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The RECOVERY trial assessed the effectiveness of treatments on preventing severe outcomes from COVID-19 disease in hospitalised patients from 176 NHS hospitals. Clinical benefits of Dexamethasone were observed for hospitalised COVID-19 patients. About 15% of all eligible patients were recruited into the trial. Had patient recruitment been higher the study would have been completed more rapidly. To estimate the cost-effectiveness of improving recruitment to the RECOVERY trial from 15% to 50%, by employing or redeploying two research nurses to each hospital participating in the RECOVERY trial. The analysis is restricted to the evaluation of Dexamethasone versus No Dexamethasone. A decision tree model was developed to estimate the cost-effectiveness of Dexamethasone, against No Dexamethasone. Probability, utility, and cost inputs were used for each pathway and treatment. Then, a cost-utility analysis of clinical practice post-RECOVERY trial (83% Dexamethasone, 17% No Dexamethasone) versus previous clinical practice (100% No Dexamethasone) was undertaken; this analysis was aggregated at the population level and the cost of employing or redeploying two research nurses at each hospital was added, to estimate the cost-effectiveness of faster recruitment to the RECOVERY trial. Faster recruitment to the RECOVERY trial could have generated an incremental net benefit of £13,955,476 related to the evaluation of Dexamethasone against No Dexamethasone, thus highlighting the magnitude of the foregone incremental net benefit due to not adopting a more cost-effective clinical practice (83% Dexamethasone, 17% No Dexamethasone) earlier. The findings remain robust following variations in the model's parameters, with a 85% and 94% probability of faster recruitment being cost-effective given a cost-effectiveness threshold of £20,000 and £30,000 per Quality Adjusted Life Year respectively. Slow recruitment to randomised trials can have huge implications for healthcare systems as a result of not introducing a more cost-effective treatment earlier through faster patient recruitment.

Many countries now offer support to teenage mothers to help them to achieve long-term socioeconomic stability and to give a successful start to their children. The Family Nurse Partnership (FNP) is a licensed intensive home-visiting intervention developed in the USA and introduced into practice in England that involves up to 64 structured home visits from early pregnancy until the child's second birthday by specially recruited and trained family nurses. We aimed to assess the effectiveness of giving the programme to teenage first-time mothers on infant and maternal outcomes up to 24 months after birth. We did a pragmatic, non-blinded, randomised controlled, parallel-group trial in community midwifery settings at 18 partnerships between local authorities and primary and secondary care organisations in England. Eligible participants were nulliparous and aged 19 years or younger, and were recruited at less than 25 weeks' gestation. Field-based researchers randomly allocated mothers (1:1) via remote randomisation (telephone and web) to FNP plus usual care (publicly funded health and social care) or to usual care alone. Allocation was stratified by site and minimised by gestation (<16 weeks vs ≥16 weeks), smoking status (yes vs no), and preferred language of data collection (English vs non-English). Mothers and assessors (local researchers at baseline and 24 months' follow-up) were not masked to group allocation, but telephone interviewers were blinded. Primary endpoints were biomarker-calibrated self-reported tobacco use by the mother at late pregnancy, birthweight of the baby, the proportion of women with a second pregnancy within 24 months post-partum, and emergency attendances and hospital admissions for the child within 24 months post-partum. Analyses were by intention to treat. This trial is registered with ISRCTN, number ISRCTN23019866. Between June 16, 2009, and July 28, 2010, we screened 3251 women. After enrolment, 823 women were randomly assigned to receive FNP and 822 to usual care. All follow-up data were retrieved by April 25, 2014. 304 (56%) of 547 women assigned to FNP and 306 (56%) of 545 assigned to usual care smoked at late pregnancy (adjusted odds ratio [AOR] 0·90, 97·5% CI 0·64–1·28). Mean birthweight of 742 babies with mothers assigned to FNP was 3217·4 g (SD 618·0), whereas birthweight of 768 babies assigned to usual care was 3197·5 g (SD 581·5; adjusted mean difference 20·75 g, 97·5% CI −47·73 to 89·23. 587 (81%) of 725 assessed children with mothers assigned to FNP and 577 (77%) of 753 assessed children assigned to usual care attended an emergency department or were admitted to hospital at least once before their second birthday (AOR 1·32, 97·5% CI 0·99–1·76). 426 (66%) of 643 assessed women assigned to FNP and 427 (66%) 646 assigned to usual care had a second pregnancy within 2 years (AOR 1·01, 0·77–1·33). At least one serious adverse event (mainly clinical events associated with pregnancy and infancy period) was reported for 310 (38%) of 808 participants (mother–child) in the usual care group and 357 (44%) of 810 in the FNP group, none of which were considered related to the intervention. Adding FNP to the usually provided health and social care provided no additional short-term benefit to our primary outcomes. Programme continuation is not justified on the basis of available evidence, but could be reconsidered should supportive longer-term evidence emerge. Department of Health Policy Research Programme.

Background There is increasing interest in the capacity of adaptive designs to improve the efficiency of clinical trials. However, relatively little work has investigated how economic considerations – including the costs of the trial – might inform the design and conduct of adaptive clinical trials. Methods We apply a recently published Bayesian model of a value-based sequential clinical trial to data from the ‘Hydroxychloroquine Effectiveness in Reducing symptoms of hand Osteoarthritis’ (HERO) trial. Using parameters estimated from the trial data, including the cost of running the trial, and using multiple imputation to estimate the accumulating cost-effectiveness signal in the presence of missing data, we assess when the trial would have stopped had the value-based model been used. We used re-sampling methods to compare the design’s operating characteristics with those of a conventional fixed length design. Results In contrast to the findings of the only other published retrospective application of this model, the equivocal nature of the cost-effectiveness signal from the HERO trial means that the design would have stopped the trial close to, or at, its maximum planned sample size, with limited additional value delivered via savings in research expenditure. Conclusion Evidence from the two retrospective applications of this design suggests that, when the cost-effectiveness signal in a clinical trial is unambiguous, the Bayesian value-adaptive design can stop the trial before it reaches its maximum sample size, potentially saving research costs when compared with the alternative fixed sample size design. However, when the cost-effectiveness signal is equivocal, the design is expected to run to, or close to, the maximum sample size and deliver limited savings in research costs.

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).

IntroductionBiological disease-modifying antirheumatic drugs (bDMARDs) have revolutionised the treatment of inflammatory arthritis (IA). However, many people with IA still require planned orthopaedic surgery to reduce pain and improve function. Currently, bDMARDs are withheld during the perioperative period due to potential infection risk. However, this predisposes patients to IA flares and loss of disease control. The question of whether to stop or continue bDMARDs in the perioperative period has not been adequately addressed in a randomised controlled trial (RCT).Methods and analysisPERISCOPE is a multicentre, superiority, pragmatic RCT investigating the stoppage or continuation of bDMARDs. Participants will be assigned 1:1 to either stop or continue their bDMARDs during the perioperative period. We aim to recruit 394 adult participants with IA. Potential participants will be identified in secondary care hospitals in the UK, screened by a delegated clinician. If eligible and consenting, baseline data will be collected and randomisation completed. The primary outcome will be the self-reported PROMIS-29 (Patient Reported Outcome Measurement Information System) over the first 12 weeks postsurgery. Secondary outcome measures are as follows: PROMIS - Health Assessment Questionnaire (PROMIS-HAQ), EQ-5D-5L, Disease activity: generic global Numeric Rating Scale (patient and clinician), Self-Administered Patient Satisfaction scale, Health care resource use and costs, Medication use, Surgical site infection, delayed wound healing, Adverse events (including systemic infections) and disease-specific outcomes (according to IA diagnosis). The costs associated with stopping and continuing bDMARDs will be assessed. A qualitative study will explore the patients’ and clinicians’ acceptability and experience of continuation/stoppage of bDMARDs in the perioperative period and the impact postoperatively.Ethics and disseminationEthical approval for this study was received from the West of Scotland Research Ethics Committee on 25 April 2023 (REC Ref: 23/WS/0049). The findings from PERISCOPE will be submitted to peer-reviewed journals and feed directly into practice guidelines for the use of bDMARDs in the perioperative period.Trial registration numberISRCTN17691638.

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

Background Technology advances mean alternatives to hand-painted artificial eyes are possible, but the feasibility of conducting a large-scale trial is unknown. The aim was to assess the feasibility of collecting healthcare resource use and associated costs needed to undertake a large-scale randomised controlled trial (RCT) comparing the effectiveness and cost-effectiveness of hand-painted artificial eyes with digitally-printed artificial eyes. Methods Participants wore a digitally-printed artificial eye and a hand-painted artificial eye, for two weeks each, in a random order. Individual patient-level data was used to explore health outcomes (EQ-5D-5L) and resource use. Costs of the two artificial eye services were collected. A full economic evaluation was not conducted. An appropriate economic evaluation framework was developed to identify the relevant health economic data necessary for a future full trial. Results Thirty-five participants were randomised. Response rates were 97–100% for the EQ-5D-5L. Resource use questions were less well completed: 54% complete responses at baseline, 40% partial responses and 6% missing/invalid responses. The two follow-up points had similar rates. Eye services cost data were well completed. Mean utility was 0.77 after wearing the hand-painted eye and 0.83 after the digitally-printed eye. Average manufacturing times were 294 min (digitally-printed) and 355 min (hand-painted). Remake appointments were needed for digitally-printed eyes only. Estimated cost for the digitally-printed eye service is £404 and £347 for the hand-painted eye. Time between fitting and final evaluation was 56 days (digitally-printed eye) and 60 days (hand-painted). Results should be interpreted with caution, as estimates were based on a small sample. Conclusion It was possible to collect EQ-5D-5L, healthcare resource use and manufacturing times allowing a costing to be calculated. Thus, a large-scale RCT with full cost-effectiveness analysis would feasible. Refinements are suggested. Future economic analysis should consider how best to evaluate the service, possibility with modelling rather than within-trial analysis only. Trial registration ISRCTN85921622. Key messages regarding feasibility ‒ Lack of research in this area meant there were uncertainties in the ability to collect economic data. ‒ Standardised measures and clinician data were well completed; however, work is needed to refine resource use questionnaire. ‒ A full economic evaluation within a full-scale randomised controlled trial exploring the effectiveness of different artificial eyes is feasible.

IntroductionFalls and fall-related injuries are a serious cause of morbidity and cost to society. Environmental hazards are implicated as a major contributor to falls among older people. A recent Cochrane review found an environmental assessment, undertaken by an occupational therapist, to be an effective approach to reducing falls. However, none of the trials included a cost-effectiveness evaluation in the UK setting. This protocol describes a large multicentre trial investigating the clinical and cost-effectiveness of environmental assessment and modification within the home with the aim of preventing falls in older people.Methods and analysisA two-arm, modified cohort randomised controlled trial, conducted within England, with 1299 community-dwelling participants aged 65 years and above, who are at an increased risk of falls. Participants will be randomised 2:1 to receive either usual care or home assessment and modification. The primary outcome is rate of falls (falls/person/time) over 12 months assessed by monthly patient self-report falls calendars. Secondary self-reported outcome measures include: the proportion of single and multiple fallers, time to first fall over a 12-month period, quality of life (EuroQoL EQ-5D-5L) and health service utilisation at 4, 8 and 12 months. A nested qualitative study will examine the feasibility of providing the intervention and explore barriers, facilitators, workload implications and readiness to employ these interventions into routine practice. An economic evaluation will assess value for money in terms of cost per fall averted.Ethics and disseminationThis study protocol (including the original application and subsequent amendments) received a favourable ethical opinion from National Health Service West of Scotland REC 3. The trial results will be published in peer-reviewed journals and at conference presentations. A summary of the findings will be sent to participants.Trial registration number ISRCTN22202133; Pre-results.

Background Data from a feasibility study suggest that the use of an inelastic, short-stretch compression bandage following total knee arthroplasty is a safe technique that may improve patient-reported health outcomes, and that it is feasible to recruit to a full-scale study. Methods We will conduct a randomised controlled trial (RCT) of 2600 adult patients, which has 80% power to detect a 1 point difference in the Oxford Knee Score (a patient self-reported assessment of knee pain and function) at 52 weeks. Short stretch compression bandaging will be compared with standard wool and crepe bandaging following total knee arthroplasty. Recruitment will take place in orthopaedic units across the United Kingdom. Secondary outcomes include the EuroQol 5 Dimensions (EQ-5D)-5 L and EQ-5D-3 L scores, pain, length of hospital stay, and complications. Discussion The Knee Replacement Bandaging Study (KReBS) is a large study which aims to contribute to the evidence base for informing clinical decisions for the use of compression bandaging following knee arthroplasty. Trial registration International Standard Randomised Controlled Trial Register, ISRCTN 87127065 . Registered on 20 February 2017.

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.