Biomarker Driven Antifungal Stewardship (BioDriveAFS) in acute leukaemia-a multi-centre randomised controlled trial to assess clinical and cost effectiveness: a study protocol for a randomised controlled trial.

BACKGROUND: Acute leukaemias (AL) are life-threatening blood cancers that can be potentially cured with treatment involving myelosuppressive, multiagent, intensive chemotherapy (IC). However, such treatment is associated with a risk of serious infection, in particular invasive fungal infection (IFI) associated with prolonged neutropenia. Current practice guidelines recommend primary antifungal (AF) prophylaxis to be administered to high-risk patients to reduce IFI incidence. AFs are also used empirically to manage prolonged neutropenic fever. Current strategies lead to substantial overuse of AFs. Galactomannan (GM) and ß-D-glucan (BG) biomarkers are also used to diagnose IFI. Combining both biomarkers may enhance the predictability of IFI compared to administering each test alone. Currently, no large-scale randomised controlled trial (RCT) has directly compared a biomarker-based diagnostic screening strategy without AF prophylaxis to AF prophylaxis (without systematic biomarker testing). METHODS: BioDriveAFS is a multicentre, parallel, two-arm RCT of 404 participants from UK NHS Haematology departments. Participants will be allocated on a 1:1 basis to receive either a biomarker-based antifungal stewardship (AFS) strategy, or a prophylactic AF strategy, which includes existing standard of care (SoC). The co-primary outcomes will be AF exposure in the 12-month post randomisation and the patient-reported EQ-5D-5L measured at 12-month post randomisation. Secondary outcomes will include total AF exposure, probable/proven IFI, survival (all-cause mortality and IFI mortality), IFI treatment outcome, AF-associated adverse effects/events/complications, resource use, episodes of neutropenic fever requiring hospital admission or outpatient management, AF resistance in fungi (non-invasive and invasive) and a Desirability of Outcome Ranking. The trial will have an internal pilot phase during the first 9 months. A mixed methods process evaluation will be integrated in parallel to the internal pilot phase and full trial, aiming to robustly assess how the intervention is delivered. Cost-effectiveness analysis will also be performed. DISCUSSION: The BioDriveAFS trial aims to further the knowledge of strategies that will safely optimise AF use through comparison of the clinical and cost-effectiveness of a biomarker-led diagnostic strategy versus prophylactic AF to prevent and manage IFI within acute leukaemia. The evidence generated from the study will help inform global clinical practice and approaches within antifungal stewardship. TRIAL REGISTRATION: ISRCTN11633399. Registered 24/06/2022.

Smoking, nicotine and pregnancy 2 (SNAP2) trial: protocol for a randomised controlled trial of an intervention to improve adherence to nicotine replacement therapy during pregnancy.

INTRODUCTION: Smoking during pregnancy is harmful to unborn babies, infants and women. Nicotine replacement therapy (NRT) is offered as the usual stop-smoking support in the UK. However, this is often used in insufficient doses, intermittently or for too short a time to be effective. This randomised controlled trial (RCT) explores whether a bespoke intervention, delivered in pregnancy, improves adherence to NRT and is effective and cost-effective for promoting smoking cessation. METHODS AND ANALYSIS: A two-arm parallel-group RCT was conducted for pregnant women aged ≥16 years and who smoke ≥1 daily cigarette (pre-pregnancy smoked ≥5) and who agree to use NRT in an attempt to quit. Recruitment is from antenatal care settings and via social media adverts. Participants are randomised using blocked randomisation with varying block sizes, stratified by gestational age (<14 or ≥14 weeks) to receive: (1) usual care (UC) for stop smoking support or (2) UC plus an intervention to increase adherence to NRT, called 'Baby, Me and NRT' (BMN), comprising adherence counselling, automated tailored text messages, a leaflet and website. The primary outcome is biochemically validated smoking abstinence at or around childbirth, measured from 36 weeks gestation. Secondary outcomes include NRT adherence, other smoking measures and birth outcomes. Questionnaires collect follow-up data augmented by medical record information. We anticipate quit rates of 10% and 16% in the control and intervention groups, respectively (risk ratio=1.6). By recruiting 1320 participants, the trial should have 90% power (alpha=5%) to detect this intervention effect. An economic analysis will use the Economics of Smoking in Pregnancy model to determine cost-effectiveness. ETHICS AND DISSEMINATION: Ethics approval was granted by Bloomsbury National Health Service's Research Ethics Committee (21/LO/0123). Written informed consent will be obtained from all participants. Findings will be disseminated to the public, funders, relevant practice/policy representatives, researchers and participants. TRIAL REGISTRATION NUMBER: ISRCTN16830506. PROTOCOL VERSION: 5.0, 10 Oct 2023.

Advice only versus advice and a physiotherapy programme for acute traumatic anterior shoulder dislocation: the ARTISAN RCT.

Background: The extra benefit of a programme of physiotherapy in addition to advice alone, following first-time traumatic shoulder dislocation, is uncertain. We compared the clinical and cost-effectiveness of a single session of advice with a single session of advice and a programme of physiotherapy. Objective: The primary objective was to quantify and draw inferences about observed differences in the Oxford Shoulder Instability Score between the trial treatment groups 6 months post randomisation, in adults with a first-time traumatic shoulder dislocation. Design: A pragmatic, multicentre, superiority, randomised controlled trial with embedded qualitative study. Setting: Forty-one hospitals in the UK NHS. Participants: Adults with a radiologically confirmed first-time traumatic anterior shoulder dislocation, being managed non-operatively. People with neurovascular complications or bilateral dislocations, and those unable to adhere to trial procedures or unable to attend physiotherapy within 6 weeks of injury, or who had previously been randomised, were excluded. Interventions: All participants received the same initial shoulder examination followed by advice to aid self-management, lasting up to 1 hour and administered by a physiotherapist (control). Participants randomised to receive an additional programme of physiotherapy were offered sessions lasting for up to 30 minutes, over a maximum duration of 4 months from the date of randomisation (intervention). Main outcome measures: The primary outcome measure was the Oxford Shoulder Instability Score. This is a self-completed outcome measure containing 12 questions (0-4 points each), with possible scores from 0 (worst function) to 48 (best function). Measurements were collected at 6 weeks, 3 months, 6 months and 12 months by postal questionnaire; 6 months was the primary outcome time point. The primary health outcome for economic evaluation was the quality-adjusted life-year, in accordance with National Institute of Health and Care Excellence guidelines. Results: Between 14 November 2018 and 14 March 2022, 482 participants were randomised to advice (n = 240) or advice and a programme of physiotherapy (n = 242). Participants were 34% female, with a mean age of 45 years, and treatment arms were balanced at baseline. There was not a statistically significant difference in the primary outcome between advice only and advice plus a programme of physiotherapy at 6 months for the primary intention-to-treat adjusted analysis (favours physiotherapy: 1.5, 95% confidence interval -0.3 to 3.5) or at earlier 3-month and 6-week time points on the Oxford Shoulder Instability Score (0-48; higher scores indicate better function). The probability of physiotherapy being cost-effective at a willingness-to-pay threshold of £30,000 was 0.95. Conclusions: We found little difference in the primary outcome or other secondary outcomes. Advice with additional physiotherapy sessions was found likely to be cost-effective. However, small imprecise incremental costs and quality-adjusted life-years raise questions on whether it is the best use of scarce physiotherapy resources given current service demands. Limitations: Loss to follow-up was 27%; however, the observed standard deviation was much smaller than anticipated. These changes in parameters reduced the number of participants required to observe the planned target difference of four points. Our post hoc sensitivity analysis, accounting for missing data, gives similar results. Future work: Further research should be directed towards optimising self-management strategies. Study registration: This study is registered as ISRCTN63184243. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/167/56) and is published in full in Health Technology Assessment; Vol. 28, No. 22. See the NIHR Funding and Awards website for further award information.

The shoulder dislocates (comes out of its socket joint) when the upper end of the arm bone is forced out during an injury. This common problem occurs mostly in men in their 20s and women aged over 80. After the bone is put back in its socket, most people are managed with physiotherapy. In the United Kingdom, once the bone is back in its socket, there is a range of physiotherapy provision: some hospitals offer advice, and some offer advice and a course of additional physiotherapy sessions. We compared advice alone to advice and physiotherapy for people who had a shoulder that had come out of its joint for the first time. Physiotherapy advice and additional sessions included education about the injury and exercises to move and strengthen the shoulder. When we started this project, this was the first time these two treatments had been compared. Our aim was to compare what activities the two groups could do 6 months after injury via a questionnaire. We also compared quality of life and the cost of rehabilitation at 6 weeks, 3 months, 6 months and 12 months after injury. Adults with a shoulder out of its joint and who were not having surgery were asked to take part. All adults who were eligible and consented to take part were assigned, by chance, to either a single session of advice or the same session followed by physiotherapy. Between 14 November 2018 and 14 March 2022 we collected data on 482 people, from 41 NHS sites across the UK. We found at 6 months there was little evidence that additional physiotherapy was better, when compared to advice alone. Cost-effectiveness analysis (comparing changes in costs and quality of life) suggests additional physiotherapy might provide value for money. However, the changes involved are small and uncertain.

Enhancing Pragmatic Language skills for Young children with Social communication difficulties (E-PLAYS-2) trial: study protocol for a cluster-randomised controlled trial evaluating a computerised intervention to promote communicative development and collaborative skills in young children.

BACKGROUND: A number of children experience difficulties with social communication and this has long-term deleterious effects on their mental health, social development and education. The E-PLAYS-2 study will test an intervention ('E-PLAYS') aimed at supporting such children. E-PLAYS uses a dyadic computer game to develop collaborative and communication skills. Preliminary studies by the authors show that E-PLAYS can produce improvements in children with social communication difficulties on communication test scores and observed collaborative behaviours. The study described here is a definitive trial to test the effectiveness and cost-effectiveness of E-PLAYS delivered by teaching assistants in schools. METHODS: The aim of the E-PLAYS-2 trial is to establish the effectiveness and cost-effectiveness of care as usual plus the E-PLAYS programme, delivered in primary schools, compared to care as usual. Cluster-randomisation will take place at school level to avoid contamination. The E-PLAYS intervention will be delivered by schools' teaching assistants. Teachers will select suitable children (ages 5-7 years old) from their schools using guidelines provided by the research team. Assessments will include blinded language measures and observations (conducted by the research team), non-blinded teacher-reported measures of peer relations and classroom behaviour and parent-reported use of resources and quality of life. A process evaluation will also include interviews with parents, children and teaching assistants, observations of intervention delivery and a survey of care as usual. The primary analysis will compare pragmatic language scores for children who received the E-PLAYS intervention versus those who did not at 40 weeks post-randomisation. Secondary analyses will assess cost-effectiveness and a mixed methods process evaluation will provide richer data on the delivery of E-PLAYS. DISCUSSION: The aim of this study is to undertake a final, definitive test of the effectiveness of E-PLAYS when delivered by teaching assistants within schools. The use of technology in game form is a novel approach in an area where there are currently few available interventions. Should E-PLAYS prove to be effective at the end of this trial, we believe it is likely to be welcomed by schools, parents and children. TRIAL REGISTRATION: ISRCTN 17561417, registration date 19th December 2022. PROTOCOL VERSION: v1.1 19th June 2023.

Examining the effectiveness of the Gateway conditional caution on health and well-being of young adults committing low-level offences: a randomised controlled trial.

BACKGROUND: Young adults who commit low-level offences commonly have a range of health and social needs and are significantly over-represented in the criminal justice system. These young adults may need to attend court and potentially receive penalties including imprisonment. Alternative routes exist, which can help address the underlying causes of offending. Some feel more should be done to help young adults entering the criminal justice system. The Gateway programme was a type of out-of-court disposal developed by Hampshire Constabulary, which aimed to address the complex needs of young adults who commit low-level crimes. This study aimed to evaluate the effectiveness and cost-effectiveness of the Gateway programme, issued as a conditional caution, compared with usual process. METHODS: The Gateway study was a pragmatic, parallel-group, superiority randomised controlled trial that recruited young adults who had committed a low-level offence from four sites covering Hampshire and Isle of Wight. The primary outcome was mental health and well-being measured using the Warwick-Edinburgh Mental Well-being Scale. Secondary outcomes were quality of life, alcohol and drug use, and recidivism. Outcomes were measured at 4, 16 and 52 weeks postrandomisation. RESULTS: Due to issues with retention of participants and low data collection rates, recruitment ended early, with 191 eligible participants randomised (Gateway 109; usual process 82). The primary outcome was obtained for 93 (48.7%) participants at 4 weeks, 93 (48.7%) at 16 weeks and 43 (22.5%) at 1 year. The high attrition rates meant that effectiveness could not be assessed as planned. CONCLUSIONS: Gateway is the first trial in a UK police setting to have a health-related primary outcome requiring individual data collection, rather than focusing solely on recidivism. We demonstrated that it is possible to recruit and randomise from the study population, however follow-up rates were low. Further work is needed to identify ways to facilitate engagement between researchers and vulnerable populations to collect data. TRIAL REGISTRATION NUMBER: ISRCTN11888938.

Surgical versus non-surgical management of lateral compression type-1 pelvic fracture in adults 60 years and older: the L1FE RCT.

Background: Lateral compression type-1 pelvic fractures are a common fragility fracture in older adults. Patients who do not mobilise due to ongoing pain are at greater risk of immobility-related complications. Standard treatment in the United Kingdom is provision of pain relief and early mobilisation, unlike fragility hip fractures, which are usually treated surgically based on evidence that early surgery is associated with better outcomes. Currently there is no evidence on whether patients with lateral compression type-1 fragility fractures would have a better recovery with surgery than non-surgical management. Objectives: To assess the clinical and cost effectiveness of surgical fixation with internal fixation device compared to non-surgical management of lateral compression type-1 fragility fractures in older adults. Design: Pragmatic, randomised controlled superiority trial, with 12-month internal pilot; target sample size was 600 participants. Participants were randomised between surgical and non-surgical management (1 : 1 allocation ratio). An economic evaluation was planned. Setting: UK Major Trauma Centres. Participants: Patients aged 60 years or older with a lateral compression type-1 pelvic fracture, arising from a low-energy fall and unable to mobilise independently to a distance of 3 m and back due to pelvic pain 72 hours after injury. Interventions: Internal fixation device surgical fixation and non-surgical management. Participants, surgeons and outcome assessors were not blinded to treatment allocation. Main outcome measures: Primary outcome - average patient health-related quality of life, over 6 months, assessed by the EuroQol-5 Dimensions, five-level version utility score. Secondary outcomes (over the 6 months following injury) - self-rated health, physical function, mental health, pain, delirium, displacement of pelvis, mortality, complications and adverse events, and resource use data for the economic evaluation. Results: The trial closed early, at the end of the internal pilot, due to low recruitment. The internal pilot was undertaken in two separate phases because of a pause in recruitment due to the coronavirus disease 2019 pandemic. The planned statistical and health economic analyses were not conducted. Outcome data were summarised descriptively. Eleven sites opened for recruitment for a combined total of 92 months. Three-hundred and sixteen patients were assessed for eligibility, of whom 43 were eligible (13.6%). The main reason for ineligibility was that the patient was able to mobilise independently to 3 m and back (n = 161). Of the 43 eligible participants, 36 (83.7%) were approached for consent, of whom 11 (30.6%) provided consent. The most common reason for eligible patients not consenting to take part was that they were unwilling to be randomised to a treatment (n = 10). There were 11 participants, 5 randomised to surgical management with internal fixation device and 6 to non-surgical management. The average age of participants was 83.0 years (interquartile range 76.0, 89.0) and the EuroQol-5 Dimensions, five-level version utility score at 6 months post randomisation (n = 8) was 0.32 (standard deviation 0.37). A limitation of the trial was that study objectives were not addressed due to poor recruitment. Conclusions: It was not feasible to recruit to this trial in the current context. Further research to understand the treatment and recovery pathways of this group of patients, along with their outcomes, would be needed prior to undertaking a future trial. Future work: Exploration of equipoise across different healthcare professional groups. Investigate longer-term patient outcomes. Trial registration: This trial is registered as ISRCTN16478561. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/167/57) and is published in full in Health Technology Assessment; Vol. 28, No. 15. See the NIHR Funding and Awards website for further award information.

When older adults with weak bones fall onto their side, they can fracture the pelvis in a certain way known as a 'lateral compression type-1 fracture'; this summary will use 'pelvic fracture'. Pelvic fractures can heal without surgery; patients are offered pain relief and encouraged to move as much as they can after the injury. Pelvic fractures can be painful, and some people are not able to get up and walk for weeks. These fractures can cause health problems such as chest infections, urinary tract infections, pressure sores and blood clots. To avoid these problems, we are trying to find treatments to help people recover sooner. Pelvic surgeons think patients may benefit from surgery with an internal fixation device (a bar and screws) to stabilise the pelvis; however, there can be risks and complications with any surgery. This study aimed to find out which treatment is better for patients and better value for money for the National Health Service. This required 600 people aged over 60, in hospital with a pelvic fracture and having difficulty walking to take part. Three hundred would receive surgery and 300 would receive non-surgical treatment. Over 6 months, participants would complete questionnaires, a walking assessment and have X-rays to check healing. The trial had a 12-month run-in period to see if enough people would take part. The trial closed early as we were unable to recruit sufficient people into the study. Fewer older patients with pelvic fractures were identified than expected, 51% were able to walk after a few days and therefore were not eligible to be included in the study. Of the patients, 13.6% were eligible and 30.6% of those consented to take part. Restrictions on visitors during the coronavirus disease 2019 pandemic made it difficult to discuss the study with patients' families and fewer patients were admitted to hospital where the study was taking place. The research question could not be answered by this study at the present time.

Can routine assessment of older people's mental health lead to improved outcomes: A regression discontinuity analysis.

OBJECTIVE: To assess whether case finding for depression among people aged 65 and above improves mental health. DESIGN: Opportunistic evaluation using a regression discontinuity analysis with data from a randomised controlled trial. SETTING: The REFORM trial, a falls prevention study that recruited patients from NHS podiatry clinics. PARTICIPANTS: 1010 community-dwelling adults over the age of 65 with at least one risk factor for falling (recent previous fall or fear of falling). INTERVENTION: Letter sent to patient's General Practitioner if they scored 10 points or above on the 15-item Geriatric Depression Scale (GDS-15) informing them of the patient's risk of depression. MAIN OUTCOME MEASURE: GDS-15 score six months after initial completion of GDS-15. RESULTS: 895 (88.6%) of the 1010 participants randomised into REFORM had a valid baseline and six-month GDS-15 score and were included in this study. The mean GDS-15 baseline score was 3.5 (SD 3.0, median 3.0, range 0-15); 639 (71.4%) scored 0-4, 204 (22.8%) scored 5-9 indicating mild depression, and 52 (5.8%) scored 10 or higher indicating severe depression. At six months follow-up, those scoring 10 points or higher at baseline had, on average, a reduction of 1.08 points on the GDS-15 scale (95% confidence interval -1.83 to -0.33, p = 0.005) compared to those scoring less than 10, using the simplest linear regression model. CONCLUSION: Case finding of depression in podiatry patients based on a GDS-15 score of 10 or more followed by a letter to their General Practitioner significantly reduced depression severity. Whether this applies to all older patients in primary care is unknown. Further research is required to confirm these findings. Regression discontinuity analyses could be prespecified and embedded within other existing research studies.

Undertaking Studies Within A Trial to evaluate recruitment and retention strategies for randomised controlled trials: lessons learnt from the PROMETHEUS research programme.

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.

A Study Within A Trial is a research study nested inside a larger 'host trial', promoting the use of Studies Within A Trial aimed to do Study Within A Trial routine practice in clinical trial units by funding and supporting at least 25 Studies Within A Trial. The best way to test health and social care treatments is to do a randomised controlled trial ('trial'), where some patients get the treatment being tested and some do not. The results of different groups are compared to see if the treatment improves care. Recruiting patients and keeping them involved in trials is often very difficult. Research teams often do not know how best to recruit and keep patients engaged as the methods have not been tested to see if they work. The best way to test these methods is by doing a Study Within A Trial. We test a programme of Studies Within A Trial for recruiting and keeping patients engaged in trials. Trial teams were able to apply for funding of up to £5000 and receive support from Promoting the use of Study Within A Trial team to do Studies Within A Trial. We used our experience of doing Studies Within A Trial to outline lessons learnt for doing Studies Within A Trial. We funded 42 Studies Within A Trial and gave teams necessary advice to do them. We significantly increased the knowledge for both recruitment and retention strategies, and found 'pre-notifying' before sending questionnaires, sending pens and personalised text messages were all effective for increasing responses by participants. We tested Studies Within A Trial across several different trials at the same time to find out more quickly whether their methods worked. We highlight key lessons learnt to guide others doing Studies Within A Trial, including involving patient partners; picking the right strategy to test; getting ethical approvals; how to do and report Studies Within A Trial. Promoting the use of studies within a trial was successful and supported more Studies Within A Trial than planned. We hope our experience will support those doing Studies Within A Trial in the future.

Behaviour change intervention for toothbrushing (lesson and text messages) to prevent dental caries in secondary school pupils: The BRIGHT randomized control trial.

OBJECTIVES: This multicentre, assessor-blinded, two-arm cluster randomized trial evaluated the clinical and cost-effectiveness of a behaviour change intervention promoting toothbrushing for preventing dental caries in UK secondary schools. METHODS: Pupils aged 11-13 years with their own mobile telephone attending secondary schools with above average free school meals eligibility were randomized (at year-group level) to receive a lesson and twice-daily text messages or to usual care. Year-groups (n = 84) from 42 schools including 4680 pupils (intervention, n = 2262; control, n = 2418) were randomized. RESULTS: In 2383 participants with valid data at baseline and 2.5 years, the primary outcome of presence of at least one treated or untreated carious lesion (D4-6 MFT [Decayed, Missing and Filled Teeth] in permanent teeth using International Caries Detection and Assessment System) was 44.6% in the intervention group and 43.0% in control (odds ratio [OR] 1.04, 95% CI 0.85-1.26, p = .72). There were no statistically significant differences in secondary outcomes of presence of at least one treated or untreated carious lesion (D1-6 MFT), number of D4-6 MFT and D1-6 MFT, plaque and bleeding scores or health-related- (Child Health Utility 9D) or oral health-related- quality of life (CARIES-QC). However, twice-daily toothbrushing, reported by 77.6% of pupils at baseline, increased at 6 months (intervention, 86.9%; control, 83.0%; OR 1.30, 95% CI 1.03-1.63, p = .03), but returned to no difference at 2.5 years (intervention, 81.0%; control, 79.9%; OR 1.05, 95% CI 0.84-1.30, p = .69). Estimated incremental costs and quality-adjusted life-years (QALYs) of the intervention, relative to control, were £1.02 (95% CI -1.29 to 3.23) and -0.003 (95% CI -0.009 to 0.002), respectively, with a 7% chance of being cost-effective (£20 000/QALY gained threshold). CONCLUSION: There was no evidence of statistically significant difference for caries prevalence at 2.5-years. The intervention's positive 6-month toothbrushing behaviour change did not translate into caries reduction. (ISRCTN 12139369). COVID-19 pandemic adversly affected follow-up.

Acute rehabilitation following traumatic anterior shoulder dislocation (ARTISAN): pragmatic, multicentre, randomised controlled trial.

OBJECTIVE: To assess the effects of an additional programme of physiotherapy in adults with a first-time traumatic shoulder dislocation compared with single session of advice, supporting materials, and option to self-refer to physiotherapy. DESIGN: Pragmatic, multicentre, randomised controlled trial (ARTISAN). SETTING AND PARTICIPANTS: Trauma research teams at 41 UK NHS Trust sites screened adults with a first time traumatic anterior shoulder dislocation confirmed radiologically, being managed non-operatively. People were excluded if they presented with both shoulders dislocated, had a neurovascular complication, or were considered for surgical management. INTERVENTIONS: One session of advice, supporting materials, and option to self-refer to physiotherapy (n=240) was assessed against the same advice and supporting materials and an additional programme of physiotherapy (n=242). Analyses were on an intention-to-treat basis with secondary per protocol analyses. MAIN OUTCOME MEASURES: The primary outcome was the Oxford shoulder instability score (a single composite measure of shoulder function), measured six months after treatment allocation. Secondary outcomes included the QuickDASH, EQ-5D-5L, and complications. RESULTS: 482 participants were recruited from 40 sites in the UK. 354 (73%) participants completed the primary outcome score (n=180 allocated to advice only, n=174 allocated to advice and physiotherapy). Participants were mostly male (66%), with a mean age of 45 years. No significant difference was noted between advice compared with advice and a programme of physiotherapy at six months for the primary intention-to-treat adjusted analysis (between group difference favouring physiotherapy 1.5 (95% confidence interval -0.3 to 3.5)) or at earlier three month and six week timepoints. Complication profiles were similar across the two groups (P>0.05). CONCLUSIONS: An additional programme of current physiotherapy is not superior to advice, supporting materials, and the option to self-refer to physiotherapy. TRIAL REGISTRATION: Current Controlled Trials ISRCTN63184243.

Bathing Adaptations in the Homes of Older Adults (BATH-OUT-2): study protocol for a randomised controlled trial, economic evaluation and process evaluation.

BACKGROUND: The onset of disability in bathing is particularly important for older adults as it can be rapidly followed by disability in other daily activities; this may represent a judicious time point for intervention in order to improve health, well-being and associated quality of life. An important environmental and preventative intervention is housing adaptation, but there are often lengthy waiting times for statutory provision. In this randomised controlled trial (RCT), we aim to evaluate the effectiveness and cost-effectiveness of bathing adaptations compared to no adaptations and to explore the factors associated with routine and expedited implementation of bathing adaptations. METHODS: BATH-OUT-2 is a multicentre, two-arm, parallel-group RCT. Adults aged 60 and over who are referred to their local authority for an accessible level access shower will be randomised, using pairwise randomisation, 1:1, to receive either an expedited provision of an accessible shower via the local authority or a usual care control waiting list. Participants will be followed up for a maximum of 12 months and will receive up to four follow-ups in this duration. The primary outcome will be the participant's physical well-being, assessed by the Physical Component Summary score of the Short Form-36 (SF-36), 4 weeks after the intervention group receives the accessible shower. The secondary outcomes include the Mental Component Summary score of the SF-36, self-reported falls, health and social care resource use, health-related quality of life (EQ-5D-5L), social care-related quality of life (Adult Social Care Outcomes Toolkit (ASCOT)), fear of falling (Short Falls Efficacy Scale), independence in bathing (Barthel Index bathing question), independence in daily activities (Barthel Index) and perceived difficulty in bathing (0-100 scale). A mixed-methods process evaluation will comprise interviews with stakeholders and a survey of local authorities with social care responsibilities in England. DISCUSSION: The BATH-OUT-2 trial is designed so that the findings will inform future decisions regarding the provision of bathing adaptations for older adults. This trial has the potential to highlight, and then reduce, health inequalities associated with waiting times for bathing adaptations and to influence policies for older adults. TRIAL REGISTRATION: ISRCTN Registry ISRCTN48563324. Prospectively registered on 09/04/2021.

Can we achieve better trial recruitment by presenting patient information through multimedia? Meta-analysis of 'studies within a trial' (SWATs).

BACKGROUND: People need high-quality information to make decisions about research participation. Providing information in written format alone is conventional but may not be the most effective and acceptable approach. We developed a structure for the presentation of information using multimedia which included generic and trial-specific content. Our aim was to embed 'Studies Within A Trial' (SWATs) across multiple ongoing trials to test whether multimedia presentation of patient information led to better rates of recruitment. METHODS: Five trials included a SWAT and randomised their participants to receive a multimedia presentation alongside standard information, or standard written information alone. We collected data on trial recruitment, acceptance and retention and analysed the pooled results using random effects meta-analysis, with the primary outcome defined as the proportion of participants randomised following an invitation to take part. RESULTS: Five SWATs provided data on the primary outcome of proportion of participants randomised. Multimedia alongside written information results in little or no difference in recruitment rates (pooled odds ratio = 0.96, 95% CI: 0.79 to 1.17, p-value = 0.671, I2 = 0%). There was no effect on any other outcomes. CONCLUSIONS: Multimedia alongside written information did not improve trial recruitment rates. TRIAL REGISTRATION: ISRCTN71952900, ISRCTN 06710391, ISRCTN 17160087, ISRCTN05926847, ISRCTN62869767.

The CALM trial protocol: a randomised controlled trial of a guided self-help cognitive behavioural therapy intervention to reduce dental anxiety in children.

BACKGROUND: Globally, around 13% of children experience dental anxiety (DA). This group of patients frequently miss dental appointments, have greater reliance on treatment under general anaesthesia (GA) and have poorer oral health-related quality of life (OHRQoL) than their non-dentally anxious peers. Recently, a low-intensity cognitive behavioural therapy (CBT)-based, self-help approach has been recommended for management of childhood anxiety disorders. A feasibility study conducted in secondary care found this guided self-help CBT resource reduced DA and a randomised controlled trial was recommended. The present study aims to establish the clinical and cost-effectiveness of a guided self-help CBT intervention to reduce DA in children attending primary dental care sites compared to usual care. METHODS: This 4-year randomised controlled trial will involve 600 children (aged 9-16 years) and their parent/carers in 30 UK primary dental care sites. At least two dental professionals will participate in each site. They will be assigned, using random allocation, to receive the CBT training and deliver the intervention or to deliver usual care. Children with DA attending these sites, in need of treatment, will be randomly allocated to be treated either by the intervention (CBT) or control (usual care) dental professional. Children will complete questionnaires relating to DA, OHRQoL and HRQoL before treatment, immediately after treatment completion and 12 months post-randomisation. Attendance, need for sedation/GA and costs of the two different approaches will be compared. The primary outcome, DA, will be measured using the Modified Child Dental Anxiety Scale. Scores will be compared between groups using a linear mixed model. DISCUSSION: Treating dentally anxious patients can be challenging and costly. Consequently, these children are frequently referred to specialist services for pharmacological interventions. Longer waiting times and greater travel distances may then compound existing healthcare inequalities. This research will investigate whether the intervention has the potential to reduce DA and improve oral health outcomes in children over their life-course, as well as upskilling primary dental healthcare professionals to better manage this patient group. TRIAL REGISTRATION: This clinical trial has been registered with an international registry and has been allocated an International Standard Randomised Controlled Trial Number (ISRCTN27579420).

Set up and assessment of progression criteria for internal pilots: the Brushing RemInder 4 Good oral HealTh (BRIGHT) trial example.

BACKGROUND: Dental caries is common in young people and has wide-ranging ramifications for health and quality of life. Text messaging interventions show promise as a means to promote oral health behaviour change among young people. This paper reports the internal pilot of the Brushing RemInder 4 Good oral HealTh (BRIGHT) trial, which is evaluating an intervention comprising an oral health classroom lesson and text messages about toothbrushing, on caries in young people. Pilot trial objectives were to evaluate the feasibility and appropriateness of recruitment and data collection methods, the randomisation strategy, and intervention delivery against progression criteria for the main trial. METHODS: This is an internal pilot trial embedded within an assessor-blinded, two-arm, cluster randomised controlled trial. Participants were pupils aged 11-13 years (in year 7/S1 or year 8/S2) in secondary schools in England, Scotland, and Wales with above average pupil eligibility for free school meals. Following completion of pupil baseline questionnaires and dental assessments, year groups within schools were randomised to the intervention or control arm. Approximately 12 weeks later, participants completed a follow-up questionnaire, which included questions about sources of oral health advice to assess intervention contamination between year groups. At the end of the pilot phase, trial conduct was reviewed against pre-specified progression criteria. RESULTS: Ten schools were recruited for the pilot, with 20 year groups and 1073 pupils randomised (average of 54 pupils per year group). Data collection methods and intervention delivery were considered feasible, the response rate to the follow-up questionnaire was over 80%, there was an indication of a positive effect on self-reported toothbrushing, and interest was obtained from 80% of the schools required for the main trial. Despite partial intervention contamination between year groups, within-school randomisation at the level of the year-group was considered appropriate for the main trial, and the sample size was revised to account for partial contamination. Facilitators and barriers to recruitment and data collection were identified and strategies refined for the main trial. CONCLUSIONS: Progression to the main trial of BRIGHT, with some design refinements, was concluded. The internal pilot was an efficient way to determine trial feasibility and optimise trial processes. TRIAL REGISTRATION: ISRCTN registry, ISRCTN12139369 , registered 10/05/2017.

Effect of financial voucher incentives provided with UK stop smoking services on the cessation of smoking in pregnant women (CPIT III): pragmatic, multicentre, single blinded, phase 3, randomised controlled trial.

OBJECTIVE: To examine effectiveness, cost effectiveness, generalisability, and acceptability of financial incentives for smoking cessation during pregnancy in addition to variously organised UK stop smoking services. DESIGN: Pragmatic, multicentre, single blinded, phase 3, randomised controlled trial (Cessation in Pregnancy Incentives Trial phase 3 (CPIT III)). SETTING: Seven UK stop smoking services provided in primary and secondary care facilities in Scotland, Northern Ireland, and England. PARTICIPANTS: 944 pregnant women (age ≥16 years) who self-reported as being smokers (at least one cigarette in the past week) when asked at first maternity visit, less than 24 weeks' gestation, and notified to the trial team by routine stop smoking services. INTERVENTIONS: Participants in the control group were offered the standard stop smoking services, which includes the offer of counselling by specially trained workers using withdrawal orientated therapy and the offer of free nicotine replacement therapy. The intervention was the offer of usual support from the stop smoking services and the addition of up to £400 ($440; €455) of LoveToShop financial voucher incentives for engaging with current stop smoking services or to stop smoking, or both, during pregnancy. MAIN OUTCOME MEASURES: Self-reported smoking cessation in late pregnancy (between 34 and 38 weeks' gestation) corroborated by saliva cotinine (and anabasine if using nicotine replacement products). Results were adjusted for age, smoking years, index of multiple deprivation, Fagerström score, before or after covid, and recruitment site. Secondary outcomes included point and continuous abstinence six months after expected date of delivery, engagement with stop smoking services, biochemically validated abstinence from smoking at four weeks after stop smoking date, birth weight of baby, cost effectiveness, generalisability documenting formats of stop smoking services, and acceptability to pregnant women and their carers. RESULTS: From 9 January 2018 to 4 April 2020, of 4032 women screened by stop smoking services, 944 people were randomly assigned to the intervention group (n=471) or the control group (n=470). Three people asked for their data to be removed. 126 (27%) of 471 participants stopped smoking from the intervention group and 58 (12%) of 470 from the control group (adjusted odds ratio 2.78 (1.94 to 3.97) P<0.001). Serious adverse events were miscarriages and other expected pregnancy events requiring hospital admission; all serious adverse events were unrelated to the intervention. Most people who stopped smoking from both groups relapsed after their baby was born. CONCLUSIONS: The offer of up to £400 of financial voucher incentives to stop smoking during pregnancy as an addition to current UK stop smoking services is highly effective. This bolt-on intervention supports new guidance from the UK National Institute for Health and Care Excellence, which includes the addition of financial incentives to support pregnant women to stop smoking. Continuing incentives to 12 months after birth is being examined to prevent relapse. TRIAL REGISTRATION: ISRCTN Registry ISRCTN15236311.

Recruitment patterns in multicentre randomised trials fit more closely to Price's Law than the Pareto Principle: A review of trials funded and published by the United Kingdom Health Technology Assessment Programme.

OBJECTIVE: This review investigates whether the distribution of recruitment to multicentre randomised controlled trials (RCTs) fits the "Pareto Principle", i.e. 80% of participants are recruited by 20% of sites, or Price's Law, i.e. 50% of participants are recruited by the square root of the total number of sites. METHODS: A review of HTA reports published between 2017 and 2019. RESULTS: 40 RCTs conducted face-to-face recruitment, five recruited via mail-outs and one used both methods. For face-to-face recruitment (n = 41 studies), 80% of participants were recruited by the top recruiting 42.6% of sites; for mail-out methods (n = 6 studies) this was 52.0%. From the square root of sites, 51.3% and 31.8% of participants were recruited for the two recruitment approaches, respectively. Specifically, 3 (7.3%, 95% CI 2.5% to 19.4%) and 20 (48.8%, 95% CI 34.3% to 63.5%) RCTs that recruited face-to-face followed Pareto Principle and Price's Law, respectively. One mail-out recruitment study followed one of these principles, Price's Law. Chief Investigator (CI) sites (n = 24) in face-to-face recruitment studies recruited 18.1% of participants. CONCLUSION: Face-to-face recruitment to HTA-funded RCTs fits more closely to Price's Law than the Pareto Principle, with the CI's site recruiting nearly a fifth of participants. Since we focussed on HTA-funded RCTs with ≥9 recruiting sites and for which the recruitment method and number recruited by site were known, our findings are limited in their generalisability. However, this trend could be used as a guide to aid in estimating how many sites RCTs need. More accurate estimation may prevent the need for recruitment extensions.

Cost-effectiveness of hydroxychloroquine versus placebo for hand osteoarthritis: economic evaluation of the HERO trial.

Background: An economic evaluation alongside the Hydroxychloroquine Effectiveness in Reducing symptoms of hand Osteoarthritis (HERO) trial was undertaken to assess the cost-effectiveness of hydroxychloroquine compared with placebo for symptomatic treatment of hand osteoarthritis for patients with at least moderate hand pain and inadequate response to current therapies. Methods: A trial-based cost-utility analysis was undertaken from the perspective of the UK National Health Service and Personal Social Services over a 12-month time horizon, using evidence from 248 participants included in the HERO trial, conducted in England. Patient-level data were collected prospectively over a 12-month period, using participant-completed questionnaires and investigator forms, to collect healthcare utilisation, costs and quality-adjusted life years (QALYs) using the EQ-5D-5L. The base-case analysis was conducted on an intention-to-treat basis and used multiple imputation methods to deal with missing data. Results were presented in terms of incremental cost-effectiveness ratios (incremental cost per QALY) and net health benefit, with uncertainty surrounding the findings explored using cost-effectiveness acceptability curves. Results: The base-case analysis estimated slightly lower costs on average (-£11.80; 95% confidence interval (CI) -£15.60 to -£8.00) and marginally fewer QALYs (-0.0052; 95% CI -0.0057 to -0.0047) for participants in the hydroxychloroquine group versus placebo group at 12 months. The resulting incremental cost-effectiveness ratio of £2,267 per QALY lost indicated that although costs were saved, health-related quality of life was lost. Even assuming symmetrical preferences regarding losses and gains for health benefits, the findings do not fall within the cost-effective region. Similar findings arose for analyses conducted from the societal perspective and using complete cases only. Conclusions: This economic evaluation indicates that hydroxychloroquine is unlikely to provide a cost-effective pain relief option for improving health-related quality of life in adult patients with moderate-to-severe hand osteoarthritis.

Surgery versus conservative management of stable thoracolumbar fracture: the PRESTO feasibility RCT.

BACKGROUND: There is informal consensus that simple compression fractures of the body of the thoracolumbar vertebrae between the 10th thoracic vertebra and the second lumbar vertebra without neurological complications can be managed conservatively and that obvious unstable fractures require surgical fixation. However, there is a zone of uncertainty about whether surgical or conservative management is best for stable fractures. OBJECTIVES: To assess the feasibility of a definitive randomised controlled trial comparing surgical fixation with initial conservative management of stable thoracolumbar fractures without spinal cord injury. DESIGN: External randomised feasibility study, qualitative study and national survey. SETTING: Three NHS hospitals. METHODS: A feasibility randomised controlled trial using block randomisation, stratified by centre and type of injury (high- or low-energy trauma) to allocate participants 1 : 1 to surgery or conservative treatment; a costing analysis; a national survey of spine surgeons; and a qualitative study with clinicians, recruiting staff and patients. PARTICIPANTS: Adults aged ≥ 16 years with a high- or low-energy fracture of the body of a thoracolumbar vertebra between the 10th thoracic vertebra and the second lumbar vertebra, confirmed by radiography, computerised tomography or magnetic resonance imaging, with at least one of the following: kyphotic angle > 20° on weight-bearing radiographs or > 15° on a supine radiograph or on computerised tomography; reduction in vertebral body height of 25%; a fracture line propagating through the posterior wall of the vertebra; involvement of two contiguous vertebrae; or injury to the posterior longitudinal ligament or annulus in addition to the body fracture. INTERVENTIONS: Surgical fixation: open spinal surgery (with or without spinal fusion) or minimally invasive stabilisation surgery. Conservative management: mobilisation with or without a brace. MAIN OUTCOME MEASURE: Recruitment rate (proportion of eligible participants randomised). RESULTS: Twelve patients were randomised (surgery, n = 8; conservative, n = 4). The proportion of eligible patients recruited was 0.43 (95% confidence interval 0.24 to 0.63) over a combined total of 30.7 recruitment months. Of 211 patients screened, 28 (13.3%) fulfilled the eligibility criteria. Patients in the qualitative study (n = 5) expressed strong preferences for surgical treatment, and identified provision of information about treatment and recovery and when and how they are approached for consent as important. Nineteen surgeons and site staff participated in the qualitative study. Key themes were the lack of clinical consensus regarding the implementation of the eligibility criteria in practice and what constitutes a stable fracture, alongside lack of equipoise regarding treatment. Based on the feasibility study eligibility criteria, 77% (50/65) and 70% (46/66) of surgeons participating in the survey were willing to randomise for high- and low-energy fractures, respectively. LIMITATIONS: Owing to the small number of participants, there is substantial uncertainty around the recruitment rate. CONCLUSIONS: A definitive trial is unlikely to be feasible currently, mainly because of the small number of patients meeting the eligibility criteria. The recruitment and follow-up rates were slightly lower than anticipated; however, there is room to increase these based on information gathered and the support within the surgical community for a future trial. FUTURE WORK: Development of consensus regarding the population of interest for a trial. TRIAL REGISTRATION: Current Controlled Trials ISRCTN12094890. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 62. See the NIHR Journals Library website for further project information.

Fractures occurring in the mid- to low back region (or thoracolumbar fractures) are the most common back fractures. When the fracture is stable with no spinal nerve injury, there is uncertainty whether treatment with surgery or non-surgical treatment (e.g. stabilising the spine with a brace) results in the best outcome for patients. The Pragmatic Randomised Evaluation of Stable Thoracolumbar fracture treatment Outcomes (PRESTO) study aimed to explore whether or not it would be feasible to carry out a full-scale study to find out which of these two treatments works best. Adults aged ≥ 16 years being treated for these fractures in three hospitals were invited to take part in the study. Over the course of 1 year, we assessed how many patients were treated, the number who met the study entry criteria and the proportion of eligible patients who agreed to take part. Staff and patients were interviewed about the study processes and their experiences of taking part. Spine surgeons from around the UK were also asked to complete an online survey, which asked questions about the treatment of patients with this fracture. There were fewer patients than expected who met the study entry criteria and, of these, fewer patients who agreed to take part. There were differences among surgeons about the definition of a stable fracture, and we found that surgeons have strong views about whether or not surgery is appropriate when fractures are stable. We also found that more support would be required for the staff involved in inviting patients to take part in a bigger study, and that the format and content of information provided to patients needs to be improved. The findings of the PRESTO study showed that a large trial is unlikely to be successful at this time; however, we have provided important information for future research into the treatment of these fractures.

Dupuytren's interventions surgery versus collagenase (DISC) trial: study protocol for a pragmatic, two-arm parallel-group, non-inferiority randomised controlled trial.

BACKGROUND: Dupuytren's contracture is a fibro-proliferative disease of the hands affecting over 2 million UK adults, particularly the white, male population. Surgery is the traditional treatment; however, recent studies have indicated that an alternative to surgery-collagenase clostridium histolyticum (collagenase)-is better than a placebo in the treatment of Dupuytren's contracture. There is however no robust randomised controlled trial that provides a definitive answer on the clinical effectiveness of collagenase compared with limited fasciectomy surgery. Dupuytren's intervention surgery vs collagenase trial (DISC) trial was therefore designed to fill this evidence gap. METHODS/DESIGN: The DISC trial is a multi-centre pragmatic two-arm parallel-group, randomised controlled trial. Participants will be assigned 1:1 to receive either collagenase injection or surgery (limited fasciectomy). We aim to recruit 710 adult participants with Dupuytren's contracture. Potential participants will be identified in primary and secondary care, screened by a delegated clinician and if eligible and consenting, baseline data will be collected and randomisation completed. The primary outcome will be the self-reported patient evaluation measure assessed 1 year after treatment. Secondary outcome measures include the Unité Rhumatologique des Affections de la Main Scale, the Michigan Hand Questionnaire, EQ-5D-5L, resource use, further procedures, complications, recurrence, total active movement and extension deficit, and time to return to function. Given the limited evidence comparing recurrence rates following collagenase injection and limited fasciectomy, and the importance of a return to function as soon as possible for patients, the associated measures for each will be prioritised to allow treatment effectiveness in the context of these key elements to be assessed. An economic evaluation will assess the cost-effectiveness of treatments, and a qualitative sub-study will assess participants' experiences and preferences of the treatments. DISCUSSION: The DISC trial is the first randomised controlled trial, to our knowledge, to investigate the clinical and cost-effectiveness of collagenase compared to limited fasciectomy surgery for patients with Dupuytren's contracture. TRIAL REGISTRATION: Clinical.Trials.gov ISRCTN18254597 . Registered on April 11, 2017.

Can we achieve better recruitment by providing better information? Meta-analysis of 'studies within a trial' (SWATs) of optimised participant information sheets.

BACKGROUND: The information given to people considering taking part in a trial needs to be easy to understand if those people are to become, and then remain, trial participants. However, there is a tension between providing comprehensive information and providing information that is comprehensible. User-testing is one method of developing better participant information, and there is evidence that user-tested information is better at informing participants about key issues relating to trials. However, it is not clear if user-testing also leads to changes in the rates of recruitment in trials, compared to standard trial information. As part of a programme of research, we embedded 'studies within a trial' (SWATs) across multiple ongoing trials to see if user-tested materials led to better rates of recruitment. METHODS: Seven 'host' trials included a SWAT evaluation and randomised their participants to receive routine information sheets generated by the research teams, or information sheets optimised through user-testing. We collected data on trial recruitment and analysed the results across these trials using random effects meta-analysis, with the primary outcome defined as the proportion of participants randomised in a host trial following an invitation to take part. RESULTS: Six SWATs (n=27,805) provided data on recruitment. Optimised participant information sheets likely result in little or no difference in recruitment rates (7.2% versus 6.8%, pooled odds ratio = 1.03, 95% CI 0.90 to 1.19, p-value = 0.63, I2 = 0%). CONCLUSIONS: Participant information sheets developed through user testing did not improve recruitment rates. The programme of work showed that co-ordinated testing of recruitment strategies using SWATs is feasible and can provide both definitive and timely evidence on the effectiveness of recruitment strategies. TRIAL REGISTRATION: Healthlines Depression (ISRCTN14172341) Healthlines CVD (ISRCTN27508731) CASPER (ISRCTN02202951) ISDR (ISRCTN87561257) ECLS (NCT01925625) REFORM (ISRCTN68240461) HeLP Diabetes (ISRCTN02123133).