Search

Abstract 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 β-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.

Abstract 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.

Background Young adults represent a third of the United Kingdom prison population and are at risk of poor health outcomes, including drug and alcohol misuse, self-harm and suicide. Court diversion interventions aim to reduce the negative consequences of criminal sanctions and address the root causes of offending. However, evidence of their effectiveness has not yet been established. The Gateway programme, issued as a conditional caution, aimed to improve the life chances of young adults committing low-level offences. Participants agreed not to reoffend during the 16-week caution and, following a needs assessment, received individual support from a Gateway navigator and attended two workshops encouraging analysis of own behaviour and its consequences. Objective To evaluate the effectiveness and cost-effectiveness of Gateway in relation to health and well-being of participants compared to usual process (court summons or a different conditional caution). Design, setting and participants Pragmatic, multisite, parallel-group, superiority randomised controlled trial with two 6-month internal pilots and a target sample size of 334. Randomisation between Gateway and usual process was on a 1 : 1 basis. Four Hampshire Constabulary sites recruited 18- to 24-year-old residents of Hampshire and Isle of Wight who were questioned for an eligible low-level offence. Semistructured interviews were also held with a sample of Gateway programme participants, staff and police study recruiters. Main outcome measures Primary outcome was the Warwick-Edinburgh Mental Wellbeing Scale score at 12 months. Secondary outcomes included health status, alcohol and drug use, recidivism and resource use. Results Recruitment commenced in October 2019 and the trial stopped in April 2021. A total of 191 participants were recruited, with 109 randomised to Gateway and 82 to usual process. Due to an initial overestimation of potentially eligible young people and low retention rates, recruitment targets were adjusted, and a range of mitigating measures introduced. Although recruitment broadly met study progression criteria [35/50 (70%) Pilot 1: 64/74 (86%) Pilot 2], retention was low throughout (overall: data collected at week 4 was 50%: at week 16 it was 50%: 1-year 37%). Low retention was multifactorial, with one of the main barriers being difficulties contacting participants. It was therefore not possible to complete the randomised controlled trial or the health economics analyses. Qualitative interviews held with 58 individuals yielded rare insights into the benefits and limitations of this type of intervention, as well as barriers and facilitators in relation to recruitment in this setting. Limitations Despite close collaboration with the police to address recruitment and consent issues, expansion of the inclusion criteria and recruitment area and introducing other measures, the researchers were unable to collect sufficient data within an acceptable timeframe. Conclusions The Gateway study was a unique endeavour to gather evidence for a potentially life-changing intervention for an underserved population. The experience gained indicates that randomised controlled trials of interventions, with a health-related outcome, are possible in this setting but point towards the need for conservative recruitment and retention estimates in this target population. Other study designs should be considered. The qualitative evaluation provided a range of valuable lessons for those seeking to design similar interventions or conduct research in similar settings. Study registration This study is registered as ISRCTN11888938. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR award ref: 16/122/20) and is published in full in Public Health Research; Vol. 12, No. 7. See the NIHR Funding and Awards website for further award information. Plain language summary Young adults who commit low-level offences often have many health and social needs, making them vulnerable to physical and mental health problems. The Gateway programme was a conditional caution developed to address the underlying causes of low-level offending in young people aged 18–24 years and hence improve their life chances. In Gateway, a mentor assessed the young person’s needs and supported them, signposting to healthcare, housing or other services as required. The young people also participated in two workshops, analysing the causes and consequences of their behaviour. To find out if Gateway improved health and reoffending rates, a group of those who received a Gateway conditional caution were compared with a group of those receiving a court summons or a different conditional caution. Of the 191 participants recruited to the study, 109 were randomised to Gateway and 82 to the usual process. However, the researchers had significant difficulties getting hold of the study participants on the phone and they were unable to collect enough information from them to be able to say whether Gateway worked. The researchers introduced various changes to overcome this, but in the end had to stop the study early. As part of the study, the researchers interviewed 28 Gateway programme participants, 17 Gateway project staff and 13 police officers and staff who had been recruiting into the study. From the interviews the study discovered the perceived benefits of Gateway, how programmes like this could be improved and which factors helped or got in the way of doing research in the police setting. The Gateway study aimed to provide evidence for a potentially life-changing intervention for vulnerable young adults. Although it proved impossible to complete the study, the lessons learnt from running it should help colleagues design similar programmes or plan research studies with similar populations or in similar settings. Scientific summary Background Young adults represent a third of the United Kingdom (UK) prison population and are at risk of poor health outcomes including drug and alcohol misuse, self-harm and suicide. Those aged between 18 and 24, who have been questioned as suspects in relation to a low-level offence, may need to attend court and, if convicted, face penalties such as imprisonment. However, other means aimed at preventing young adults from reoffending exist. Court diversion interventions aim to reduce the negative consequences of some types of criminal sanctions and focus resources on addressing the root causes of offending. Although diversions are widely used in the UK, evidence of their effectiveness in terms of health outcomes has not yet been established using robust research methods. Hampshire Constabulary (HC), working with local charities, developed the Gateway programme, an out-of-court disposal aimed at improving the life chances of young adults. Objectives The aim of this study was to evaluate the effectiveness and cost-effectiveness of the Gateway programme issued as a conditional caution (intervention) compared to usual process (court appearance or a different conditional caution). The study objectives were to: Examine the effectiveness of the Gateway intervention on: (1) health and well-being including alcohol and substance use, (2) access to and use of health and social services and (3) quality of life, among young adult offenders. Explore the views and experiences of victims. Assess the quantity and quality of the Gateway intervention as delivered in the study and the generalisability of the findings. Identify and measure relevant consequences, both cost and benefits, of the Gateway intervention compared with usual process. Examine the effectiveness of the Gateway intervention on recidivism. Methods Design The study undertook a pragmatic, superiority RCT with two 6-month internal pilot phases and qualitative evaluation: an economic evaluation was planned. Participants were randomised using a 1 : 1 allocation ratio to either the Gateway conditional caution (intervention) or disposal as usual to a court summons or a different conditional caution to Gateway (usual process). The qualitative evaluation aimed to capture the experiences and perceptions of the impact of the intervention on participants, the police, victims and those delivering the intervention. Participants, setting and recruitment Eligible participants were those aged 18–24 who had committed low-level offences and resided within Hampshire and Isle of Wight (IoW) area. Participants were recruited by Police investigators during processing for an offence. Potential participants were offered a chance by the police to receive the Gateway caution, and those interested were invited to take part in the study. Police officers obtained Stage 1 consent and carried out an eligibility check, after which those eligible were automatically randomised to receive either a Gateway caution or follow the usual process, such as court appearance or a different conditional caution. Qualitative interviews were undertaken with trial participants, police officers and those delivering the intervention. Sample size There is no widely accepted and established minimal clinically significant difference for the primary outcome, Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS). A change of three or more points is likely to be important to individuals. There is also variation in the standard deviation (SD) of the WEMWBS with estimates ranging from 6 to 10.8 with the pooled estimate of 10 across all studies. Assuming 90% power, 5% 2-sided statistical significance, mean difference of 4 points on WEMWBS and a SD of 10, 266 participants were required. Conservatively, assuming a 20% attrition rate, the study aimed to recruit and randomise 334 participants. Interventions The Gateway programme, issued as a conditional caution, required participants to undertake a health and social care needs assessment, attend workshops encouraging analysis of their behaviour and its consequences, and agree not to reoffend during the 16-week caution. Usual process was disposal to a court summons or an alternative conditional caution. Outcomes The primary outcome measure was the WEMWBS. Participants self-reported WEMWBS at 4-weeks, 16-weeks and 1-year post-randomisation. Secondary outcomes were health status [Short Form 12 questionnaire (SF-12)]; alcohol [Alcohol Use Disorders Identification Test (AUDIT)] and drug [Adolescent Drug Involvement Scale (ADIS)] use; type and frequency of reoffending (police data); and health and social care resource use (self-reported). Statistical methods The original plan, pre-specified in version 1.0 of the SAP, was to carry out a repeated measures, mixed-effects linear regression model with the WEMWBS score at 4-weeks, 16-weeks and 1-year post-randomisation as the dependent variable, adjusting for treatment group, time, group by time interaction, total number of records management system incidents and police national computer convictions 1-year prerandomisation, age at randomisation, Index of Multiple Deprivation quintile at randomisation, pandemic time period and standard of usual process available as fixed effects. Recruiting site was to be adjusted for as a random effect. However, due to the study closing early because of issues with retaining participants, a descriptive analysis was undertaken with no formal hypothesis testing. All outcomes were summarised descriptively by a randomised treatment group. Qualitative evaluation A qualitative evaluation was conducted to assess the implementation of the Gateway programme, including any related issues and observed benefits to the clients. Focusing on implementation, mechanisms and context, the research questions were: How is Gateway being implemented? What are the barriers to the implementation and effects of the Gateway programme? What are the mechanisms through which the intervention brings about change? How do different delivery methods (face-to-face/virtual/telephone) influence the above questions? We conducted qualitative interviews and focus groups with a range of stakeholders across three time periods during the implementation of the Gateway programme. Economic evaluation A formal health economic analysis was not feasible. Health economic data are summarised descriptively with the trial data. Results Randomised controlled trial We recruited 191 participants; 109 were randomised to Gateway and 82 to usual process. Although recruitment rates were within acceptable limits, the number of participants providing data [94 (32%) at week 4; 95 (34%) at week 16; 43 (28%) at 1-year] was insufficient to undertake any formal hypothesis testing and the trial was closed early. The groups were generally well balanced in terms of characteristics and percentage providing data, but more of those providing valid data had a previous conviction than those who did not provide data. Similar percentages from each arm provided data with those attending interviews completing all sections. Telephone interviews were acceptable to those willing to share an active telephone number. Rates for those who were non-contactable were similar between the groups at all three time points. Eighty-one of the 101 allocated to Gateway complied with the intervention. Reasons for non-compliance were reoffending and non-attendance at the LINX workshops. Qualitative evaluation Across 3 time points, 69 in-depth interviews were conducted with: 28 young people, 25 Gateway staff, 13 police recruiters and 3 focus groups with navigators. The researchers were unable to pursue interviews with victims as there were few offences with a victim. Our findings showed that, following engagement with the Gateway programme, young people reported being better able to make decisions after engagement with the LINX workshops, while navigators played a significant role in enabling compliance and change among young people. The role of the navigator was akin to that of the mentor, providing practical support towards improved health including, for example, making and attending doctors’ appointments with clients, as well as offering a listening role. Young people felt that, for them, the wider determinants (or ‘areas’) addressed with navigators, such as access to employment or improved health, were of greater importance than a reduction in reoffending. There was a polarity of needs among young people, which meant that all stakeholders valued the ability to tailor and adapt the programme to individual client’s needs, also giving clients a sense of agency and control over their lives. The independence of the Gateway intervention team, from the police, was highly valued by young people. Factors related to communication were a concern for all, particular at the point of recruitment (by police) and between multiple delivery agencies. Discussion The problems encountered throughout this trial and the researchers’ endeavours to overcome these problems provide valuable insights for colleagues seeking to design similar interventions and/or conduct studies with vulnerable populations in the police setting. Co-production is essential for studies in the police setting. By working in close collaboration with HC, and their two project dedicated officers, the researchers were able to make pragmatic adjustments to the study design as issues arose. However, training an entire police force is fraught with difficulty even when supported by senior officers; competing interests precluded mandatory training for research purposes. The use of a two-stage consent process and a web-based eligibility and randomisation tool facilitate recruitment in the police setting, but frequent, regular need to use is required to maintain the study profile. Young people who have committed an offence are known to be a difficult group to engage with generally, let alone in research. The study identified and tested implementation of different approaches to overcome this problem. Switching to telephone interviews produced a positive response. Persistence and engagement paid off, but the study was unable to solve the problem of inactive mobile telephone numbers; an issue shared by the navigators and police. Independence of those delivering the intervention is important as perceived links with the police caused some disengagement. The collected data provide valuable information on attrition rates for health studies. Interestingly, allocation did not appear to make any difference to participation. The study’s qualitative evaluation highlighted the unmet health needs for this group of 18- to 24-year-olds, and the need to address the wider determinants of reoffending through individualised assessment. The Gateway programme was, however, developed for those with higher needs, which meant that flexibility and adaptability to suit individual needs was essential. It further highlighted the invaluable role of mentors in rehabilitative programmes such as Gateway. The study has demonstrated that it is possible to recruit and randomise to a RCT in the police setting. The data that the study presents should be used to inform the planning of future trials, including anticipated attrition rates, and setting conservative targets for retention as well as recruitment rates. Internal pilots should be long enough to confirm recruitment and data collection rates are achievable over an adequate follow-up period. Given the challenges encountered, alternative study designs should be considered for the evaluation of interventions with a health-related outcome. These include: cluster RCTs where processes at individual cluster sites could be simplified; post hoc cohort studies which may address non-response and attrition bias; and regression discontinuity design (RDD), a quasi-experimental approach at lower risk of bias which has the potential to equate to a RCT. Conclusions This ambitious RCT and qualitative study provides information about an out-of-court intervention aimed at improving life chances, health and well-being and recidivism in young adults. Challenges encountered in participation and retention in this setting and the ways in which these may be addressed are described and will be useful in planning future research. Study registration This study is registered as ISRCTN11888938. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR award ref: 16/122/20) and is published in full in Public Health Research; Vol. 12, No. 7. See the NIHR Funding and Awards website for further award information.

Background The presence of dental caries impacts on children’s daily lives, particularly among those living in deprived areas. There are successful interventions across the United Kingdom for young children based on toothbrushing with fluoride toothpaste. However, evidence is lacking for oral health improvement programmes in secondary-school pupils to reduce dental caries and its sequelae. Objectives To determine the clinical and cost effectiveness of a behaviour change intervention promoting toothbrushing for preventing dental caries in secondary-school pupils. Design A multicentre, school-based, assessor-blinded, two-arm cluster randomised controlled trial with an internal pilot and embedded health economic and process evaluations. Setting Secondary schools in Scotland, England and Wales with above-average proportion of pupils eligible for free school meals. Randomisation occurred within schools (year-group level), using block randomisation stratified by school. Participants Pupils aged 11–13 years at recruitment, who have their own mobile telephone. Interventions Two-component intervention based on behaviour change theory: (1) 50-minute lesson delivered by teachers, and (2) twice-daily text messages to pupils’ mobile phones about toothbrushing, compared with routine education. Main outcome measures Primary outcome: presence of at least one treated or untreated carious lesion using DICDAS4–6MFT (Decayed, Missing and Filled Teeth) in any permanent tooth, measured at pupil level at 2.5 years. Secondary outcomes included: number of DICDAS4–6MFT; presence and number of DICDAS1–6MFT; plaque; bleeding; twice-daily toothbrushing; health-related quality of life (Child Health Utility 9D); and oral health-related quality of life (Caries Impacts and Experiences Questionnaire for Children). Results Four thousand six hundred and eighty pupils (intervention, n = 2262; control, n = 2418) from 42 schools were randomised. The primary analysis on 2383 pupils (50.9%; intervention 1153, 51.0%; control 1230, 50.9%) with valid data at baseline and 2.5 years found 44.6% in the intervention group and 43.0% in control had obvious decay experience in at least one permanent tooth. There was no evidence of a difference (odds ratio 1.04, 95% confidence interval 0.85 to 1.26, p = 0.72) and no statistically significant differences in secondary outcomes except for twice-daily toothbrushing at 6 months (odds ratio 1.30, 95% confidence interval 1.03 to 1.63, p = 0.03) and gingival bleeding score (borderline) at 2.5 years (geometric mean difference 0.92, 95% confidence interval 0.85 to 1.00, p = 0.05). The intervention had higher incremental mean costs (£1.02, 95% confidence interval −1.29 to 3.23) and lower incremental mean quality-adjusted life-years (−0.003, 95% confidence interval −0.009 to 0.002). The probability of the intervention being cost-effective was 7% at 2.5 years. However, in two subgroups, pilot trial schools and schools with higher proportions of pupils eligible for free school meals, there was an 84% and 60% chance of cost effectiveness, respectively, although their incremental costs and quality-adjusted life-years remained small and not statistically significant. The process evaluation revealed that the intervention was generally acceptable, although the implementation of text messages proved challenging. The COVID-19 pandemic hampered data collection. High rates of missing economic data mean findings should be interpreted with caution. Conclusions Engagement with the intervention and evidence of 6-month change in toothbrushing behaviour was positive but did not translate into a reduction of caries. Future work should include work with secondary-school pupils to develop an understanding of the determinants of oral health behaviours, including toothbrushing and sugar consumption, particularly according to free school meal eligibility. Trial registration This trial is registered as ISRCTN12139369. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 15/166/08) and is published in full in Health Technology Assessment; Vol. 28, No. 52. See the NIHR Funding and Awards website for further award information. Plain language summary What was the problem? Tooth decay has an impact on children and young people’s daily lives, particularly those living in deprived areas. For young children, programmes to improve toothbrushing with fluoride toothpaste help prevent tooth decay. The Brushing RemInder 4 Good oral HealTh trial (BRIGHT) investigated whether a secondary-school-based toothbrushing programme would work. What did we do? We developed a new programme which included a lesson and twice-daily text messages sent to pupils’ phones. In total, 4680 pupils, aged 11–13 years, from 42 secondary schools in the United Kingdom took part in the trial. At each school, one year group was randomly selected to receive the programme, while the other year group did not receive it. All pupils were followed up for 2.5 years to see whether there were any differences in levels of tooth decay, frequency of toothbrushing, plaque or quality of life. We also considered the programme’s value for money and the views of pupils and school staff. What did we find? We followed up 2383 pupils and found no difference in tooth decay, plaque or quality of life. We found those who had the programme were more likely to brush their teeth twice daily after 6 months than those who did not. The programme was not good value for money overall. However, the programme appeared to be of more benefit at preventing tooth decay in pupils eligible for free school meals compared to those not eligible. In the schools with more pupils eligible for free school meals, the chance of the programme representing good value for money increased. The programme was generally liked by the pupils and school staff. Some pupils found the text messages useful, although others said they were annoying. What does this mean? The programme helped pupils brush their teeth more frequently in the short term, but this did not lead to less tooth decay. Further research is needed to understand how to prevent tooth decay in secondary-school pupils. Scientific summary Background Reducing the high prevalence and severity of dental caries in the UK is a public health priority. Dental caries is largely preventable with several evidence-based child oral health promotion interventions including toothbrushing with fluoride toothpaste. However, evidence is lacking for interventions targeting toothbrushing practices to reduce dental caries and its sequelae (pain, infection and tooth loss) in secondary-school pupils. The Brushing RemInder 4 Good oral HealTh (BRIGHT) trial investigated a two-component behaviour change intervention (lesson and text messages) to prevent dental caries in secondary-school pupils. Objectives Conduct an internal pilot phase with feasibility components to: Tailor the intervention to young people. Test trial processes. Assess feasibility of within-school cluster randomisation (by year group). Investigate the intervention’s effect on caries prevalence, twice-daily toothbrushing, oral health-related quality of life and oral health behaviours. Investigate the intervention’s cost effectiveness. Explore implementation, mechanisms of impact and context through process evaluation. Methods Design A multicentre, school-based, assessor-blinded, two-arm cluster randomised controlled trial with an internal pilot phase, and embedded health economic and process evaluations. Criteria determining progression to the main phase were pre-specified and reviewed within the internal pilot phase. Setting Secondary schools in Scotland, England and Wales with above national average percentage of pupils eligible for free school meals (FSM) were recruited. Schools had to have pupils aged 11–16 years and at least 60 pupils per year group. Participant recruitment Pupils aged 11–13 years (Years 7 and 8 in England and Wales; S1 and S2 in Scotland) in participating schools were eligible to take part and received an information session about BRIGHT. Parents/carers had 2 weeks to decline their child’s participation. Pupils who had not been opted out were invited to participate by completing a consent form and providing their mobile telephone number. If they did not own a mobile telephone or could not provide their number, they were ineligible. Sample size We proposed to recruit 5040 pupils from 42 schools (84 year groups) to give 90% power to detect a reduction in the proportion of pupils with obvious decay experience from 34% to 26%, assuming: within-school (year-group level) randomisation, partial contamination effects (i.e. those contaminated gain half the treatment benefits) for 27% of the control group, recruiting an average of 60 pupils per year group, an intracluster correlation coefficient of 0.02% and 20% attrition at follow-up. A sample size of 10 schools was considered sufficient to test internal pilot objectives. Randomisation Year groups within schools were randomised 1 : 1 to the intervention or control arm. An allocation sequence, stratified by school using blocks of size two, was generated by an independent statistician. Once each school’s baseline assessments were completed, the year groups were randomised by allocation to the next available block. Trial interventions The intervention consisted of two components: (1) a 50-minute classroom-based session (CBS) about dental health delivered by teachers using a lesson plan and pupil-facing materials followed by (2) a series of twice-daily text messages to participants’ mobile phones about toothbrushing. Year groups allocated to the control arm received routine education only. Follow-up Assessment time points were baseline, after the lesson (internal pilot only), 12 weeks (internal pilot only), 6 months, 1, 2 (internal pilot only) and 2.5 years following lesson delivery. Pupils completed self-report questionnaires at all these time points. Dental examinations at baseline, 2 and 2.5 years included assessment of caries, plaque and gingival bleeding. Parents/carers were sent a resource use questionnaire at baseline, and 1, 2 and 2.5 years. Note, the descriptors of the time points for the assessments (e.g. 2.5 years) reflect the planned follow-up schedule and are used throughout the report; however, some of the actual average time intervals of follow-up varied from that planned (e.g. the actual average length of follow-up at the 2.5-year assessment was closer to 3 years as this was delayed due to disruptions caused by the COVID-19 pandemic). Primary outcome The primary outcome was the presence of at least one treated or untreated carious lesion in any permanent tooth, measured at the pupil level during the 2.5-year dental assessment using DICDAS4–6MFT (Decayed, Missing and Filled Teeth). Secondary outcomes Secondary outcomes assessed during the dental assessments were DICDAS4–6MFT at 2 years, and the following at 2 and 2.5 years: the presence of at least one treated or untreated carious lesion in any permanent tooth measured using DICDAS1–6MFT, the number of permanent DICDAS4–6MFT and DICDAS1–6MFT, plaque score (modified gingival index of Löe), bleeding score (gingival index) and number of teeth with bleeding gingivae. Participant-reported secondary outcome measures were: twice-daily toothbrushing, health-related quality of life measured by the Child Health Utility 9D (CHU9D) and oral health-related quality of life assessed using Caries Impacts and Experiences Questionnaire for Children (CARIES-QC). Statistical methods Both the clinical effectiveness and economic analyses were conducted to pre-specified and externally endorsed analysis plans. Analyses were conducted in STATA v17 (StataCorp LP, College Station, TX, USA) following the principles of intention to treat using two-sided statistical tests assessed at the 5% significance level. Baseline data were summarised descriptively overall and by randomised arm. The primary outcome was analysed using mixed-effect logistic regression, adjusting for the number of DICDAS4–6MFT and school year at baseline as fixed effects, and school as a random effect. Sensitivity analyses were conducted in which year group, nested within school, was additionally included as a random effect, and including additional covariates that were significantly associated with missing primary outcome data. A further sensitivity analysis excluded pupils whose dental assessments were completed outside of 3 months either side of the average length of follow-up for the 2.5-year time point. A complier-average causal effect (CACE) analysis, using a two-stage instrumental variable regression approach with the randomised group as the instrumental variable, was implemented to assess the impact of: attending the lesson; attending the lesson and receiving at least seven text messages a week for the first 12 weeks; and number of text messages sent. Subgroup analyses considered whether or not the intervention effect differed by FSM status, number of carious teeth at baseline and whether the school was recruited during the pilot or main trial phase. The secondary outcome of presence of at least one DICDAS1–6MFT was analysed as described for the primary outcome. The number of permanent DICDAS4–6MFT and DICDAS1–6MFT and number of teeth with bleeding gingivae were analysed using mixed-effect negative binomial regression, self-reported twice-daily toothbrushing via mixed-effect logistic regression and plaque, bleeding and CARIES-QC scores via mixed-effect linear regression. Models were adjusted for school year and associated baseline value of the outcome as fixed effects and school as a random effect. Attendance data, adverse events and safeguarding issues are summarised descriptively. Economic analysis The economic evaluation was undertaken using individual-level trial data, took the NHS perspective and generated quality-adjusted life-years (QALYs) using the CHU9D. The time horizon of the analysis was set to cover all relevant costs and outcomes. Parental questionnaires were used to collect data on dental treatments and child health-related quality of life. Other sources of cost data were used in relation to the text messages and the lesson. Results Clinical effectiveness results Of the 14,083 pupils approached in the 42 recruited schools, 4699 (33.4%) were eligible and consented and were asked to complete baseline data collection; however, 19 withdrew pre randomisation leaving 4680 pupils (92.9% of our target of 5040) included in the randomised sample (intervention, n = 2262; control, n = 2418). The average number of pupils recruited per school was 111.4 [standard deviation (SD) 35.9, median 107, range 46–189] and per year group was 55.7 (SD 21.6, median 53, range 13–119). The average age of pupils at recruitment was 12.7 years (SD 0.6), 54.2% were female and 21.9% were eligible for FSM. Over three-quarters (77.6%) reported brushing their teeth at least twice a day. There was a valid baseline dental assessment for 4625 pupils; 1603 (34.7%) had evidence of obvious decay experience (presence of DICDAS4–6MFT in at least one permanent tooth) and 2929 (63.3%) had at least one treated or untreated carious lesion in any permanent tooth (DICDAS1–6MFT). Baseline data were similar between the intervention and control groups. Confirmation of lesson delivery was received from 39 of the 42 schools, with an estimated 2016 (89.1%) of 2262 pupils randomised to the intervention group attending. Text messages were sent to 2258 (99.8%) intervention pupils. The other four withdrew shortly after receiving the lesson and so their messages were not commenced. Participants were sent text messages until they requested them to stop or until 12 July 2020 (when a technical error occurred with the text provider that meant texts stopped being sent). A total of 962 intervention participants (42.5%) withdrew from receiving the text messages, a median of 2.8 months after they commenced (range 1 day to 30 months). Participants were sent messages for between 0 and 127 weeks (approximately 30 months, mean 53.4 weeks, SD 35.4, median 62). This equated to between 1 and 1708 text messages (mean 694.5, SD 468.9, median 789). On average, 71.4% of the text messages sent to a participant were successfully delivered. At 2.5 years, 1043 out of 2383 pupils (43.8%; intervention 514, 44.6%; control 529, 43.0%) had obvious decay experience in at least one permanent tooth. There was no evidence of a difference between the intervention and control groups [odds ratio (OR) 1.04, 95% confidence interval (CI) 0.85 to 1.26, p = 0.72]. The sensitivity analyses produced similar results to the primary analysis. The CACE estimates of the treatment effect based on attending the CBS session and on attending the CBS session and receiving at least 50% of their messages per week for the first 12 weeks were similar to the intention to treat estimate (OR 1.05, 95% CI 0.85 to 1.31, p = 0.64, and 1.07, 95% CI 0.72 to 1.59, p = 0.74, respectively). The CACE estimate associated with the number of texts sent was OR 1.00 (95% CI 0.999 to 1.001, p = 0.93), which indicates that for every additional text message sent, there was no evidence of a decrease in likelihood of having a carious lesion. There was no significant interaction between treatment allocation and either number of carious teeth at baseline or pilot/main trial schools, but there was evidence of a qualitative interaction for FSM status, with a benefit of the intervention seen among FSM pupils (OR 0.69, 95% CI 0.44 to 1.08, p = 0.10) but not among non-FSM pupils (OR 1.17, 95% CI 0.93 to 1.46, p = 0.18). There was evidence of a statistically significant difference for twice-daily toothbrushing at 6 months (OR 1.30, 95% CI 1.03 to 1.63, p = 0.03) and borderline evidence of a difference in gingival index score between the two groups (geometric mean difference 0.92, 95% CI 0.85 to 1.00, p = 0.05) at 2.5 years. One non-serious adverse event was recorded during the trial, which was deemed possibly related and unexpected, for a pupil in the control group. No suspected serious pathologies were identified during dental assessments. Fifteen safeguarding issues arose during the course of the trial. All were dealt with according to the trial safeguarding procedure. Cost-effectiveness results Clinical results suggested that there was unlikely to be effects beyond 2.5 years, which was therefore set as the time horizon. Due to high rates of missing data, treatment costs were estimated from dental assessment data using multiple imputation. Text messages cost £32.53 per pupil on average, while mean dental costs over the 2.5-year follow-up were £20.73 and £21.02 for control and intervention groups, respectively. QALYs were similar in the control and intervention groups (2.196 and 2.193, respectively). Regression analysis estimated incremental costs and QALYs of the intervention, relative to the control group, to be £1.02 (95% CI −1.29 to 3.23) and −0.003 (95% CI −0.009 to 0.002), respectively, with a 7% chance that the intervention is cost-effective using a £20,000 per QALY gained threshold. The results were robust to the changes explored in the sensitivity analyses, except for an alternative approach to estimating QALYs using the CARIES-QC. While this only had a very small impact on incremental costs and QALYs, it was enough to generate an incremental QALY gain, which, in combination with a very small incremental cost, generates an incremental cost-effectiveness ratio (ICER) of £79 per QALY gained and an associated probability of the intervention being cost-effective of 96%. The subgroup analyses suggest that there is no evidence of a difference in the probability of the intervention being cost-effective within schools in Scotland versus England/Wales (6% in both cases). A positive QALY gain is observed in those schools with higher levels of pupils eligible for FSM than schools with lower levels of FSM eligibility. This produces an ICER of £2254 per QALY gained and a probability of the intervention being cost-effective of 60%. We also observed a QALY gain for pilot schools which leads to the intervention having an ICER of £3049 per QALY gained (and an 84% chance of it being cost-effective). Process evaluation The process evaluation showed that the BRIGHT intervention was generally implemented as intended, although there were challenges establishing the dose delivered and received for both components and technical difficulties delivering the text messages. Overall, pupils, staff members and stakeholders felt the intervention was acceptable. Conclusions At the 2.5-year follow-up, there was no evidence of a difference between the control and intervention groups in the prevalence of caries extending to dentine (primary outcome) or including enamel and dentine lesions. The proportion of participants with caries into dentine was high (intervention group 34.4% at baseline and 44.7% at the 2.5-year follow-up, and control group 34.9% at baseline and 43.1% at follow-up). There was an indication of a positive effect on short-term toothbrushing behaviour at 6 months. The subgroup analysis of participants eligible for FSM suggests a significant, qualitative interaction effect whereby the intervention appeared to be beneficial in terms of caries prevalence within pupils eligible for FSM but not for those not eligible for FSM. The process evaluation found the intervention to be broadly acceptable with some technical issues of text message delivery. The primary economic analysis shows that the intervention is not likely to be cost-effective. Further research is needed to understand how to prevent dental caries in secondary-school pupils. Trial registration This trial is registered as ISRCTN12139369. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 15/166/08) and is published in full in Health Technology Assessment; Vol. 28, No. 52. See the NIHR Funding and Awards website for further award information.

Background People with multiple long-term conditions are more likely to have poorer health-related quality of life (HRQOL). Yoga has the potential to improve HRQOL. Gentle Years Yoga© (GYY) is a chair-based yoga programme for older adults. We investigated the effectiveness and cost-effectiveness of the GYY programme in older adults with multiple long-term conditions. Methods In this pragmatic, multi-site, open, randomised controlled trial, we recruited adults aged ≥65 years with ≥2 long-term conditions from 15 primary care practices in England and Wales. Participants were randomly assigned to usual care control or a 12-week, group-based, GYY programme delivered face-to-face or online by qualified yoga teachers. The primary outcome was HRQOL (EQ-5D-5L) over 12 months. Secondary outcomes included anxiety, depression, falls, loneliness, healthcare resource use, and adverse events. Results Between October 2019 and October 2021, 454 participants were randomised between the intervention (n=240) and control (n=214) groups. Seven GYY courses were delivered face-to-face and 12 courses were delivered online. The mean number of classes attended among all intervention participants was nine (SD 4, median 10). In our intention-to-treat analysis (n=422), there was no statistically significant difference between trial groups in the primary outcome of HRQOL (adjusted difference in mean EQ-5D-5L = 0.020 [favouring intervention]; 95% CI -0.006 to 0.045, p=0.14). There were also no statistically significant differences in key secondary outcomes. No serious, related adverse events were reported. The incremental cost-effectiveness ratio was £4,546 per quality-adjusted life-year (QALY) and the intervention had a 79% probability of being cost-effective at a willingness-to-pay threshold of £20,000 per QALY. The intervention was acceptable to most participants and perceived as useful by some. Conclusions The offer of a 12-week chair-based yoga programme in addition to usual care did not improve HRQOL in older adults with multiple long-term conditions. However, the intervention was safe, acceptable, and probably cost-effective.

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 (

Abstract 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.

Abstract 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, I 2 = 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.

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. Plain language summary 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. Scientific summary Background The shoulder is the most frequently dislocated joint; dislocation occurs in 8.2–23.9 per 100,000 people per year, and 95% of these are anterior dislocations [Brownson P, Donaldson O, Fox M, Rees JL, Rangan A, Jaggi A, et al. BESS/BOA Patient Care Pathways: Traumatic anterior shoulder instability. Shoulder Elbow 2015;7(3):214–26]. They occur when excessive forces during a traumatic event displace the humeral head frontwards, out of the shoulder socket (glenoid fossa), resulting in the joint surfaces completely losing contact [Brownson et al. 2015; Hanchard NC, Goodchild LM, Kottam L. Conservative management following closed reduction of traumatic anterior dislocation of the shoulder. Cochrane Database Syst Rev 2014;(4):CD004962; Berendes TD, Pilot P, Nagels J, Vochteloo AJ, Nelissen RG. Survey on the management of acute first-time anterior shoulder dislocation amongst Dutch public hospitals. Arch Orthop Trauma Surg 2015;135(4):447–54]. People with a traumatic anterior shoulder dislocation (TASD) may have ongoing pain, disability and substantial morbidity linked to high recurrence rates and subsequent need for repeated episodes of management (Brownson et al. 2015; Hanchard et al. 2014; Berendes et al. 2015). Re-dislocation following a first-time traumatic event typically occurs within 12 months of the index dislocation [Zacchilli MA, Owens BD. Epidemiology of shoulder dislocations presenting to emergency departments in the United States. J Bone Joint Surg Am 2010;92(3):542–9]. Rehabilitation may reduce ongoing re-dislocations and restore a functional, painless and stable shoulder through early restoration of joint movement and promotion of exercises to retrain muscles to maintain stability (Hanchard et al. 2014). However, a 2014 Cochrane review did not find an evidence base to support this (Hanchard et al. 2014). Dutch national guidelines explicitly state no referral to physiotherapy should be made, and UK guidelines cite referral ‘may be helpful’ (Brownson et al. 2015; Berendes et al. 2015). Consequently, the nature and extent of physiotherapy required for the management of patients following TASD are unclear. A typical course of six physiotherapy sessions costs around £378; a single assessment and advice session costs £63 (NHS Reference cost). In addition to the cost of providing a physiotherapy service, there was a clear message from our patient workshop that attending a typical course of six sessions of physiotherapy is burdensome. Younger people may need to take time from work or arrange care for dependents, while older people may find travel challenging, particularly if unable to drive following the dislocation. For both groups, this can be time-consuming and costly. If a single advice session were all that is required, it would have a positive impact on patient experience after TASD, lessening the burden on patients and their friends and families. Consequently, a course of supervised, tailored physiotherapy needs to be of clear additional benefit, when compared to a single session of advice, if it is to be implemented as standard care in the NHS. There is no clinical consensus or high-quality evidence on how best to manage TASDs (Brownson et al. 2015). Objective The primary objective was to test a single session of advice and physiotherapy versus a single session of advice only, for adults with first-time TASD managed non-operatively at 6 months using the Oxford Shoulder Instability Score (OSIS). Methods Design A UK multicentre, two-arm, parallel group, superiority, randomised controlled trial (RCT) with 1 : 1 treatment allocation, across 41 NHS sites, with embedded qualitative study. A protocol paper has been previously published [Kearney RS, Dhanjal G, Parsons N, Ellard D, Parsons H, Haque A, et al. Acute Rehabilitation following Traumatic anterior shoulder dISlocAtioN (ARTISAN): protocol for a multicentre randomised controlled trial. BMJ Open 2020;10(11):e040623]. The final protocol, statistical analysis plan and health economic analysis plan are publicly available. Participants People were eligible to be included in the trial if they were adults (≥ 18 years) with a first-time TASD confirmed radiologically. People were excluded if they had neurovascular complications or bilateral dislocations, were unable to adhere to trial procedures or unable to attend physiotherapy within 6 weeks of injury, or had been previously included in the trial. After potential participants were assessed, informed written consent was obtained by a site-based researcher trained in good clinical practice. Intervention All participating centres received an initial training session from an Acute Rehabilitation following Traumatic anterior shoulder dISlocAtioN (ARTISAN) trial research physiotherapist. Following this, a lead physiotherapist at each site was identified to complete subsequent training of additional physiotherapists. This training was supported with web-based materials and a trial intervention manual. A quality control programme ensured intervention fidelity. Fidelity was monitored by: (a) direct observations by a member of the trial team; (b) audio recordings, used to assess the success or failure of the therapist to introduce the aims/rationale of each component and consolidate participant learning at the end of each component; and (c) a therapist self-report form completed for every trial participant. Points (a) and (b) were evaluated twice annually for the duration of recruitment and intervention delivery. Any issues identified were discussed on a case-by-case basis by the trial management group, who were responsible for recommending appropriate action. If issues with individual sites were not resolved following the recommendations, they were escalated to the trial steering committee. All participants had an initial period where the injured arm was supported in a sling, and then received an appointment for a physiotherapy advice session within 6 weeks of their injury. At the first appointment, all participants received the same initial shoulder examination followed by advice to aid self-management, lasting up to 1 hour and administered by an ARTISAN-trained physiotherapist. This included core components on education, progressive exercises, and exercise planning to enhance self-management behaviours. These core components were available after the advice session via a password-protected website or via paper-based alternatives at the participants’ preference. Details of the intervention development were first published in December 2021 [Liew Z, Mazuquin B, Ellard DR, Karasouli E, Drew S, Modi C, et al. Development of a single-session physiotherapy and self-management intervention for the treatment of primary traumatic anterior shoulder dislocation for the ‘Acute Rehabilitation following Traumatic anterior shoulder dISlocAtioN (ARTISAN)’ multicentre RCT. Physiotherapy 2021;113:80–7]. Following completion of the advice appointment, the participant was randomised, allocating them to this advice session alone or to this advice session plus the offer of additional physiotherapy. We defined the offer of additional physiotherapy to be the intervention. Participants randomised to advice only were provided with a contact point to self-refer back to the clinical team if recovery did not occur. Participants who self-referred back to the clinical team were considered to be per protocol. Participants randomised to receive additional physiotherapy were offered additional physiotherapy sessions. Each additional session lasted for up to 30 minutes, over a maximum duration of 4 months from the date of randomisation. The course of physiotherapy involved teaching and supervising the ‘core set’ of progressive exercises offered to the control arm in addition to being able to tailor treatment according to usual practice. Outcome measures Primary outcome measure The primary outcome measure was the OSIS. The OSIS is a self-completed outcome measure containing 12 questions (0–4 points each), with possible scores from 0 (worst function) to 48 (best function) [Dawson J, Fitzpatrick R, Carr A. The assessment of shoulder instability. The development and validation of a questionnaire. J Bone Joint Surg Br 1999;81(3):420–6; Dawson J, Rogers K, Fitzpatrick R, Carr A. The Oxford shoulder score revisited. Arch Orthop Trauma Surg 2009;129(1):119–23]. These questions relate to activities of daily living particularly relevant to patients exhibiting shoulder instability. Secondary outcome measures The secondary outcome measures were as follows. QuickDASH: The QuickDASH is a self-completed shortened version of the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire. Instead of 30 items, the QuickDASH uses 11 items to measure physical function and symptoms in people with any or multiple musculoskeletal disorders of the upper limb. The questionnaire was designed to help describe the disability experienced by people with upper-limb disorders and also to monitor changes in symptoms and function over time [Gummesson C, Ward MM, Atroshi I. The shortened Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH): validity and reliability based on responses within the full-length DASH. BMC Musculoskelet Disord 2006;7:44]. EuroQol-5 Dimensions, five-level version (EQ-5D-5L): EQ-5D-5L is a well-validated, generic health-related quality of life measure consisting of five dimensions, each with five levels of response. Each combination of answers can be converted into a health utility score. It has good test–retest reliability, is simple for participants to use, and gives a single preference-based index value for health status that can be used for broader cost-effectiveness comparative purposes [Herdman M, Gudex C, Lloyd A, Janssen M, Kind P, Parkin D, et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res 2011;20(10):1727–36]. Complications: Serious adverse events (SAEs) were reported through the following mechanisms: (a) participant reported during routine collection of follow-up data; (b) local research teams reported any additional investigations or treatment of participants; (c) local physiotherapists delivering the trial interventions reported any events occurring during treatment sessions; and (d) medical records of non-responding participants were retrieved by local research teams at site. Serious adverse events not related to the intervention or TASD event were recorded on the SAE form but were not formally analysed or reported. SAEs that were predefined complications directly related to the trial interventions or directly caused by the primary TASD event were recorded as complications and were formally analysed and reported. Resource use questionnaires: The primary health economic analysis concentrated on direct intervention and healthcare/personal social services costs, while wider impact (societal) costs were included within the sensitivity analyses. Participants completed resource use questionnaires at all follow-up points to collect resource use data associated with the interventions under examination. We used techniques common in long-term studies to ensure minimum loss to follow-up, such as collection of multiple contact addresses and telephone numbers, mobile telephone numbers and e-mail addresses. All outcome measures were collected at baseline, 6 weeks, and 3, 6 and 12 months following randomisation. Qualitative interviews: One of the secondary objectives for ARTISAN was to qualitatively explore the participant experiences of receiving the trial treatments and facilitators and obstacles to adhering to them. Soon after the return of the 12-month follow-up questionnaire, a purposive sample (informed by treatment allocation, gender, age and outcome) of up to 50 participants were invited for one-off face-to-face interviews [by telephone or via Microsoft Teams® (Microsoft Corporation, Redmond, WA, USA)]. The aim was to explore the participant experience of receiving the trial treatments, and facilitators and obstacles to adhering to them. Results Between 14 November 2018 and 14 March 2022 we recruited from 41 NHS Trusts, who screened 1551 adults with a traumatic shoulder dislocation, from whom 1069 were not randomised. Forty of the 41 NHS Trust teams randomised the remaining 482 to advice only (n = 240) or advice and a programme of physiotherapy (n = 242). Ten participants withdrew prior to the primary outcome point of 6 months; 354 participants completed the primary outcome OSIS (73%) and were included in the final analysis. Across the groups there were high levels of adherence. Ninety-six physiotherapists delivered the interventions across the 41 sites. Two participants in the advice-only group (n = 240) crossed over to receive a programme of physiotherapy because in the opinion of the treating clinician a programme of further physiotherapy was needed. A further 42 participants self-referred to receive a programme of physiotherapy. A total of 194 participants received advice only, and there were missing data on two participants. In the group randomised to advice and further physiotherapy, 24 participants did not attend any additional appointments, 30 participants did not attend after one appointment, 167 had a complete programme of physiotherapy and 18 were receiving ongoing management after the 4-month period. There were three participants with missing data. There was no evidence of a statistically significant difference in OSIS between advice only and advice plus a programme of physiotherapy in the 6-month primary outcome, for the primary intention-to-treat adjusted analysis [favours physiotherapy: 1.5, 95% confidence interval (CI) −0.30 to 3.5] or at earlier 3-month and 6-week time points. At each time point the direction of change favoured a programme of physiotherapy; however, the 95% CI at each time point excluded our target four-point difference on the OSIS. There were no statistically significant differences in the QuickDASH or consistent differences in the EQ-5D-5L secondary outcomes. Secondary unadjusted and per-protocol analyses, and a sensitivity analysis accounting for missingness, were not materially different. Predefined subgroup analyses were undertaken to assess whether there was evidence that the intervention effect differed between age group (≤ 39 years old and ≥ 40 years old) and arm dominance. Our predefined subgroup analyses showed no evidence of clinically relevant effects from either age or arm dominance. Predefined complications profiles were similar across the two groups. In the advice group, there were reports of 7 shoulder re-dislocations, 3 frozen shoulders, 8 compression fractures of the shoulder, 22 rotator cuff tears and 1 report of nerve damage. In the additional physiotherapy group, there were 3 shoulder re-dislocations, 7 frozen shoulders, 21 rotator cuff tears and 4 compression fractures of the shoulder. Participants randomised to a programme of physiotherapy had non-significant increase in quality of life of 0.019 quality-adjusted life-years (QALYs) (95% CI −0.0005 to 0.0375) at a small, non-significant increased cost of £64 (95% CI −61 to 191) over the follow-up period. The probability of being cost-effective at a willingness-to-pay threshold of £30,000 was 0.946. Sensitivity analyses, including complete cases only and including broader societal costs, provided similar findings. Thirty-one participants were interviewed from both arms of the trial: ARTISAN [n = 16, 8 male and 8 female, mean age 49 years (standard deviation 21 years)] and ARTISAN Plus [n = 15, 11 male and 4 female, mean age 59 years (standard deviation 17 years)]. Four interlinked themes emerged from the data: (1) feelings about their shoulder rehabilitation outcome; (2) judgement of ARTISAN rehabilitation materials; (3) assessment of shoulder rehabilitation services provision; and (4) experiences of involvement in ARTISAN. The data reveal that generally across both arms of the trial, participants’ experiences were good. There are a number of areas where there are differences related to age and participants’ requirements to return to sporting activities. In terms of recovery following their rehabilitation journey, there is a trend towards a more positive outcome reported by those in the ARTISAN Plus arm of the trial. Conclusions We found little difference in the primary outcome (OSIS) or other secondary outcomes. Advice with additional physiotherapy sessions is cost-effective at a £30,000/QALY threshold. However, the small imprecise health gains raise questions on whether it is the best use of scarce physiotherapy resources given current service demands. The ARTISAN trial is the largest RCT for the common shoulder dislocation. The study recruited 482 participants, across 41 NHS Trusts and using 96 ARTISAN-trained physiotherapists, making the sample representative of NHS patients. Adherence to trial groups was high, with 99% in the advice group being offered advice only and 100% in the additional physiotherapy group being offered additional physiotherapy. The advice-only intervention was delivered by physiotherapists and crucially did not prohibit patients from self-referring back to the service if recovery did not meet their expectations. With this mechanism in place, 18% (42/240) self-referred back to the service. Empowering people to make their own treatment decisions was acceptable to clinicians (99% adherence) and allows flexibility for patients to decide when additional supervised treatment is required. It is acknowledged that there will be circumstances where additional supervised physiotherapy is appropriate; however, as a default referral pathway, it is not clinically superior to an advice-only intervention. The ARTISAN trial found evidence that there is little difference between referring people to a programme of physiotherapy or to a single session of advice with a physiotherapist. However, people who are not experiencing recovery as expected could self-refer for a supervised programme of physiotherapy. This will provide a balance between best use of NHS resources, empowering patients, and reducing unnecessary appointments for those who can self-manage. 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.

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.

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. Plain language summary 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. Scientific summary Background Lateral compression type-1 (LC-1) pelvic fractures are a common fragility fracture in older adults. Older patients who do not get back walking following an LC-1 fracture due to ongoing pain are at greater risk of immobility-related complications. In the UK, standard treatment for LC-1 fragility fracture is to ‘mobilise as pain allows’, involving prescribing pain relief, getting patients up within a few days of injury with physiotherapy input and encouraging them to mobilise with an assistive device until the fracture heals. This is unlike fragility hip fractures (fractures involving the upper end of the femur) where there is evidence that early surgery (within 1–2 days) is associated with reduced risk of death and pressure sores and these fractures are usually treated surgically. Despite LC-1 fractures being similarly disabling for some patients in terms of pain and immobility and occurring in the same patient group as hip fractures, to date, it has not been shown whether elderly patients with LC-1 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 (INFIX) compared to non-surgical management of LC-1 fragility fractures in older adults (L1FE trial): undertake a 12-month internal pilot to obtain robust estimates of recruitment and confirm trial feasibility undertake a parallel group multicentre randomised controlled trial (RCT) to assess the effectiveness of surgical fixation with INFIX versus non-surgical management of LC-1 fragility fractures in older adults undertake an economic evaluation to compare the cost effectiveness of surgical fixation compared to non-surgical management, to determine the most efficient provision of future care and to describe the resource impact on the NHS for the two treatment options undertake a long-term review of patient well-being [EuroQol-5 Dimensions, five-level version (EQ-5D-5L) and mortality] 12 months after entering the trial. Design Pragmatic, randomised controlled superiority trial, with 12-month internal pilot to assess recruitment assumptions, and an economic evaluation. Participants were randomised between INFIX surgical fixation and non-surgical management of LC-1 pelvic fracture with a 1 : 1 allocation ratio. The target sample size was 600 participants. For the internal pilot the target was to set up a minimum of 19 recruitment sites and randomise 148 participants in order to meet the target sample size in the main trial. To progress to the main trial, an average recruitment rate of one participant per centre per month was required. Setting and participants Participants were recruited from Major Trauma Centres (MTCs) in the UK. Adults aged 60 years or older with an LC-1 pelvic fracture, arising from a low-energy fall from standing height or less, and unable to mobilise independently to a distance of around 3 m and back due to pelvic pain 72 hours after injury were eligible for inclusion. Interventions Internal fixation device surgical fixation and non-surgical management (both groups received pain relief and were seen by a physiotherapy team who worked to mobilise the patients as pain allowed). Internal fixation device surgery uses an INFIX to stabilise the pelvis. INFIX devices have screws that are secured into the pelvic bone, and these are connected by a metal bar across the front of the patient. The INFIX device sits entirely under the patient’s skin. Main outcome measures Primary outcome – average patient health-related quality of life, over 6 months, assessed by the patient-reported outcome measure, EQ-5D-5L utility score. Collected at baseline, 2 weeks, 6 weeks, 12 weeks and 6 months post-randomisation time points. Secondary outcomes – health-related quality of life using the EQ-5D-5L visual analogue scale (VAS); physical function using the eight-item Patient-Reported Outcome Measures Information System (PROMIS) lower extremity function (LEF) (mobility) – Short Form and Timed Up and Go (TUG) test; mental health using the PROMIS Scale v1.2 – Global Health Mental 2a subscale; pelvic pain using a VAS; delirium using the Abbreviated Mental Test Score (AMTS) and 4AT Rapid Assessment Test for Delirium; displacement of the pelvis based on a radiological assessment at the 12-week visit; mortality; complications and adverse events including lateral cutaneous nerve injury which was an adverse event of special interest (AESI); resource use; long-term review of patient well-being using the EQ-5D-5L and mortality at 12 months (optional follow-up for those recruited early in the trial). Information on resource use such as length of hospital stay, medication use, surgery details and details of rehabilitation therapy received was collected throughout the follow-up period to assess the impact on the NHS as part of the economic evaluation. Sample size Sample size was calculated based on the primary outcome, EQ-5D-5L. To be conservative, we took the lowest published estimate of the minimal clinically important differences (MCID) (0.074) with an estimated standard deviation (SD) of 0.25 (estimated from the 0.30 reported for the 3L version and adjusted down to account for the 5L version’s greater sensitivity). Based on these assumptions we would have needed to analyse 480 participants (240 per group) and, after accounting for loss to follow-up of 20%, we would have needed to recruit and randomise 600 participants for a study with 90% power (2p = 0.05). Randomisation Intervention allocation was assigned using an online data management system developed for the L1FE study by the software team at York Trials Unit (YTU). There was independent and concealed random allocation (1 : 1 ratio), using computer-generated random permuted blocks of random sizes (4, 6 and 8), stratified by centre, following confirmation of eligibility and written consent. Analysis The originally planned primary analysis was a mixed-effects linear regression model, with EQ-5D-5L scores at 2, 6 and 12 weeks and 6 months follow-up as the dependent variable, adjusting for baseline EQ-5D-5L, randomised group and other pertinent baseline characteristics as fixed effects. The plan was to control for potential clustering at hospital site level by including it in the model as a random effect and to account for the correlation of scores within patients over time by means of an appropriate covariance structure. Due to the small sample size and stopping at the end of the internal pilot, a descriptive analysis was undertaken with no formal hypothesis testing. All reported summary statistics are given at both a treatment group and overall level. The planned economic analysis was to examine the overall difference in EQ-5D-5L index scores between the two groups using regression methods, consistent with the model selected in the statistical analysis. The EQ-5D-5L health states were to be valued in accordance with National Institute for Health and Care Excellence (NICE) guidance. Quality-adjusted life-years (QALYs) were to be calculated by plotting the utility scores at each of the four time points and estimating the area under the curve and regression methods used to express the incremental cost per QALYs gained. Results were to be presented using incremental cost-effectiveness ratios (ICERs) and cost-effectiveness acceptability curves (CEACs). Results The trial closed early, at the end of the internal pilot due to low recruitment. The internal pilot took place in two separate phases (August 2019 to March 2020 and March 2021 to September 2021) because of a 1-year recruitment pause due to the coronavirus disease 2019 (COVID-19) pandemic. Site set-up Eleven sites in England and Wales were opened during the first phase of the internal pilot. Ten of these re-opened following the study recruitment pause. A further 10 sites, including 3 in Scotland, were interested in participating and were in various stages of set-up prior to study closure. The 11 sites were open for a combined total of 92 months. Patient screening During the internal pilot, 316 patients were assessed for eligibility, of whom 43 were eligible (13.6%). The main reasons for ineligibility were: patient able to mobilise independently 3 m and back (n = 161), concomitant injury that impedes mobilisation (n = 57), surgery contraindicated (n = 40), patient did not have a low-energy LC-1 pelvic fracture (n = 38), unable to schedule surgery within 10 days of injury (n = 34), patient was under 60 years of age (n = 23) and/or the patient was non-ambulatory or required assistance prior to injury (n = 22). Recruitment, withdrawals and follow-up Of the 43 eligible participants, 36 (83.7%) were approached for consent, of whom 11 (30.6%) provided consent. Eleven (100%) of the consenting patients were randomised into the study. 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). The average recruitment rate per site per month was 0.175, well below the target rate of one patient per site per month. Eleven patients were randomised, five to INFIX surgical fixation and six to non-surgical management. Three participants in the non-surgical management group were withdrawn from the study. One participant died, one participant lost capacity and their family member no longer wanted them to take part in the study and one participant had sight problems and considered themselves too frail to continue. Of the five participants randomised to surgical fixation, all received surgery and no one in the non-surgical management group received surgery. All participants in the surgical fixation group completed the 6-month questionnaires and the remaining participants in the non-surgical management group provided data at 6 months (3/6). The average age of participants was 83.0 years (interquartile range 76.0–89.0) and the EQ-5D-5L utility score at 6 months post randomisation (n = 8) was 0.32 (SD 0.37). Barriers to recruitment and actions taken There were multiple barriers to recruitment, which, combined with the impact of COVID-19 on the NHS, resulted in a very low recruitment rate. These included: Fewer patients than anticipated were screened and screening activity was variable across sites. Patients had multiple entry points to hospital for treatment with onward admissions to several possible departments (Geriatric ward, Orthopaedic ward, Medical ward or an Admissions unit). This made screening resource-intensive for the research teams at sites. This became particularly challenging following the recruitment pause, as recruiting staff at sites were not all back to full capacity. A substantial proportion of patients were able to mobilise by 72 hours post injury and therefore did not meet the eligibility criteria for the trial. There was also variation across sites in how the assessment of mobility was undertaken and the extent of assistance provided to patients. The COVID-19 pandemic led to a concerted focus on avoidance of hospital admissions where possible, thereby minimising hospital stays. Because the pre-trial standard care for LC-1 pelvic fragility fractures was non-surgical management, there were challenges in the delivery of the L1FE trial. Patients were increasingly being discharged before the 72-hour assessment to nursing homes, residences with care packages or rehabilitation hospitals and could not be screened for the trial. There was evidence of a lack of equipoise amongst both surgical and non-surgical healthcare professionals, with a preference for non-surgical management in some centres. For example, some surgeons felt that INFIX was not a good treatment for this patient cohort, or they felt that most patients could mobilise fairly quickly. The recruiting window was relatively small. There were 3 days before the initial approach was permitted, with the surgery required to take place before day 10 (but in reality, this was often shorter due to 1 day per week operating lists or no operating at weekends at some sites). Making a decision about participating in a trial where the interventions are very different in intensity and risks is potentially a daunting one for patients and their consultees (where patients lacked capacity). From the perspective of recruiting staff, the resulting consent process was experienced as time consuming, involving difficult conversations and a lot of back-and-forth, waiting for patients to discuss the trial with their relatives and/or surgeon, or for next of kin to do so. This was exacerbated by the COVID-19 pandemic. Where patients lacked capacity, discussions with consultees had to take place remotely and recruitment staff felt that it was more difficult to build rapport and trust. There was a perception amongst staff that patients’ next of kin were also reluctant to consent on behalf of the patient whom they were unable to see due to COVID-19 visiting restrictions, in order to have a better idea of how they were doing, or get a better sense of the study. We used multiple strategies to mitigate against the barriers identified. We used cross-site meetings with the aim of bringing together research staff at recruiting sites to discuss the challenges with recruitment experienced at each site, share knowledge and provide support from the central trial team. We obtained approval for changes to the protocol clarifying how the 72-hour mobility inclusion criterion was implemented. During the recruitment pause we developed new resources to support recruitment staff: a short video introduction to the trial that sites could share across departments; a narrated animation on identifying patients across departments; a video resource on how to undertake the 72-hour mobility assessment for the trial; a patient-facing consent video; and updated consent guidance. We obtained approval for the associate principal investigator (API) scheme to be extended to orthogeriatricians to increase their engagement with the study. The trial team including the chief investigator (CI), physiotherapist, orthogeriatrician and trial co-ordinators provided support to address issues at individual sites. With the input of our patient and public involvement (PPI) group, the patient information sheet (PIS) was also revised. Despite the efforts of the central trial team and recruiting teams at sites, the strategies did not sufficiently mitigate against the barriers. Conclusions It is 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. 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.

Introduction Randomised controlled trials (RCTs) inform healthcare decisions. It is now apparent that some published RCTs contain false data and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs that have been conducted on a given topic. While it is usual to assess methodological features of the RCTs in the process of undertaking a systematic review, it is not usual to consider whether the RCTs contain false data. Studies containing false data therefore go unnoticed and contribute to systematic review conclusions. The INveStigating ProblEmatic Clinical Trials in Systematic Reviews (INSPECT-SR) project will develop a tool to assess the trustworthiness of RCTs in systematic reviews of healthcare-related interventions.Methods and analysis The INSPECT-SR tool will be developed using expert consensus in combination with empirical evidence, over five stages: (1) a survey of experts to assemble a comprehensive list of checks for detecting problematic RCTs, (2) an evaluation of the feasibility and impact of applying the checks to systematic reviews, (3) a Delphi survey to determine which of the checks are supported by expert consensus, culminating in, (4) a consensus meeting to select checks to be included in a draft tool and to determine its format and (5) prospective testing of the draft tool in the production of new health systematic reviews, to allow refinement based on user feedback. We anticipate that the INSPECT-SR tool will help researchers to identify problematic studies and will help patients by protecting them from the influence of false data on their healthcare.Ethics and dissemination The University of Manchester ethics decision tool was used, and this returned the result that ethical approval was not required for this project (30 September 2022), which incorporates secondary research and surveys of professionals about subjects relating to their expertise. Informed consent will be obtained from all survey participants. All results will be published as open-access articles. The final tool will be made freely available.

Abstract Background Proximal humerus fractures (PHF) are common and painful injuries, with the majority resulting from falls from a standing height. As with other fragility fractures, its age-specific incidence is increasing. Surgical treatment with hemiarthroplasty (HA) and reverse shoulder arthroplasty (RSA) have been increasingly used for displaced 3- and 4-part fractures despite a lack of good quality evidence as to whether one type of arthroplasty is superior to the other, and whether surgery is better than non-surgical management. The PROFHER-2 trial has been designed as a pragmatic, multicentre randomised trial to compare the clinical and cost-effectiveness of RSA vs HA vs Non-Surgical (NS) treatment in patients with 3- and 4-part PHF. Methods Adults over 65 years of age presenting with acute radiographically confirmed 3- or 4-part fractures, with or without associated glenohumeral joint dislocation, who consent for trial participation will be recruited from around 40 National Health Service (NHS) Hospitals in the UK. Patients with polytrauma, open fractures, presence of axillary nerve palsy, pathological (other than osteoporotic) fractures, and those who are unable to adhere to trial procedures will be excluded. We will aim to recruit 380 participants (152 RSA, 152 HA, 76 NS) using 2:2:1 (HA:RSA:NS) randomisation for 3- or 4-part fractures without joint dislocation, and 1:1 (HA:RSA) randomisation for 3- or 4-part fracture dislocations. The primary outcome is the Oxford Shoulder Score at 24 months. Secondary outcomes include quality of life (EQ-5D-5L), pain, range of shoulder motion, fracture healing and implant position on X-rays, further procedures, and complications. Independent Trial Steering Committee and Data Monitoring Committee will oversee the trial conduct, including the reporting of adverse events and harms. Discussion The PROFHER-2 trial is designed to provide a robust answer to guide the treatment of patients aged 65 years or over who sustain 3- and 4-part proximal humeral fractures. The pragmatic design and recruitment from around 40 UK NHS hospitals will ensure immediate applicability and generalisability of the trial findings. The full trial results will be made available in a relevant open-access peer-reviewed journal. Trial registration ISRCTN76296703. Prospectively registered on 5th April 2018

Aims: Early large treatment effects can arise in small studies, which lessen as more data accumulate. This study aimed to retrospectively examine whether early treatment effects occurred for two multicentre orthopaedic randomized controlled trials (RCTs) and explore biases related to this. Methods: Included RCTs were ProFHER (PROximal Fracture of the Humerus: Evaluation by Randomisation), a two-arm study of surgery versus non-surgical treatment for proximal humerus fractures, and UK FROST (United Kingdom Frozen Shoulder Trial), a three-arm study of two surgical and one non-surgical treatment for frozen shoulder. To determine whether early treatment effects were present, the primary outcome of Oxford Shoulder Score (OSS) was compared on forest plots for: the chief investigator’s (CI) site to the remaining sites, the first five sites opened to the other sites, and patients grouped in quintiles by randomization date. Potential for bias was assessed by comparing mean age and proportion of patients with indicators of poor outcome between included and excluded/non-consenting participants. Results: No bias in treatment effect was observed overall for the CI site, or the first five sites, compared with the remaining sites in either trial. An early treatment effect on the OSS was observed for the first quintile of participants recruited to ProFHER only (clinically relevant difference of seven points). Selection bias for age was observed in the ProFHER trial only, with slightly younger patients being recruited into the study. Both trials showed some selection bias for markers of poor prognosis, although these did not appear to change over time. Conclusion: No bias in treatment effects overall were found at the CI or early sites set-up. An early treatment effect was found in one of the two trials, which was likely a chance effect as this did not continue during the study. Selection bias was observed in both RCTs, however this was minimal and did not impact on outcome. Cite this article: Bone Jt Open 2023;4(2):96–103.

Abstract Background Lateral compression type1 (LC-1) fragility fractures are a common, painful injury in older adults resulting in reduced mobility. The incidence of these fractures is increasing with the growing older adult population. The current standard of care is non-surgical management; however, patients with this injury are at risk of long-term immobility and related complications. INFIX is a pelvic fixation device used in younger patients with high-energy fractures. The device is fitted via a percutaneous technique with no external pin sites and has good purchase even in osteoporotic bone. It therefore has the potential to be well tolerated in patients with LC-1 fragility fractures. INFIX could improve patients’ ability to mobilise and reduce the risk of immobility-related complications. However, there is a risk of complications related to surgery, and robust evidence is required on patient outcomes. This study will investigate the clinical and cost-effectiveness of surgical fixation with INFIX compared to non-surgical management of LC-1 fragility fractures in older adults. Methods A multi-centre randomised controlled trial of 600 patients allocated 1:1 to non-surgical management or INFIX surgery. The study will have a 12-month internal pilot to assess recruitment and trial feasibility. The primary outcome will be the patient quality of life over 6 months, measured by the patient-reported EQ-5D-5L. The secondary outcomes will include physical function, mental health, pain, delirium, imaging assessment, resource use, and complications. Discussion The L1FE study aims to compare the clinical and cost-effectiveness of surgical and non-surgical management of people aged 60 years and older with LC-1 fragility fractures. The trial is sufficiently powered and rigorously designed to inform future clinical and patient decision-making and allocation of NHS resources. Trial registration International Standard Randomised Controlled Trial Number Registry ISRCTN16478561. Registered on 8 April 2019

Abstract 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

Abstract 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).

Background: Poor response rates to follow-up questionnaires can adversely affect the progress of a randomised controlled trial and the validity of its results. This embedded ‘study within a trial’ aimed to investigate the impact of including a pen with the postal 3-month questionnaire completed by the trial participants on the response rates to this questionnaire. Methods: This study was a two-armed randomised controlled trial nested in the Gentle Years Yoga (GYY) trial. Participants in the intervention group of the GYY trial were allocated 1:1 using simple randomisation to either receive a pen (intervention) or no pen with their 3-month questionnaire (control). The primary outcome was the proportion of participants sent a 3-month questionnaire who returned it. Secondary outcomes were time taken to return the questionnaire, proportion of participants sent a reminder to return the questionnaire, and completeness of the questionnaire. Binary outcomes were analysed using logistic regression, time to return by Cox Proportional hazards regression and number of items completed by linear regression. Results: There were 111 participants randomised to the pen group and 118 to the no pen group who were sent a 3-month questionnaire. There was no evidence of a difference in return rates between the two groups (pen 107 (96.4%), no pen 117 (99.2%); OR 0.23, 95% CI 0.02 to 2.19, p=0.20). Furthermore, there was no evidence of a difference between the two groups in terms of time to return the questionnaire (HR 0.90, 95% CI 0.69 to 1.18, p=0.47), the proportion of participants sent a reminder (OR 0.85, 95% CI 0.48 to 1.53, p=0.60) nor the number of items completed (mean difference 0.51, 95% CI -0.04 to 1.06, p=0.07). Conclusion: The inclusion of a pen with the postal 3-month follow-up questionnaire did not have a statistically significant effect on response rate.

Abstract Background and Aims During the COVID‐19 pandemic, US Food and Drug Administration (FDA) permitted emergency use authorizations (EUAs) for vaccines/treatments with promising data. Eight treatments were issued EUAs by May 31, 2021; one of these was approved (Remdesivir for certain populations) and two were revoked (chloroquine phosphate/hydroxychloroquine and bamlanivimab) by September 30, 2021. The aim of this study is to find out what evidence the EUAs were based on and how many studies were published while they remained active (up to September 30, 2021). Methods A review of published clinical studies for the 6 months before each EUA was issued, and the time after (until September 30, 2021, or until revoked). PubMed and the identified systematic reviews were the sources for identifying published literature. Results The number of clinical studies published pre‐EUA varied from a single case study (for chloroquine phosphate/hydroxychloroquine) to numerous studies of multiple types (for convalescent plasma). Four treatments had a single randomized controlled trial (RCT) as evidence (bamlanivimab monotherapy, REGN‐COV, bamlanivimab + etesevimab, sotrovimab) and two also had other study types (remdesivir and baricitinib). The number of clinical studies published post‐EUA (for those active on September 30, 2021) was widely varied. Eighteen RCTs were published for Convalescent plasma, while Remdesivir had eight. Baricitinib, REGN‐COV, and bamlanivimab + etesevimab all had one, but none were published for sotrovimab. Conclusion The number of trials for treatments with EUAs was limited in all cases before the EUA was issued, and in most cases for those with EUAs ongoing at the end of September 2021. The presence of EUAs may discourage participation in relevant clinical trials, which delays the widespread implementation of evidenced‐based therapies. Large, robust RCTs should be completed, such as the RECOVERY trial in the United Kingdom, to quickly find the answers desperately required during a pandemic.

Abstract Background The majority of surgical wounds are closed (for example with sutures or staples) and so heal by primary intention. Where closure is not possible, or the wound subsequently breaks down, wounds may be left to heal from the bottom up (healing by secondary intention). Surgical wound healing by secondary intention (SWHSI) frequently presents a significant management challenge. Additional treatments are often required during the course of healing, and thus a significant financial burden is associated with treating these wounds. Increasingly, negative pressure wound therapy (NPWT) is used in the management of SWHSI. This wound dressing system provides a negative pressure (vacuum) to the wound, removing fluid into a canister, which is believed to be conducive to wound healing. Despite the increasing use of NPWT, there is limited robust evidence for the effectiveness of this device. A well-designed and conducted randomised controlled trial is now required to ascertain if NPWT is a clinically and cost-effective treatment for SWHSI. Methods SWHSI-2 is a pragmatic, multi-centre, cross surgical specialty, two arm, parallel group, randomised controlled superiority trial. Adult patients with a SWHSI will be randomised to receive either NPWT or usual care (no NPWT) and will be followed up for 12 months. The primary outcome will be time to healing (defined as full epithelial cover in absence of a scab) in number of days since randomisation. Secondary outcomes will include key clinical events (hospital admission or discharge, treatment status, reoperation, amputation, antibiotic use and death), wound infection, wound pain, health-related quality of life, health utility and resource use. Discussion Given the increasing use of NPWT, despite limited high-quality supporting evidence, the SWHSI-2 Trial will provide robust evidence on the clinical and cost-effectiveness of NPWT in the management of SWHSI. The SWHSI-2 Trial opened to recruitment in May 2019 and is currently recruiting across 20 participating centres. Trial registration ISRCTN 26277546 . Prospectively registered on 25 March 2019

Abstract 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, I 2 = 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)

Abstract 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.

Aims: A pragmatic multicentre randomized controlled trial, UK FROzen Shoulder Trial (UK FROST), was conducted in the UK NHS comparing the cost-effectiveness of commonly used treatments for adults with primary frozen shoulder in secondary care. Methods: A cost utility analysis from the NHS perspective was performed. Differences between manipulation under anaesthesia (MUA), arthroscopic capsular release (ACR), and early structured physiotherapy plus steroid injection (ESP) in costs (2018 GBP price base) and quality adjusted life years (QALYs) at one year were used to estimate the cost-effectiveness of the treatments using regression methods. Results: ACR was £1,734 more costly than ESP ((95% confidence intervals (CIs) £1,529 to £1,938)) and £1,457 more costly than MUA (95% CI £1,283 to £1,632). MUA was £276 (95% CI £66 to £487) more expensive than ESP. Overall, ACR had worse QALYs compared with MUA (-0.0293; 95% CI -0.0616 to 0.0030) and MUA had better QALYs compared with ESP (0.0396; 95% CI -0.0008 to 0.0800). At a £20,000 per QALY willingness-to-pay threshold, MUA had the highest probability of being cost-effective (0.8632) then ESP (0.1366) and ACR (0.0002). The results were robust to sensitivity analyses. Conclusion: While ESP was less costly, MUA was the most cost-effective option. ACR was not cost-effective. Cite this article: Bone Jt Open 2021;2(8):685–695.

Background: Poor response rates to follow-up questionnaires can adversely affect the progress of a randomised controlled trial and the validity of its results. This embedded ‘study within a trial’ aimed to investigate the impact of including a pen with the postal 3-month questionnaire completed by the trial participants on the response rates to this questionnaire. Methods: This study was a two-armed randomised controlled trial nested in the Gentle Years Yoga (GYY) trial. Participants in the intervention group of the GYY trial were allocated 1:1 using simple randomisation to either receive a pen (intervention) or no pen with their 3-month questionnaire (control). The primary outcome was the proportion of participants sent a 3-month questionnaire who returned it. Secondary outcomes were time taken to return the questionnaire, proportion of participants sent a reminder to return the questionnaire, and completeness of the questionnaire. Binary outcomes were analysed using logistic regression, time to return by Cox Proportional hazards regression and number of items completed by linear regression. Results: There were 111 participants randomised to the pen group and 118 to the no pen group who were sent a 3-month questionnaire. There was no evidence of a difference in return rates between the two groups (pen 107 (96.4%), no pen 117 (99.2%); OR 0.23, 95% CI 0.02 to 2.19, p=0.20). Furthermore, there was no evidence of a difference between the two groups in terms of time to return the questionnaire (HR 0.90, 95% CI 0.69 to 1.18, p=0.47), the proportion of participants sent a reminder (OR 0.85, 95% CI 0.48 to 1.53, p=0.60) nor the number of items completed (mean difference 0.51, 95% CI -0.04 to 1.06, p=0.07). Conclusion: The inclusion of a pen with the postal 3-month follow-up questionnaire did not have a statistically significant effect on response rate.

Aims: A pilon fracture is a severe ankle joint injury caused by high-energy trauma, typically affecting men of working age. Although relatively uncommon (5% to 7% of all tibial fractures), this injury causes among the worst functional and health outcomes of any skeletal injury, with a high risk of serious complications and long-term disability, and with devastating consequences on patients’ quality of life and financial prospects. Robust evidence to guide treatment is currently lacking. This study aims to evaluate the clinical and cost-effectiveness of two surgical interventions that are most commonly used to treat pilon fractures. Methods: A randomized controlled trial (RCT) of 334 adult patients diagnosed with a closed type C pilon fracture will be conducted. Internal locking plate fixation will be compared with external frame fixation. The primary outcome and endpoint will be the Disability Rating Index (a patient self-reported assessment of physical disability) at 12 months. This will also be measured at baseline, three, six, and 24 months after randomization. Secondary outcomes include the Olerud and Molander Ankle Score (OMAS), the five-level EuroQol five-dimenison score (EQ-5D-5L), complications (including bone healing), resource use, work impact, and patient treatment preference. The acceptability of the treatments and study design to patients and health care professionals will be explored through qualitative methods. Discussion: The two treatments being compared are the most commonly used for this injury, however there is uncertainty over which is most clinically and cost-effective. The Articular Pilon Fracture (ACTIVE) Trial is a sufficiently powered and rigorously designed study to inform clinical decisions for the treatment of adults with this injury. Cite this article: Bone Jt Open 2021;2(3):150–163.

Abstract Background This article reports the results from a feasibility study of an intervention (‘E-PLAYS’) aimed at supporting children who experience difficulties with social communication. E-PLAYS is based around a dyadic computer game, which aims to develop collaborative and communication skills. A pilot study found that when E-PLAYS was delivered by researchers, improvements on communication test scores and on collaborative behaviours were observed. The aim of this study was to ascertain the feasibility of running a full-scale trial to test the effectiveness of E-PLAYS in a National Health Service (NHS) setting with delivery by speech and language therapists and teaching assistants. Methods The study was a two-arm feasibility cluster-randomised controlled trial of the E-PLAYS intervention with a treatment as usual control arm. Data relating to recruitment and retention, treatment fidelity, acceptability to participants, suitability of outcomes and feasibility of collecting health economic measures and of determining cost-effectiveness were collected. Speech and language therapists selected suitable children (ages 4–7 years old) from their caseload. E-PLAYS intervention (experimental group) was then delivered by teaching assistants overseen by speech and language therapists. The control group received usual care. Assessments included blinded language measures and observations, non-blinded teacher-reported measures of peer relations and classroom behaviour and non-blinded parent-reported use of health and education resources and quality of life. Results Planned recruitment was for 70 children, in the event, 50 children were recruited which was sufficient for feasibility purposes. E-PLAYS was very highly rated by children, teaching assistants and speech and language therapists and treatment fidelity did not pose any issues. We were able to collect health economic data which suggests that E-PLAYS would be a low-cost intervention. Conclusion Based on recruitment, retention and adherence rates and our outcome measures, a full-scale randomised controlled trial estimated appears feasible and warranted to assess the effectiveness of E-PLAYS for use by the NHS and schools. Trial registration ISRCTN 14818949 (retrospectively registered).

Abstract Background Ensuring fidelity to complex interventions is a challenge when conducting pragmatic randomised controlled trials. We explore fidelity through a qualitative process evaluation, which was conducted alongside a pragmatic, multicentre, two-arm cohort randomised controlled trial: the REFORM (Reducing Falls with Orthoses and a Multifaceted podiatry intervention) trial. The paper aims, through a qualitative process evaluation, to explore some of the factors that may have affected the delivery of the REFORM intervention and highlight how project-specific fidelity can be assessed using a truly mixed-methods approach when informed by qualitative insights. Design Semi-structured qualitative interviews carried out as part of a process evaluation. Interviews were analysed thematically. Setting Seven NHS trusts in the UK and a University podiatry school in Ireland. Interviews were undertaken face-to-face or over the telephone. Participants Twenty-one REFORM trial participants and 14 podiatrists who delivered the REFORM intervention. Results Factors affecting fidelity included: how similar the intervention was to routine practice; the challenges of delivering a multifaceted intervention to a heterogeneous older population; and practical issues with delivery such as time and training. Trial participants’ views of the intervention, whether falls prevention is a personal priority, their experience of being part of a trial and individual factors such as medical conditions may also have affected intervention fidelity. Conclusions Our process evaluation highlighted factors that were perceived to have affected the fidelity of the REFORM intervention and in doing so demonstrates the importance of considering fidelity when designing and evaluating pragmatic trials. We propose a number of recommendations of how important project-specific insights from qualitative work can be incorporated into the design of fidelity measurement of future trials, which build on existing conceptual fidelity frameworks. In particular, we encourage adopting a mixed-methods approach whereby qualitative insights can be used to suggest ways to enhance quantitative data collection facilitating integration through hypothesis generation, hypothesis testing and seeking explanation for trial findings. This will provide a framework of enabling measures of fidelity to be incorporated into the understanding of trial results which has been relatively neglected by existing literature. Trial registration ISRCTN Registry: ISRCTN68240461 . Registered on 01/07/2011.

Abstract Background Eighty per cent of UK women have at least one baby, making pregnancy an opportunity to help women stop smoking before their health is irreparably compromised. Smoking cessation during pregnancy helps protect infants from miscarriage, still birth, low birth weight, asthma, attention deficit disorder and adult cardiovascular disease. UK national guidelines highlight lack of evidence for effectiveness of financial incentives to help pregnant smokers quit. This includes a research recommendation: within a UK context, are incentives an acceptable, effective and cost-effective way to help pregnant women who smoke to quit? Methods The Cessation in Pregnancy Incentives Trial (CPIT) III is a pragmatic, 42-month, multi-centre, parallel-group, individually randomised controlled superiority trial of the effect on smoking status of adding to usual Stop Smoking Services (SSS) support, the offer of up to £400 of financial voucher incentives, compared with usual support alone, to quit smoking during pregnancy. Participants (n = 940) are pregnant smokers (age > 16 years,

Abstract Background Measures shown to improve outcomes for patients often fail to be adopted into routine practice in the NHS. The Institute for Health Improvement Breakthrough Series Collaborative (BSC) model is designed to support implementation at scale. This trial aims to assess the effectiveness and cost-effectiveness of quality improvement collaboratives (QICs) based on the BSC method for introducing service improvements at scale in the NHS. Methods Forty Trusts will be randomised (1:1) to introduce one of two protocols already shown to improve outcomes in patients undergoing elective total hip and knee replacement surgery. The intervention is improvement collaboratives based on the BSC model, a learning system that brings together a large number of teams to seek improvement focussed on a proven intervention. Collaboratives aim to deliver at scale, maximise local engagement and leadership and are designed to build capacity, enable learning and prepare for sustainability. Collaboratives involve Learning Sessions, Action Periods, and a summative congress. Trusts will be supported to introduce either: decolonisation for Methicillin Sensitive Staphylococcus aureus (MSSA) to reduce post-operative infection (QIST: Infection), or an anaemia optimisation programme to reduce peri-operative blood transfusions (QIST: Anaemia). Trusts will continue with their usual practice for whichever protocol they are not introducing. Anonymised data related to both infection and anaemia outcomes for patients undergoing hip or knee arthroplasty at all sites will mean that the two groups act as controls for each other. The primary outcome for the QIST: Infection collaborative is deep MSSA surgical site infection within 90 days of surgery, and for the QIST: Anaemia collaborative is blood transfusion within 7 days of surgery. Patient-level secondary outcomes include length of hospital stay and readmission, which will also inform the economic costings. Qualitative interviews will evaluate the support provided to teams. Discussion The scale of this trial brings considerable challenges and potential barriers to delivery. Anticipated challenges relate to recruiting and sustaining up to 40 organisations, each with its own culture and context. This complex project with multiple stakeholders across a large geographical area will be managed by experienced senior-level project leaders with a proven track record in advanced project management. The team should ensure effective project governance and communications. Trial registration ISRCTN, ISRCTN11085475. Prospectively registered on 15 February 2018.

Abstract The evidence base available to trialists to support trial process decisions—e.g. how best to recruit and retain participants, how to collect data or how to share the results with participants—is thin. One way to fill gaps in evidence is to run Studies Within A Trial, or SWATs. These are self-contained research studies embedded within a host trial that aim to evaluate or explore alternative ways of delivering or organising a particular trial process. SWATs are increasingly being supported by funders and considered by trialists, especially in the UK and Ireland. At some point, increasing SWAT evidence will lead funders and trialists to ask: given the current body of evidence for a SWAT, do we need a further evaluation in another host trial? A framework for answering such a question is needed to avoid SWATs themselves contributing to research waste. This paper presents criteria on when enough evidence is available for SWATs that use randomised allocation to compare different interventions.

Abstract Aims Morphine is shown to relieve chronic breathlessness in chronic obstructive pulmonary disease. There are no definitive data in people with heart failure. We aimed to determine the effectiveness and cost‐effectiveness of 12 weeks morphine therapy for the relief of chronic breathlessness in people with chronic heart failure compared with placebo. Methods and results Parallel group, double‐blind, randomized, placebo‐controlled, phase III trial of 20 mg daily oral modified release morphine was conducted in 13 sites in England and Scotland: hospital/community cardiology or palliative care outpatients. The primary analysis compared between‐group numerical rating scale average breathlessness/24 hours at week 4 using a covariance pattern linear mixed model. Secondary outcomes included treatment‐emergent harms (worse or new). The trial closed early due to slow recruitment, randomizing 45 participants [average age 72 (range 39–89) years; 84% men; 98% New York Heart Association class III]. For the primary analysis, the adjusted mean difference was 0.26 (95% confidence interval, −0.86 to 1.37) in favour of placebo. All other breathlessness measures improved in both groups (week 4 change‐from‐baseline) but by more in those assigned to morphine. Neither group was excessively drowsy at baseline or week 4. There were no between‐group differences in quality of life (Kansas) or cognition (Montreal) at any time point. There was no exercise‐related desaturation and no change between baseline and week 4 in either group. There was no change in vital signs at week 4. The natriuretic peptide measures fell in both groups but by more in the morphine group [morphine 2169 (1092, 3851) pg/mL vs. placebo 2851 (1694, 5437)] pg/mL. There was no excess serious adverse events in the morphine group. Treatment‐emergent harms during the first week were more common in the morphine group; all apart from 1 were ≤ grade 2. Conclusions We could not answer our primary objectives due to inadequate power. However, we provide novel placebo‐controlled medium‐term benefit and safety data useful for clinical practice and future trial design. Morphine should only be prescribed in this population when other measures are unhelpful and with early management of side effects.

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.

Abstract Background One of the top three research priorities for the UK clinical trial community is to address the gap in evidence-based approaches to improving participant retention in randomised trials. Despite this, there is little evidence supporting methods to improve retention. This paper reports the PRioRiTy II project, a Priority Setting Partnership (PSP) that identified and prioritised unanswered questions and uncertainties around trial retention in collaboration with key stakeholders. Methods This PSP was conducted in collaboration with the James Lind Alliance, a non-profit making initiative, to support key stakeholders (researchers, patients, and the public) in jointly identifying and agreeing on priority research questions. There were three stages. (1) First an initial online survey was conducted consisting of six open-ended questions about retention in randomised trials. Responses were coded into thematic groups to create a longlist of questions. The longlist of questions was checked against existing evidence to ensure that they had not been answered by existing research. (2) An interim stage involved a further online survey where stakeholders were asked to select questions of key importance from the longlist. (3) A face-to-face consensus meeting was held, where key stakeholder representatives agreed on an ordered list of 21 unanswered research questions for methods of improving retention in randomised trials. Results A total of 456 respondents yielded 2431 answers to six open-ended questions, from which 372 questions specifically about retention were identified. Further analysis included thematically grouping all data items within answers and merging questions in consultation with the Steering Group. This produced 27 questions for further rating during the interim survey. The top 21 questions from the interim online survey were brought to a face-to-face consensus meeting in which key stakeholder representatives prioritised the order. The ‘Top 10’ of these are reported in this paper. The number one ranked question was ’What motivates a participant’s decision to complete a clinical trial?’ The entire list will be available at www.priorityresearch.ie. Conclusion The Top 10 list can inform the direction of future research on trial methods and be used by funders to guide projects aiming to address and improve retention in randomised trials.

Abstract Background Surgeon and patient treatment preferences are important threats to the internal and external validity of surgical trials such as PROFHER, which compared surgical versus non-surgical treatment for displaced fractures of the proximal humerus in adults. We explored the treatment preferences expressed by surgeons and patients in the trial and how these impacted on patient selection, trial conduct and patient outcome. Methods A series of exploratory secondary analyses of the PROFHER trial data were undertaken. We reviewed the extent of surgeon and patient treatment preferences (surgery or not surgery) at screening (n = 1250) as well as prior preference (including no preference) of randomised patients (n = 250), and assessed their impact on recruitment and adherence to follow-up and rehabilitation. Changes in treatment after 2 years’ follow-up were explored. Patient preference and characteristics associated with trial inclusion or treatment preference (t test, chi-squared test, Wilcoxon rank-sum test) were included as treatment interaction terms in the primary trial analysis of shoulder functioning (Oxford Shoulder Score, OSS). Results Surgeons excluded 17% of otherwise eligible patients based on lack of equipoise; these patients had less complex fractures (p

Abstract Background Almost one-half of 12–15 year olds living in deprived areas of the UK have dental caries (tooth decay) with few oral health promotion programmes aimed at children of this age. Mobile phone-based interventions such as short messaging service (SMS) interventions have been found effective at changing certain behaviours and improving health outcomes. This protocol describes the BRIGHT Trial, investigating the clinical and cost-effectiveness of a behaviour change intervention—classroom-based session (CBS) embedded in the curriculum and a series of SMS delivered to participants twice daily to remind them to brush their teeth, compared to usual curriculum and no SMS—to reduce the prevalence of dental caries in young people from deprived areas. Objectives To investigate the clinical and cost-effectiveness of a complex intervention to improve the oral health of young people living in deprived areas. Methods/design This is a school-based, assessor-blinded, two-arm cluster-randomised controlled trial with an internal pilot trial. Overall, the trial will involve approximately 5040 11–13 year olds in 42 schools with a 3-year follow-up. The trial will take place in secondary schools in England, Scotland and Wales. The primary outcome is the presence of carious lesions in permanent teeth at 3 years. Secondary outcomes are: number of carious teeth, frequency of twice-daily toothbrushing, plaque levels, gingivitis, child health-related quality of life and oral health-related quality of life. A cost-utility analysis will be conducted. Discussion The findings of the trial have implications for embedding oral health interventions into school curricula guidance produced by national bodies, including departments for education and dental public health and guideline-development organisations. Trial registration ISRCTN registry, ISRCTN12139369. Registered on 10 May 2017.

Abstract 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 proposal presented in this article describes a feasibility study for a trial to test an intervention (‘E-PLAYS’) aimed at supporting children with social communication impairments. E-PLAYS harnesses technology in the form of a novel computer game in order to develop collaborative and communication skills. Preliminary studies by the authors show that when E-PLAYS was administered by the research team, children with social communication impairments showed improvements on communication test scores and on observed collaborative behaviours. The study described here is a pragmatic trial to test the application of E-PLAYS delivered by NHS speech and language therapists together with schools. Methods This protocol outlines a two-arm feasibility cluster-randomised controlled trial of the E-PLAYS intervention with treatment as usual control arm, with randomisation at the level of the speech and language therapist. The aim of this study is to ascertain whether it will be feasible to progress to running a full-scale definitive trial to test the effectiveness of E-PLAYS in an NHS setting. Data relating to recruitment and retention, the appropriateness of outcomes and the acceptability of E-PLAYS to participants will be collected. Speech and language therapists will select suitable children (ages 4–7 years old) from their caseloads and deliver either the E-PLAYS intervention (experimental group) or treatment as usual (control group). Assessments will include blinded language measures and observations, non-blinded teacher-reported measures of peer relations and classroom behaviour and parent-reported use of resources and quality of life. There will also be a qualitative process evaluation. Discussion The findings of this study will inform the decision as to whether to progress to a full-scale definitive randomised controlled trial to test the effectiveness of E-PLAYS when delivered by speech and language therapists and 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. Trial registration ISRCTN 14818949 (retrospectively registered).

Abstract Background Smoking in pregnancy is a major international public health problem. Self-help support (SHS) increases the likelihood of women stopping smoking in pregnancy and delivering this kind of support by text message could be a cost-effective way to deliver SHS to pregnant women who smoke. SHS delivered by text message helps non-pregnant smokers to stop but the currently available message programmes are not appropriate for use in pregnancy. A randomised controlled trial (RCT) has demonstrated the feasibility and acceptability of using a programme called ‘MiQuit’ to text SHS support to pregnant women who smoke. Another pilot RCT has shown that it would be feasible to run a larger, multi-centre trial within the UK National Health Service (NHS). The aim of this third RCT is to complete MiQuit’s evaluation, demonstrating whether or not this is efficacious for smoking cessation in pregnancy. Methods/design This is a multi-centre, parallel-group RCT. Pregnant women aged over 16 years, of less than 25 weeks’ gestation who smoke one or more daily cigarettes but smoked at least five daily cigarettes before pregnancy and who understand written English and are being identified in 24 English antenatal care hospitals. Participants are randomised to control or intervention groups in a 1:1 ratio stratified by gestation (

Abstract Background Randomised controlled trials are considered the best method for determining the effectiveness and safety of health interventions. Trials involving children are essential to ensure that treatments are safe and effective. However, many trials, in both adult and paediatric populations, do not achieve recruitment targets and/or maintain retention of participants, which can lead to a reduction in the internal and external validity of the results. Identifying ways of improving trial efficiency are important in order to increase the successful completion of trials. Main body A ‘Study Within A Trial’ (SWAT) is a self-contained study embedded within an ongoing trial, which aims to establish evidence to improve the management and delivery of trials in healthcare. Increasing numbers of SWATs have been undertaken in recent years yet very few within paediatric trials. Herein, we describe some of the challenges with undertaking a programme of SWATs within paediatric clinical trials in the UK. The TRECA (TRials Engagement in Children and Adolescents) study involves developing multimedia websites for use within paediatric trials to provide recruitment information to children, young people and their families about the clinical trial. Challenges encountered included governance issues such as host trial approval processes and sharing of anonymised data, funding issues for host trials, internet quality and accessibility within the healthcare setting, and ethical concerns associated with SWAT methodology. We believe the ethical concerns are more pronounced in the paediatric setting, perhaps because of the fewer SWATs undertaken in these settings or that a more cautious, risk-averse approach to undertaking research with children is taken. Conclusion SWATs are becoming increasingly common to provide an evidence base for methods to improve trial efficiency. However, we encountered a number of unanticipated challenges to embedding TRECA that have not been previously reported within the scientific literature. We believe that, if these issues were addressed through wider promotion and explanation of undertaking SWATs involving all key stakeholders, as well as by exploration of alternative funding models for SWATs, this would enable more streamlined, appropriate and timely processes for SWATs and a stronger evidence base for what works to increase trial efficiency. Trial registration The TRECA study is registered on ISRCTN, ID 73136092. Registered on 24 August 2016.

Objectives Randomised controlled trials conducted using cohorts and routinely collected data, including registries, electronic health records and administrative databases, are increasingly used in healthcare intervention research. A Consolidated Standards of Reporting Trials (CONSORT) statement extension for trials conducted using cohorts and routinely collected data (CONSORT-ROUTINE) has been developed with the goal of improving reporting quality. This article describes the processes and methods used to develop the extension and decisions made to arrive at the final checklist.Methods The development process involved five stages: (1) identification of the need for a reporting guideline and project launch; (2) conduct of a scoping review to identify possible modifications to CONSORT 2010 checklist items and possible new extension items; (3) a three-round modified Delphi study involving key stakeholders to gather feedback on the checklist; (4) a consensus meeting to finalise items to be included in the extension, followed by stakeholder piloting of the checklist; and (5) publication, dissemination and implementation of the final checklist.Results 27 items were initially developed and rated in Delphi round 1, 13 items were rated in round 2 and 11 items were rated in round 3. Response rates for the Delphi study were 92 of 125 (74%) invited participants in round 1, 77 of 92 (84%) round 1 completers in round 2 and 62 of 77 (81%) round 2 completers in round 3. Twenty-seven members of the project team representing a variety of stakeholder groups attended the in-person consensus meeting. The final checklist includes five new items and eight modified items. The extension Explanation & Elaboration document further clarifies aspects that are important to report.Conclusion Uptake of CONSORT-ROUTINE and accompanying Explanation & Elaboration document will improve conduct of trials, as well as the transparency and completeness of reporting of trials conducted using cohorts and routinely collected data.

Background: Frozen shoulder causes pain and stiffness. It affects around 10% of people in their fifties and is slightly more common in women. Costly and invasive surgical interventions are used, without high-quality evidence that these are effective. Objectives: To compare the clinical effectiveness and cost-effectiveness of three treatments in secondary care for adults with frozen shoulder; to qualitatively explore the acceptability of these treatments to patients and health-care professionals; and to update a systematic review to explore the trial findings in the context of existing evidence for the three treatments. Design: This was a pragmatic, parallel-group, multicentre, open-label, three-arm, randomised superiority trial with unequal allocation (2 : 2 : 1). An economic evaluation and a nested qualitative study were also carried out. Setting: The orthopaedic departments of 35 hospitals across the UK were recruited from April 2015, with final follow-up in December 2018. Participants: Participants were adults (aged ≥ 18 years) with unilateral frozen shoulder, characterised by restriction of passive external rotation in the affected shoulder to

Background: Scaphoid fractures account for 90% of carpal fractures and occur predominantly in young men. Immediate surgical fixation of this fracture has increased. Objective: To compare the clinical effectiveness and cost-effectiveness of surgical fixation with cast treatment and early fixation in adults with scaphoid waist fractures that fail to unite. Design: Multicentre, pragmatic, open-label, parallel two-arm randomised controlled trial with an economic evaluation and a nested qualitative study. Setting: Orthopaedic departments of 31 hospitals in England and Wales recruited from July 2013, with final follow-up in September 2017. Participants: Adults (aged ≥ 16 years) presenting within 2 weeks of injury with a clear, bicortical fracture of the scaphoid waist on plain radiographs. Interventions: Early surgical fixation using Conformité Européenne-marked headless compression screws. Below-elbow cast immobilisation for 6–10 weeks and urgent fixation of confirmed non-union. Main outcome measures: The primary outcome and end point was the Patient-Rated Wrist Evaluation total score at 52 weeks, with a clinically relevant difference of 6 points. Secondary outcomes included Patient-Rated Wrist Evaluation pain and function subscales, Short Form questionnaire 12-items, bone union, range of movement, grip strength, complications and return to work. Results: The mean age of 439 participants was 33 years; 363 participants were male (83%) and 269 participants had an undisplaced fracture (61%). The primary analysis was on 408 participants with valid Patient-Rated Wrist Evaluation outcome data for at least one post-randomisation time point (surgery, n = 203 of 219; cast, n = 205 of 220). There was no clinically relevant difference in the Patient-Rated Wrist Evaluation total score at 52 weeks: the mean score in the cast group was 14.0 (95% confidence interval 11.3 to 16.6) and in the surgery group was 11.9 (95% confidence interval 9.2 to 14.5), with an adjusted mean difference of –2.1 in favour of surgery (95% confidence interval –5.8 to 1.6; p = 0.27). The non-union rate was low (surgery group, n = 1; cast group, n = 4). Eight participants in the surgery group had a total of 11 reoperations and one participant in the cast group required a reoperation for non-union. The base-case economic analysis at 52 weeks found that surgery cost £1295 per patient more (95% confidence interval £1084 to £1504) than cast treatment. The base-case analysis of a lifetime-extrapolated model confirmed that the cast treatment pathway was more cost-effective. The nested qualitative study identified patients’ desire to have a ‘sense of recovering’, which surgeons should address at the outset. Limitation: There were 17 participants who had initial cast treatment and surgery for confirmed non-union, which in 14 cases was within 6 months from randomisation and in three cases was after 6 months. Three of the four participants in the cast group who had a non-union at 52 weeks were not offered surgery. Conclusions: Adult patients with an undisplaced or minimally displaced scaphoid waist fracture should have cast immobilisation and suspected non-unions immediately confirmed and urgently fixed. Patients should be followed up at 5 years to investigate the effect of partial union, degenerative arthritis, malunion and screw problems on their quality of life. Trial registration: Current Controlled Trials ISRCTN67901257. 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. 24, No. 52. See the NIHR Journals Library website for further project information.

Background: Most surgical incisions heal by primary intention (i.e. wound edges are apposed with sutures, clips or glue); however, some heal by secondary intention (i.e. the wound is left open and heals by formation of granulation tissue). There is, however, a lack of evidence regarding the epidemiology, management and impact on patients’ quality of life of these surgical wounds healing by secondary intention, resulting in uncertainty regarding effective treatments and difficulty in planning care and research. Objectives: To derive a better understanding of the nature, extent, costs, impact and outcomes of surgical wounds healing by secondary intention, effective treatments, and the value and nature of further research. Design: Cross-sectional survey; inception cohort; cost-effectiveness and value of implementation analyses; qualitative interviews; and pilot, feasibility randomised controlled trial. Setting: Acute and community care settings in Leeds and Hull, Yorkshire, UK. Participants: Adults (or for qualitative interviews, patients or practitioners) with previous experience of a surgical wound healing by secondary intention. Inclusion criteria varied between the individual workstreams. Interventions: The pilot, feasibility randomised controlled trial compared negative-pressure wound therapy – a device applying a controlled vacuum to a wound via a dressing – with usual care (no negative-pressure wound therapy). Results: Survey data estimated that treated surgical wounds healing by secondary intention have a point prevalence of 4.1 per 10,000 population (95% confidence interval 3.5 to 4.7 per 10,000 population). Surgical wounds healing by secondary intention most frequently occurred following colorectal surgery (n = 80, 42.8% cross-sectional survey; n = 136, 39.7% inception cohort) and were often planned before surgery (n = 89, 47.6% cross-sectional survey; n = 236, 60.1% inception cohort). Wound care was frequently delivered in community settings (n = 109, 58.3%) and most patients (n = 184, 98.4%) received active wound treatment. Cohort data identified hydrofibre dressings (n = 259, 65.9%) as the most common treatment, although 29.3% (n = 115) of participants used negative-pressure wound therapy at some time during the study. Surgical wounds healing by secondary intention occurred in 81.4% (n = 320) of participants at a median of 86 days (95% confidence interval 75 to 103 days). Baseline wound area (p ≤ 0.01), surgical wound contamination (determined during surgery; p = 0.04) and wound infection at any time (p ≤ 0.01) (i.e. at baseline or postoperatively) were found to be predictors of prolonged healing. Econometric models, using observational, cohort study data, identified that, with little uncertainty, negative-pressure wound therapy treatment is more costly and less effective than standard dressing treatment for the healing of open surgical wounds. Model A (ordinary least squares with imputation) effectiveness: 73 days longer than those who did not receive negative-pressure wound therapy (95% credible interval 33.8 to 112.8 days longer). Model A cost-effectiveness (associated incremental quality-adjusted life-years): observables –0.012 (standard error 0.005) and unobservables –0.008 (standard error 0.011). Model B (two-stage model, logistic and linear regression) effectiveness: 46 days longer than those who did not receive negative-pressure wound therapy (95% credible interval 19.6 to 72.5 days longer). Model B cost-effectiveness (associated incremental quality-adjusted life-years): observables –0.007 (standard error 0.004) and unobservables –0.027 (standard error 0.017). Patient interviews (n = 20) identified initial reactions to surgical wounds healing by secondary intention of shock and disbelief. Impaired quality of life characterised the long healing process, with particular impact on daily living for patients with families or in paid employment. Patients were willing to try any treatment promising wound healing. Health professionals (n = 12) had variable knowledge of surgical wound healing by secondary intention treatments and, frequently, favoured negative-pressure wound therapy, despite the lack of robust evidence. The pilot feasibility randomised controlled trial screened 248 patients for eligibility and subsequently recruited and randomised 40 participants to receive negative-pressure wound therapy or usual care (no negative-pressure wound therapy). Data indicated that it was feasible to complete a full randomised controlled trial to provide definitive evidence for the clinical effectiveness and cost-effectiveness of negative-pressure wound therapy as a treatment for surgical wounds healing by secondary intention. Key elements and recommendations for a larger randomised controlled trial were identified. Limitations: This research programme was conducted in a single geographical area (i.e. Yorkshire and the Humber, UK) and local guidelines and practices may have affected treatment availability, and so may not represent UK-wide treatment choices. A wide range of wound types were included; however, some wound types may be under-represented, meaning that this research may not represent the overall surgical wound healing by secondary intention population. The lack of randomised controlled trial data on the relative effects of negative-pressure wound therapy in surgical wounds healing by secondary intention resulted in much of the economic modelling being based on observational data. Observational data, even with extensive adjustment, do not negate the potential for unresolved confounding to affect the results, which can reduce confidence in conclusions drawn from observational data. Definitive evidence from a randomised controlled trial may be the only way to overcome this lack of confidence. Conclusions: This research has provided new information regarding the nature, extent, costs, impacts and outcomes of surgical wounds healing by secondary intention, treatment effectiveness, and the value and nature of future research, while addressing previous uncertainties regarding the problem of surgical wounds healing by secondary intention. Aspects of our research indicate that negative-pressure wound therapy is more costly and less effective than standard dressing for the healing of open surgical wounds. However, because this conclusion is based solely on observational data, it may be affected by unresolved confounding. Should a future randomised controlled trial be considered necessary, its design should reflect careful consideration of the findings of this programme of research. Future work: This research signals the importance of further research on surgical wound healing by secondary intention. Key research questions raised by this programme of research include (1) which treatments are clinically effective and cost-effective for surgical wound healing by secondary intention for all patients or for particular patient subgroups? (2) Can particular prognostic factors predict time to healing of surgical wound healing by secondary intention? And (3) do psychosocial interventions have the potential to improve quality of life in people with hard-to-heal surgical wound healing by secondary intention? Given that negative-pressure wound therapy has been widely adopted, with relatively little evidence to support its use, the design and outcomes of a randomised controlled trial would need to be carefully considered. We focused in this research on wound healing, and maintain, based on the findings of patient interviews, that this is a key outcome for future research. Impacts of negative-pressure wound therapy on outcomes such as infection and reoperation should also be considered, as should patients’ views of the treatment. The type of patient group recruited and the outcomes of interest will all influence the duration of follow-up of any planned study. The comparator in any future study will also need careful consideration. Trial registration: Current Controlled Trials ISRCTN12761776. Funding: This project was funded by the National Institute for Health Research Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 8, No. 7. See the National Institute for Health Research Journals Library website for further project information.

Background: Printed participant information about randomised controlled trials is often long, technical and difficult to navigate. Improving information materials is possible through optimisation and user-testing, and may impact on participant understanding and rates of recruitment. Methods: A study within a trial (SWAT) was undertaken within the CASPER trial. Potential CASPER participants were randomised to receive either the standard trial information or revised information that had been optimised through information design and user testing. Results: A total of 11,531 patients were randomised in the SWAT. Rates of recruitment to the CASPER trial were 2.0% in the optimised information group and 1.9% in the standard information group (odds ratio 1.027; 95% CI 0.79 to 1.33; p=0.202). Conclusions: Participant information that had been optimised through information design and user testing did not result in any change to rate of recruitment to the host trial. Registration: ISRCTN ID ISRCTN02202951; registered on 3 June 2009.

Abstract Background Randomized controlled trials (RCTs) are often complex and expensive to perform. Less than one third achieve planned recruitment targets, follow-up can be labor-intensive, and many have limited real-world generalizability. Designs for RCTs conducted using cohorts and routinely collected health data, including registries, electronic health records, and administrative databases, have been proposed to address these challenges and are being rapidly adopted. These designs, however, are relatively recent innovations, and published RCT reports often do not describe important aspects of their methodology in a standardized way. Our objective is to extend the Consolidated Standards of Reporting Trials (CONSORT) statement with a consensus-driven reporting guideline for RCTs using cohorts and routinely collected health data. Methods The development of this CONSORT extension will consist of five phases. Phase 1 (completed) consisted of the project launch, including fundraising, the establishment of a research team, and development of a conceptual framework. In phase 2, a systematic review will be performed to identify publications (1) that describe methods or reporting considerations for RCTs conducted using cohorts and routinely collected health data or (2) that are protocols or report results from such RCTs. An initial “long list” of possible modifications to CONSORT checklist items and possible new items for the reporting guideline will be generated based on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) and The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statements. Additional possible modifications and new items will be identified based on the results of the systematic review. Phase 3 will consist of a three-round Delphi exercise with methods and content experts to evaluate the “long list” and generate a “short list” of key items. In phase 4, these items will serve as the basis for an in-person consensus meeting to finalize a core set of items to be included in the reporting guideline and checklist. Phase 5 will involve drafting the checklist and elaboration-explanation documents, and dissemination and implementation of the guideline. Discussion Development of this CONSORT extension will contribute to more transparent reporting of RCTs conducted using cohorts and routinely collected health data.

Abstract To understand the full extent of the impact of a trial, it is important to consider the long-term consequences of outcomes beyond the trial follow-up period, especially for early year’s interventions. A systematic review of the literature associated with the long-term consequences of four key outcomes from the Building Blocks trial, specifically, low birth weight, smoking during pregnancy, interval to subsequent pregnancy and A&E attendance or inpatient admission was conducted. These factors were guided by the funders, the Department of Health, as being of particular interest in the UK context. Relevant studies were identified from a number of sources including large databases, reference checking and citation searching. The search yielded 3665 papers, 43 of which were considered appropriate for inclusion. Of these, 29 were relating to smoking during pregnancy, 13 to low birth weight, 0 to A&E attendances during early childhood and 1 to short (

Abstract Background There has been an increased drive towards Evidence Based Policing in recent years. Unlike in other public sector services, such as health and education, randomised controlled trials in the police setting are relatively rare. This paper discusses some of the methodological and practical challenges of conducting a randomised controlled trial in the police setting in the UK, based on our experience of the Connect trial. This pragmatic, cluster-randomised controlled trial investigated the effectiveness of a face-to-face training intervention for frontline officers in comparison to routine training. The primary outcome was the number of incidents which resulted in a police response reported to North Yorkshire Police control room in a 1-month period up to 6 months after delivery of training. Main text The methodological and practical challenges that we experienced whilst conducting the Connect trial are discussed under six headings: establishing the unit of randomisation; population of interest and sample size; co-production of evidence; time frame; outcomes; and organisational issues. Conclusion Recommendations on the conduct of future randomised controlled trials in the police setting are made. To understand the context in which research is undertaken, collaboration between police and academia is needed and police officers should be embedded within trial management groups. Engagement with police data analysts to understand what data is available and facilitate obtaining trial data is also recommended. Police forces may wish to review their IT systems and recording practices. Pragmatic trials are encouraged and time frames need to allow for trial set-up and obtaining relevant ethical approvals. Trial registration ISRCTN Registry, ID: ISRCTN11685602 . Retrospectively registered on 13 May 2016.

Abstract Background This study sought to establish the preferences of people with Rheumatoid Arthritis (RA) about the best outcome measure for a health and fitness intervention randomised controlled trial (RCT). The results of this study were used to inform the choice of the trial primary and secondary outcome measure. Methods A discrete choice experiment (DCE) was used to assess people’s preferences regarding a number of outcomes (foot and ankle pain, fatigue, mobility, ability to perform daily activities, choice of footwear) as well as different schedules and frequency of delivery for the health and fitness intervention. The outcomes were chosen based on literature review, clinician recommendation and patients’ focus groups. The DCE was constructed in SAS software using the D-efficiency criteria. It compared hypothetical scenarios with varying levels of outcomes severity and intervention schedule. Preference weights were estimated using appropriate econometric models. The partial log-likelihood method was used to assess the attribute importance. Results One hundred people with RA completed 18 choice sets. Overall, people selected foot and ankle pain as the most important outcome, with mobility being nearly as important. There was no evidence of differential preference between intervention schedules or frequency of delivery. Conclusions Foot and ankle pain can be considered the patient choice for primary outcome of an RCT relating to a health and fitness intervention. This study demonstrated that, by using the DCE method, it is possible to incorporate patients’ preferences at the design stage of a RCT. This approach ensures patient involvement at early stages of health care design.

Abstract Background Frozen shoulder (also known as adhesive capsulitis) occurs when the capsule, or the soft tissue envelope around the ball and socket shoulder joint, becomes scarred and contracted, making the shoulder tight, painful and stiff. It affects around 1 in 12 men and 1 in 10 women of working age. Although this condition can settle with time (typically taking 1 to 3 years), for some people it causes severe symptoms and needs referral to hospital. Our aim is to evaluate the clinical and cost-effectiveness of two invasive and costly surgical interventions that are commonly used in secondary care in the National Health Service (NHS) compared with a non-surgical comparator of Early Structured Physiotherapy. Methods We will conduct a randomised controlled trial (RCT) of 500 adult patients with a clinical diagnosis of frozen shoulder, and who have radiographs that exclude other pathology. Early Structured Physiotherapy with an intra-articular steroid injection will be compared with manipulation under anaesthesia with a steroid injection or arthroscopic (keyhole) capsular release followed by manipulation. Both surgical interventions will be followed with a programme of post-procedural physiotherapy. These treatments will be undertaken in NHS hospitals across the United Kingdom. The primary outcome and endpoint will be the Oxford Shoulder Score (a patient self-reported assessment of shoulder function) at 12 months. This will also be measured at baseline, 3 and 6 months after randomisation; and on the day that treatment starts and 6 months later. Secondary outcomes include the Disabilities of Arm Shoulder and Hand (QuickDASH) score, the EQ-5D-5 L score, pain, extent of recovery and complications. We will explore the acceptability of the different treatments to patients and health care professionals using qualitative methods. Discussion The three treatments being compared are the most frequently used in secondary care in the NHS, but there is uncertainty about which one works best and at what cost. UK FROST is a rigorously designed and adequately powered study to inform clinical decisions for the treatment of this common condition in adults. Trial registration International Standard Randomised Controlled Trial Register, ID: ISRCTN48804508 . Registered on 25 July 2014.