Abstract Background and aims Depression affects approximately one-third of stroke survivors and is associated with poorer recovery, increased morbidity and reduced quality of life. Evidence for early psychological interventions post-stroke remains limited. Motivational Interviewing-Based Intervention (MIBI) is a person-centred therapy with promising preliminary evidence. COMMITS evaluated the clinical, and cost-effectiveness of MIBI in reducing depressive symptoms compared with attention control (AC) or usual care (UC). Methods COMMITS was a multicentre, three-arm, parallel-group randomised controlled trial conducted across 16 UK stroke units. Adults within 12 weeks post-stroke, able to consent, with PHQ-9≤14 and not receiving psychological therapy were randomised 1:1:1 to MIBI+UC:AC+UC:UC alone. Randomisation used stochastic minimisation over site, age, baseline mood and preferred session format (phone/on-line). MIBI and AC comprised four 45-minute sessions delivered remotely by trained staff. The primary outcome was PHQ-9 score at 3 months post-randomisation. Resource use and EQ-5D-5L were collected for economic evaluation. Outcomes were analysed as intention-to-treat using mixed-effects models with site and therapist as random effects and minimisation factors and baseline value of the outcome measure as fixed effects. Results Of 14,047 patients screened, 1,246 were randomised (MIBI+UC n=415; AC+UC n=415; UC n=416). Completion of all 4 sessions was high (MIBI 66.5%; AC 58.1%). Data collection is complete, and primary outcome were available for 65% of participants. Conclusions Clinical effectiveness and cost-effectiveness outcomes will be presented. COMMITS will establish whether mood changes reflect natural recovery, non-specific attention effects, or a specific therapeutic benefit of MIBI. Conflict of interest

OBJECTIVE:People with inflammatory arthritis (InfA) frequently experience work instability, absenteeism, and reduced productivity, culminating in early job loss. This study evaluated the effectiveness and cost-effectiveness of WORKWELL job retention vocational rehabilitation (JRVR) delivered by occupational therapists, compared with a control group receiving written self-help advice. METHODS:A pragmatic, multicentre randomized controlled trial was conducted across 18 UK National Health Service (NHS) Trusts. Employed adults (n = 249) with InfA experiencing moderate to severe work instability were randomized (1:1) to intervention or control groups. WORKWELL included structured work assessment, individually tailored action plans, and interventions over 2-4 months. Follow-up was at 6, 12 and 36 months. The primary outcome was measured using the Work Limitations Questionnaire-25 (WLQ-25). Analyses used linear mixed-effects regression adjusted for baseline characteristics and occupational skill level. A NHS perspective was used for the within-trial cost-effectiveness analysis. Much of the trial was affected by the COVID-19 pandemic. RESULTS:At 12 months, there was no significant difference in WLQ-25 between groups (adjusted mean difference: -1.8; 95% CI -7.4-3.8; P = 0.53), or in most secondary outcomes at 12 or 36 months. However, absenteeism showed a relative reduction of 46% at 12 months (P = 0.08), and employment retention at 36 months was higher in the intervention (93%) than in the control group (85%). The intervention was not cost-effective from an NHS perspective. CONCLUSION:WORKWELL did not lead to improved work productivity compared with self-help advice. Future research should explore more flexible delivery methods, including digital tools, to support sustainable employment for people with InfA. A plain-language abstract is available in the supplementary material. TRIAL REGISTRATION:ClinicalTrials.gov, http://clinicaltrials.gov, NCT03942783. ISRCTN Registry, ISRCTN61762297, https://doi.org/10.1186/ISRCTN61762297.

Palliative radiotherapy is widely used in stage IV non-small cell lung cancer (NSCLC). Radiotherapy dose fractionation studies have shown its utility in symptom control with improved survival at higher doses. Recent advances in radiotherapy planning and delivery offer dose escalation while reducing toxicity. However, there are no studies testing palliative radiotherapy in combination with modern systemic therapies and trials are needed to test timing, dose and fractionation in that context.

Abstract Background The primary objective of this UK-based trial was to investigate the feasibility of conducting a multi-centre randomised controlled evaluation trial of Empowered Conversations (EC). EC is a 6-session group psychosocial intervention for informal (family) care partners of people living with dementia. The two key feasibility objectives were to establish whether recruitment levels and retention to follow-up were sufficient for a multi-centre evaluation trial to be feasible. Secondary objectives were as follows: to estimate potential effectiveness on a range of candidate primary outcome measures and their standard deviations; to identify the most appropriate primary outcome measure for a multi-centre evaluation trial; to obtain additional evidence regarding proof of concept; to establish the optimum way of evaluating cost-effectiveness in the evaluation trial. Methods The feasibility trial used a pragmatic data-collector blind parallel two-group RCT design with two arms (EC intervention plus treatment as usual, and treatment as usual waitlist control). There was a 2:1 allocation in favour of the EC arm. Participants completed baseline outcome measures including measures of their psychological health, quality of life and service use. These were repeated after 6 months. Results Seventy-five care partners were recruited. The average number of people randomised per month was 8.9, consistent with the pre-specified average recruitment rate of 6 to 10 carers per month sufficient for proceeding to a multi-centre trial. A total of 58 (77%) participants were retained at 6 months follow-up meeting the amber stop-go criterion (65%–<80%; green ≥ 80% retention). Conclusion The trial indicated the feasibility of progressing to an evaluation trial of EC. Recruitment was at a sufficient level for a multi-centre trial across three proposed sites. Retention to follow-up was close to the green criterion, and ways of increasing retention in the evaluation trial have been identified. Trial Registration ISRCTN15261686; Registered 02/03/2022 https://www.isrctn.com/ISRCTN15261686

Background:Stroke is increasing in low- and middle-income countries. Stroke unit care, including evidence-based practice such as swallowing and hydration protocols, is associated with reduced disability and mortality. Objectives:The aim of this study is to codesign a swallowing and hydration care bundle for nurses to use with acute stroke patients, and to implement and evaluate the bundle on three acute stroke units across India. Methods:A multicentre, preimplementation and postimplementation feasibility study was conducted. We codesigned a care bundle (with stakeholders) which included the Global Evaluation of Swallowing and hydration screening and related actions/management. Implementation used clinical champions, education and training, barrier and enabler identification and site support. Participants included consecutively admitted patients, aged ≥ 18 years, with a clinical diagnosis of acute stroke and a persistent neurological deficit on presentation, who were admitted to a study site within 2 weeks of stroke onset. Results:Fifty-three healthcare staff completed the care bundle training. We recruited 183 participants, preimplementation group (n = 92). Swallowing evaluations using different consistencies increased from 22 (23.9%) to 51 (56%). Calculated osmolarity (cOsm) increased from 0 to 66 (73%) participants. Median cOsm was 288 mmol/L (IQR: 280-295 mmol/L); 15 (23%) participants were dehydrated. Conclusion:Care bundle implementation was feasible and improved swallowing and hydration management in three sites in India.

Introduction The real-world treatment effect of a novel treatment can be estimated by analysing routinely collected patient data, in the form of Electronic Health Records (EHR). Any treatment allocation in EHR is not randomised and there may be systematic differences between the treatment groups. Propensity Score (PS) methods are commonly used to correct for these differences and reduce the bias in the treatment effect estimate. The aims of the study were to compare the performance of the most popular PS methods in the estimation of the treatment effect in the presence of two common issues in EHRs: covariate measurement error and sparse data.Methods The motivational example for this study was the assessment of the treatment effect of the novel oral anti-coagulant Rivaroxaban compared with the previous standard treatment Warfarin for the prevention of future stroke in patients with atrial fibrillation. Using simulation experiments based on a dataset comparing Rivaroxaban with Warfarin, we evaluated the performance of four PS methods.Results In the simulations with characteristics of the original dataset, using 3:1 PS matching generated a largest bias of +0.0428 (corresponding ratio of HRs (rHR) 1.0437), whereas for the other PS methods it was smaller and in negative direction: IPTW for ATE -0.0181 (rHR = 0.9821); IPTW for ATT -0.0110 (rHR = 0.9891); PS stratification -0.0099 (rHR = 0.9901), with relative differences between rHRs being small to negligible. Fifty percent under-recording of a covariate (stroke) in the PS model, increased the MSE between 6% and 11% compared to the MSE with no introduced measurement error. While 50% over-recording reduced the MSE by around 35%. The difference in the bias of the low prevalence outcome (0.5%) and the high prevalence outcome (10%) was: IPTW for ATE 0.1514 (rHRs = 1.1635); IPTW for ATT 0.0160 (rHRs = 1.0161); 3:1 PS matching 0.0758 (rHRs = 1.0787); PS Stratification 0.0177 (rHRs = 1.0179). A similar pattern for outcome prevalence was seen for all the simulation scenarios.Conclusion This study showed that PS methods proposed in the literature may not all perform well for individual datasets. The findings produced recommendations for using PS methods in the estimation of real-world treatment effect when the covariate measurement error and sparse outcome data are present.

The Broad-Minded Affective Coping (BMAC) intervention is a theory-driven cognitive therapy aiming to reduce suicidal ideation through guided positive mental imagery. We explored the feasibility and acceptability of a randomised controlled trial to evaluate the BMAC intervention in university students. The trial was a two-arm, randomised (ratio 1:1) controlled feasibility trial comparing risk assessment and signposting with or without the BMAC intervention (ISRCTN 13621293; ClinicalTrials.gov NCT05296538). Participants had recent suicidal ideation or behaviour. Feasibility outcomes concerned recruitment, retention, intervention adherence, completion of a suicidal ideation assessment, and the safety of the procedures. Clinical outcomes and putative mechanisms were recorded at baseline and after eight, 16, and 24-weeks. All feasibility criteria were met. Sixty-five participants were randomized (99 % of target sample). Retention to follow-up was high at all timepoints (89-91 %). In the treatment arm, 30 out of 33 participants (91 %) attended ≥2 sessions of the BMAC. Retained participants completed a suicidal ideation assessment with no missing data. There were 19 serious adverse events, but none were related to the trial procedures or intervention. Effect estimates for suicidal ideation favoured the intervention. The trial and intervention were acceptable, feasible, and safe. The efficacy of the intervention requires evaluation in a definitive trial.

Objective: We previously showed that intermittently scanned continuous glucose monitoring (isCGM) reduces HbA1c at 24 weeks compared with self-monitoring of blood glucose with finger pricking (SMBG) in adults with type 1 diabetes and high HbA1c levels (58-97 mmol/mol [7.5%-11%]). We aim to assess the economic impact of isCGM compared with SMBG.Methods: Participant-level baseline and follow-up health status (EQ-5D-5L) and within-trial healthcare resource-use data were collected. Quality-adjusted life-years (QALYs) were derived at 24 weeks, adjusting for baseline EQ-5D-5L. Participant-level costs were generated. Using the IQVIA CORE Diabetes Model, economic analysis was performed from the National Health Service perspective over a lifetime horizon, discounted at 3.5%.Results: Within-trial EQ-5D-5L showed non-significant adjusted incremental QALY gain of 0.006 (95% CI: -0.007 to 0.019) for isCGM compared with SMBG and an adjusted cost increase of 548 pound (95% CI: 381-714) per participant. The lifetime projected incremental cost (95% CI) of isCGM was 1954 pound (-5108 to 8904) with an incremental QALY (95% CI) gain of 0.436 (0.195-0.652) resulting in an incremental cost-per-QALY of 4477 pound. In all subgroups, isCGM had an incremental cost-per-QALY better than 20,000 pound compared with SMBG; for people with baseline HbA1c >75 mmol/mol (9.0%), it was cost-saving. Sensitivity analysis suggested that isCGM remains cost-effective if its effectiveness lasts for at least 7 years.Conclusion: While isCGM is associated with increased short-term costs, compared with SMBG, its benefits in lowering HbA1c will lead to sufficient long-term health-gains and cost-savings to justify costs, so long as the effect lasts into the medium term.

BackgroundApproximately every 16 seconds a baby dies, before, during or shortly after birth globally. Over 98% of stillbirths and neonatal deaths occur in low- and middle-income countries, with over 75% in sub-Saharan Africa and South Asia. Alongside prevention, providing respectful and appropriate bereavement support to parents is a key global priority for equitable care and outcomes. Previous studies in sub-Saharan Africa, including Kenya and Uganda, demonstrate limited bereavement support in facilities and stigma surrounding perinatal death in communities. There is an urgent need for context-appropriate interventions to improve emotional and psychological support for bereaved parents in these settings.ObjectivesTo assess the feasibility of implementation, and a full-scale effectiveness evaluation of a co-produced multicomponent intervention to improve perinatal bereavement support in Kenya and Uganda.DesignA prospective, observational, mixed-methods feasibility study, using a pre- and post-cohort design. Community engagement and involvement was embedded throughout the research process.SettingTwo tertiary urban maternity facilities and surrounding communities in Kenya and Uganda.ParticipantsPostnatal women experiencing stillbirth or early neonatal death in the included facilities.InterventionTwo components including (1) introduction of trained health worker ‘bereavement champions’ in facilities, focused on developing care for bereaved women and families through individual and collective action and (2) access to telephone peer support for women, post discharge, from trained peers in communities.Main outcome measuresThe primary feasibility outcome measures were recruitment and retention of women. Secondary outcomes included acceptability of the intervention and research processes, feasibility of data collection, characteristics of the proposed evaluation trial primary outcome measure and quality of implementation.ResultsOver the study period, November 2019 to December 2020, a total of 501 women experienced stillbirth or early neonatal death in the included facilities, 208 women consented to be contacted for participation in the study and 107 were recruited; 56 women experiencing usual postnatal care and 51 offered the study intervention. Despite the COVID-19 pandemic, recruitment was 89% of the target and 85% of participants completed the study. The intervention was implemented largely as planned and was generally acceptable to women, families, health workers and others involved. Key learning points included the need for education for a wider group of health workers to increase understanding of principles of effective bereavement support and involving more clinical leaders as bereavement champions, to add leverage for change in practice. Research processes and data collection tools, including the selected psychological measures, were also acceptable. Women and families welcomed the opportunity to participate in research to improve care.LimitationsThis study was impacted by COVID-19, which disrupted aspects of recruitment, intervention implementation and data collection. The focus on urban settings in both countries is a potential limitation to transferability of findings.ConclusionsThis study demonstrated the feasibility of implementation and of a larger-scale effectiveness evaluation of the co-produced multicomponent intervention. Learning from this feasibility study will be used to refine the intervention to improve context-appropriateness.Future workA pragmatic stepped-wedge cluster-randomised controlled trial, with parallel economic and process evaluations is proposed to assess the clinical and cost effectiveness of the intervention and explore future scale-up and sustainability.FundingThis article presents independent research funded by the National Institute for Health and Care Research (NIHR)Global Health Researchprogramme as award number GHR 16/137/53.

The Method of Levels (MOL) is a theoretically-informed, transdiagnostic cognitive therapy that could improve service user engagement and recovery for individuals with early psychosis. We aimed to assess the feasibility and acceptability of training care coordinators in early intervention in psychosis teams to deliver MOL, and to assess the feasibility of conducting a two-arm parallel-group cluster-randomised controlled trial (C-RCT) with randomisation at the level of teams. Randomisation was in a ratio of 1:2 to either (1: control) treatment as usual (TAU); or (2: intervention) TAU plus support from a care coordinator who has received training in MOL. Clinical and health economic outcomes were collected at baseline, three, and six months. Fourteen early intervention in psychosis teams (117% of target), 31 care coordinators (129% of target), and 49 service users (51% of target) were recruited. Results suggest that some aspects of this study are feasible in their current form (e.g., care coordinator recruitment), other aspects are likely to be feasible with relatively minor adjustments (e.g., service user retention), and some aspects would need substantial changes to make the delivery of an evaluation C-RCT feasible (e.g., service user recruitment; MOL supervision for care coordinators). Progression to an evaluation trial would be justified if plausible solutions can be found to address the feasibility issues identified in this study.

Background Randomised controlled trials (‘trials’) are susceptible to poor participant recruitment and retention. Studies Within A Trial are the strongest methods for testing the effectiveness of strategies to improve recruitment and retention. However, relatively few of these have been conducted. Objectives PROMoting THE Use of Studies Within A Trial aimed to facilitate at least 25 Studies Within A Trial evaluating recruitment or retention strategies. We share our experience of delivering the PROMoting THE Use of Studies Within A Trial programme, and the lessons learnt for undertaking randomised Studies Within A Trial. Design A network of 10 Clinical Trials Units and 1 primary care research centre committed to conducting randomised controlled Studies Within A Trial of recruitment and/or retention strategies was established. Promising recruitment and retention strategies were identified from various sources including Cochrane systematic reviews, the Study Within A Trial Repository, and existing prioritisation exercises, which were reviewed by patient and public members to create an initial priority list of seven recruitment and eight retention interventions. Host trial teams could apply for funding and receive support from the PROMoting THE Use of Studies Within A Trial team to undertake Studies Within A Trial. We also tested the feasibility of undertaking co-ordinated Studies Within A Trial, across multiple host trials simultaneously. Setting Clinical trials unit-based trials recruiting or following up participants in any setting in the United Kingdom were eligible. Participants Clinical trials unit-based teams undertaking trials in any clinical context in the United Kingdom. Interventions Funding of up to £5000 and support from the PROMoting THE Use of Studies Within A Trial team to design, implement and report Studies Within A Trial. Main outcome measures Number of host trials funded. Results Forty-two Studies Within A Trial were funded (31 host trials), across 12 Clinical Trials Units. The mean cost of a Study Within A Trial was £3535. Twelve Studies Within A Trial tested the same strategy across multiple host trials using a co-ordinated Study Within A Trial design, and four used a factorial design. Two recruitment and five retention strategies were evaluated in more than one host trial. PROMoting THE Use of Studies Within A Trial will add 18% more Studies Within A Trial to the Cochrane systematic review of recruitment strategies, and 79% more Studies Within A Trial to the Cochrane review of retention strategies. For retention, we found that pre-notifying participants by card, letter or e-mail before sending questionnaires was effective, as was the use of pens, and sending personalised text messages to improve questionnaire response. We highlight key lessons learnt to guide others planning Studies Within A Trial, including involving patient and public involvement partners; prioritising and selecting strategies to evaluate and elements to consider when designing a Study Within A Trial; obtaining governance approvals; implementing Studies Within A Trial, including individual and co-ordinated Studies Within A Trials; and reporting Study Within A Trials. Limitations The COVID-19 pandemic negatively impacted five Studies Within A Trial, being either delayed ( n = 2) or prematurely terminated ( n = 3). Conclusions PROMoting THE Use of Studies Within A Trial significantly increased the evidence base for recruitment and retention strategies. When provided with both funding and practical support, host trial teams successfully implemented Studies Within A Trial. Future work Future research should identify and target gaps in the evidence base, including widening Study Within A Trial uptake, undertaking more complex Studies Within A Trial and translating Study Within A Trial evidence into practice. Study registration All Studies Within A Trial in the PROMoting THE Use of Studies Within A Trial programme had to be registered with the Northern Ireland Network for Trials Methodology Research Study Within A Trial Repository. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/55/80) and is published in full in Health Technology Assessment ; Vol. 28, No. 2. See the NIHR Funding and Awards website for further award information.

AIMS:The FLASH-UK trial showed lower HbA1c with intermittently scanned continuous glucose monitoring (isCGM), as compared with self monitoring of blood glucose (SMBG), in adults with type 1 diabetes and HbA1c ≥58 mmol/mol (≥7.5%). Here, we present results from the pre-specified subgroup analysis for the 24-week HbA1c (primary outcome) and selected sensor-based secondary outcomes. METHODS:This was a multi-centre, parallel-design, randomised controlled trial. The difference in treatment effect between subgroups (baseline HbA1c [≤75 vs. >75 mmol/mol] [≤9.0 vs >9.0%], treatment modality [pump vs injections], prior participation in structured education, age, educational level, impaired awareness of hypoglycaemia, deprivation index quintile sex, ethnic group and Patient Health Questionnaire-9 [PHQ-9] detected depression category) were evaluated. RESULTS:One hundred fifty-six participants (females 44%, mean [SD] baseline HbA1c 71 [9] mmol/mol 8.6 [0.8%], age 44 [15]) were randomly assigned, in a 1:1 ratio to isCGM (n = 78) or SMBG (n = 78). The mean (SD) baseline HbA1c (%) was 8.7 (0.9) in the isCGM group and 8.5 (0.8) in the SMBG group, lowering to 7.9 (0.8) versus 8.3 (0.9), respectively, at 24 weeks (adjusted mean difference -0.5, 95% confidence interval [CI] -0.7 to -0.3; p < 0.001]. For HbA1c, there was no impact of treatment modality, prior participation in structured education, deprivation index quintile, sex or baseline depression category. The between-group difference in HbA1c was larger for younger people (a reduction of 2.7 [95% CI 0.3-5.0; p = 0.028] mmol/mol for every additional 15 years of age). Those with HbA1c 76-97 mmol/mol (>9.0%-11.0%) had a marginally non-significant higher reduction in HbA1c of 8.4 mmol/mol (3.3-13.5) compared to 3.1 (0.3-6.0) in those with HbA1c 58-75 mmol/mol (p = 0.08). For 'Time in range' (% 3.9-10 mmol/L), the difference was larger for those with at least a bachelor's degree. For 'Time below range' (% <3.9 mmol/L), the difference was larger for those using injections, older people and those with less than bachelor's degree. CONCLUSIONS:Intermittently scanned continuous glucose monitoring is generally effective across a range of baseline characteristics.

Background: The intracluster correlation coefficient is a key input parameter for sample size determination in cluster-randomised trials. Sample size is very sensitive to small differences in the intracluster correlation coefficient, so it is vital to have a robust intracluster correlation coefficient estimate. This is often problematic because either a relevant intracluster correlation coefficient estimate is not available or the available estimate is imprecise due to being based on small-scale studies with low numbers of clusters. Misspecification may lead to an underpowered or inefficiently large and potentially unethical trial. Methods: We apply a Bayesian approach to produce an intracluster correlation coefficient estimate and hence propose sample size for a planned cluster-randomised trial of the effectiveness of a systematic voiding programme for post-stroke incontinence. A Bayesian hierarchical model is used to combine intracluster correlation coefficient estimates from other relevant trials making use of the wealth of intracluster correlation coefficient information available in published research. We employ knowledge elicitation process to assess the relevance of each intracluster correlation coefficient estimate to the planned trial setting. The team of expert reviewers assigned relevance weights to each study, and each outcome within the study, hence informing parameters of Bayesian modelling. To measure the performance of experts, agreement and reliability methods were applied. Results: The 34 intracluster correlation coefficient estimates extracted from 16 previously published trials were combined in the Bayesian hierarchical model using aggregated relevance weights elicited from the experts. The intracluster correlation coefficients available from external sources were used to construct a posterior distribution of the targeted intracluster correlation coefficient which was summarised as a posterior median with a 95% credible interval informing researchers about the range of plausible sample size values. The estimated intracluster correlation coefficient determined a sample size of between 450 (25 clusters) and 480 (20 clusters), compared to 500–600 from a classical approach. The use of quantiles, and other parameters, from the estimated posterior distribution is illustrated and the impact on sample size described. Conclusion: Accounting for uncertainty in an unknown intracluster correlation coefficient, trials can be designed with a more robust sample size. The approach presented provides the possibility of incorporating intracluster correlation coefficients from various cluster-randomised trial settings which can differ from the planned study, with the difference being accounted for in the modelling. By using expert knowledge to elicit relevance weights and synthesising the externally available intracluster correlation coefficient estimates, information is used more efficiently than in a classical approach, where the intracluster correlation coefficient estimates tend to be less robust and overly conservative. The intracluster correlation coefficient estimate constructed is likely to produce a smaller sample size on average than the conventional strategy of choosing a conservative intracluster correlation coefficient estimate. This may therefore result in substantial time and resources savings.