. Depression, assessed with the Patient Health Questionnaire (PHQ-9) 2.2. Anxiety, assessed with the Generalized Anxiety Disorder Scale 7-items (GAD-7) 2.3 Posttraumatic stress disorder with the PTSD checklist for DSM 5 (PCL-5) 2.4. Disability, assessed with the Work and Social Adjustment Scale (WSAS) 2.5. Sleep problems, assessed with the Insomnia Sleep Index (ISI) 2.6 Well-being, assessed with the Warwick Edinburgh Mental Wellbeing Scale (WEMBWS) 2.7 Alcohol use and dependence assessed with the Alcohol Use Disorders Identification Test (AUDIT) 3. Health economics measures (Euroqol EQ-5D-5L12, iMTA Productivity Cost Questionnaire (PCQ), Recovering Quality of Life (ReQoL-10), Client Service Receipt Inventory (CSRI), employment status and state benefits), assessed at baseline, 15, 27 and 39 weeks 4. Process measures assessed at baseline, 7, 15, 27, and 39 weeks after random allocation (and some weekly during treatment): 4.1. Excessively negative appraisals, assessed with the Oxford Grief Appraisals Scale (OG-A) 4.2. Memory characteristics, assessed with the Oxford Grief Memory Scale (OG-M) 4.3. Unhelpful strategies to deal with grief, assessed with the Oxford Grief Coping Strategies scale (OG-CS) 4.4 Social disconnection, assessed with the Oxford Grief Social Disconnection Scale (OG-SD) 4.5. Safety behaviours, assessed with the short version Safety Behaviours Questionnaire (SBQ) 4.6. Dissociation, assessed with the short version State-Trait Dissociation Questionnaire (TSDQ) Other process measures: 1. Therapeutic alliance, assessed using the Working Alliance Inventory (WAI) at weeks 2 and 7 2. Patient satisfaction and comments on their experience with online therapy, assessed using Online Treatment Experience Interview and the Talking Therapies adult patient experience questionnaire at week 15 _____ Previous key secondary outcome(s): 1. Assessor ratings of PGD symptoms, assessed with a structured clinical interview at 15 weeks after random allocation (with follow-up at 27 weeks). 2. Other symptom measures assessed at baseline, 7, 15 weeks after random allocation (with follow-ups at 27 and 39 weeks), and weekly during treatment: 2.1. Depression, assessed with the Patient Health Questionnaire (PHQ-9) 2.2. Anxiety, assessed with the Generalized Anxiety Disorder Scale 7-items (GAD-7) 2.3 Posttraumatic stress disorder with the PTSD checklist for DSM 5 (PCL-5) 2.4. Disability, assessed with the Work and Social Adjustment Scale (WSAS) 2.5. Sleep problems, assessed with the Insomnia Sleep Index (ISI) 2.6 Well-being, assessed with the Warwick Edinburgh Mental Wellbeing Scale (WEMBWS) 2.7 Alcohol use and dependence assessed with the Alcohol Use Disorders Identification Test (AUDIT) 3. Health economics measures (Euroqol EQ-5D-5L12, iMTA Productivity Cost Questionnaire (PCQ), Recovering Quality of Life (ReQoL-10), Client Service Receipt Inventory (CSRI), employment status and state benefits), assessed at baseline, 15, 27 and 39 weeks 4. Process measures assessed at baseline, 7, 15, 27, and 39 weeks after random allocation (and some weekly during treatment): 4.1. Excessively negative appraisals, assessed with the Oxford Grief Appraisals Scale (OG-A) 4.2. Memory characteristics, assessed with the Oxford Grief Memory Scale (OG-M) 4.3. Unhelpful strategies to deal with grief, assessed with the Oxford Grief Coping Strategies scale (OG-CS) 4.4 Social disconnection, assessed with the Oxford Grief Social Disconnection Scale (OG-SD) 4.5. Safety behaviours, assessed with the short version Safety Behaviours Questionnaire (SBQ) 4.6. Dissociation, assessed with the short version State-Trait Dissociation Questionnaire (TSDQ) Other process measures: 1. Therapeutic alliance, assessed using the Working Alliance Inventory (WAI) at weeks 2 and 7 2. Patient satisfaction and comments on their experience with online therapy, assessed using Online Treatment Experience Interview and the Talking Therapies adult patient experience questionnaire at week 15 Ethics approval required Yorkshire & The Humber - Bradford Leeds Research Ethics Committee

NHSBT Newcastle Blood Donor Centre, Holland Drive

Newcastle upon Tyne United Kingdom NE2 4NQ 23/YH/0061 10.1186/ISRCTN93955714 311815 CPMS: 55621 311815 55621 Randomized controlled trial Interventional Randomised controlled trial Treatment 2028-06-30T00:00:00.000Z United Kingdom England University of Oxford

Centre for Anxiety Disorders and Trauma Paradise Square

Oxford England OX1 1TW Oxford Health NHS Foundation Trust

Littlemore Mental Health Centre Sandford Road Littlemore

Oxford England OX4 4XN Patient Current key inclusion criteria as of 05/05/2026: 1. Aged 18 years and above 2. Willing and able to provide informed consent 3. Meets diagnostic criteria for PGD using the ICD-11 criteria and grief is the primary clinical concern 4. Able to read and write in English 5. Regular, private access to internet-enabled device and reliable internet connection 6. Have enough time in their week to be able to log in and work on the programme regularly (i.e. at least 20 mins on 3-4 days each week) 7. Willing to be randomly allocated to psychological treatment or waitlist 8. If on medication for mood/anxiety, the participant agrees not to change medication during the study. This is routine practice within TTAD services. For those patients who are already taking medication at the start of the psychological therapy, participants are asked not to change their medication while they are learning psychological skills for overcoming PGD in order to avoid complicating the clinical picture. Participants are required to have been on a stable dose of medication for at least 1 month before beginning treatment. 9. If currently receiving psychological therapy, this treatment must have ended before randomisation _____ Previous key inclusion criteria: 1. Aged 18 years and above 2. Willing and able to provide informed consent 3. Meets diagnostic criteria for PGD using the ICD-11 criteria 4. Able to read and write in English 5. Regular, private access to internet-enabled device and reliable internet connection 6. Have enough time in their week to be able to log in and work on the programme regularly (i.e. at least 20 mins on 3-4 days each week) 7. Willing to be randomly allocated to psychological treatment or waitlist 8. If on medication for mood/anxiety, the participant agrees not to change medication during the study. This is routine practice within TTAD services. For those patients who are already taking medication at the start of the psychological therapy, participants are asked not to change their medication while they are learning psychological skills for overcoming PGD in order to avoid complicating the clinical picture. 9. If currently receiving psychological therapy, this treatment must have ended before randomisation Mixed 18 Years 110 Years All 46 0 Current key exclusion criteria as of 05/05/2026: 1. History of psychosis 2. Current dependence on alcohol or substances 3. Current psychosis/bipolar affective disorder/emotionally unstable personality disorder (NB. These conditions are not typically treated within TTAD services) 4. Marked clinical risk based on the service’s intake assessment or the eligibility assessment 5. Currently participating in another clinical research study 6. Experience of an additional significant bereavement in the last 6 months (NB. To avoid disruption of the natural recovery process) _____ Previous key exclusion criteria: 1. History of psychosis 2. Current dependence on alcohol or substances 3. Current psychosis/bipolar affective disorder/emotionally unstable personality disorder (NB. These conditions are not typically treated within TTAD services) 4. Marked clinical risk based on the service’s intake assessment or the eligibility assessment 5. Currently participating in another clinical research study 2025-03-01T00:00:00.000Z 2028-01-31T00:00:00.000Z Prolonged grief disorder Mental and Behavioural Disorders Internet cognitive therapy for Prolonged Grief (iCT-PG) Participants will be randomly assigned to one of two groups. The method of randomisation will be Sealed Envelopes. Stratification factors will be by severity of PGD symptoms (above and equal to or below the median score from the developmental case series) and type of loss (lost child versus other relationship) varying block sizes of 2 and 4 will be used to minimize imbalance of patients allocated to immediate start or delayed start (14 weeks) One group will begin iCT-PG immediately while the other group will join a waitlist and start the treatment after 14 weeks. The online therapy includes 12 sessions delivered over 14 weeks, with weekly support calls from a trained therapist. The therapy is tailored to each person’s needs through a series of interactive online modules and an integrated smartphone app that offers support in real time. Participants will complete weekly questionnaires during treatment measuring grief, anxiety, depression, and daily functioning and four times once weekly treatment has ended (monthly for 3 months), and at follow-up (around Week 39). An independent assessor, who does not know which group participants are in, will also conduct interviews to objectively evaluate their symptoms. Other The Medical Research Council has a policy of data sharing. Therefore, only data that can be reliably anonymised (e.g. demographics, loss characteristics, and symptom outcomes as well as the engagement data (e.g. of time spent online, mobile app use, audiovisual downloads, online contact with therapist) will be available to other researchers via ORA-Data. ORA-Data is a searchable repository in the Oxford catalogue of research data https://ora.ox.ac.uk/. A webpage will be created on the Oxford Centre for Anxiety Disorders and Trauma (OxCADAT) website which will describe the available data and metadata. Participants will be made aware of the categories of anonymised data that will be stored for sharing purposes in the information sheet. Researchers wishing to access the data can submit a proposal to the study team via the ORA-Data site. Requests will be approved assuming that release does not (i) risk disclosure of participant identity; (ii) violate any ethico-legal or other stipulations that apply to the data; or (iii) run the risk of harming the study as a whole or any participants in it. Stored in non-publicly available repository

Migrated from study website field

049e7932-cacb-4c7c-ac84-e0448acd8dbc 9856e092-76d7-4f91-9ed2-b9881e0ba61e 04aa1cda-99a1-4f6f-ad2f-3a9f124acd41 7d786ad9-af6c-49d3-9f58-ad82e23ad9a3 b6968ce1-b040-4e90-aab9-d736fb617c6f 9d9d3a69-ff43-486b-b6ca-7513a6739c17 Yes Kirsten Smith https://orcid.org/0000-0002-6973-2846 Scientific Principal investigator

Centre for Anxiety Disorders and Trauma The Old Rectory, Paradise Square

Oxford United Kingdom OX1 1TW +44 (0)7814457653 kirsten.smith@psy.ox.ac.uk Public Danai Athanasoula Public

Centre for Anxiety Disorders and Trauma The Old Rectory, Paradise Square

Oxford United Kingdom OX1 1TW - grief@psy.ox.ac.uk Public University of Oxford University/education https://ror.org/052gg0110 Non-commercial Medical Research Council http://dx.doi.org/10.13039/501100000265 Oxford Health Biomedical Research Centre Wellcome Trust