UK robotic arthroplasty clinical and cost effectiveness randomised controlled trial for hips (RACER-Hip): a study protocol.

INTRODUCTION: The number of robotic-assisted hip replacement procedures has expanded globally with the intended aim of improving outcomes. Intraoperative robotic-arm systems add additional costs to total hip replacement (THR) surgery but may improve surgical precision and could contribute to diminished pain and improved function. Additionally, these systems may reduce the need for expensive revision surgery. Surgery with conventional instruments may be just as successful, quick and affordable. There is timely demand for a robust evaluation of this technology. METHODS AND ANALYSIS: The Robotic Arthroplasty Clinical and cost Effectiveness Randomised controlled trial for Hips (RACER-Hip) is a multicentre (minimum of six UK sites), participant-assessor blinded, randomised controlled trial. 378 participants with hip osteoarthritis requiring THR will be randomised (1:1) to receive robotic-assisted THR, or THR using conventional surgical instruments. The primary outcome is the Forgotten Joint Score at 12 months post-randomisation; a patient-reported outcome measure assessing participants' awareness of their joint when undertaking daily activities. Secondary outcomes will be collected post-operatively (pain, blood loss and opioid usage) and at 3, 6, 12, 24 months, then 5 and 10 years postrandomisation (including function, pain, health-related quality of life, reoperations and satisfaction). Allocation concealment will be accomplished using a computer-based randomisation procedure on the day of surgery. Blinding methods include the use of sham incisions for marker clusters and blinded operation notes. The primary analysis will adhere to the intention-to-treat principle. Results will adhere to Consolidated Standards of Reporting Trials statements. ETHICS AND DISSEMINATION: The trial was approved by an ethics committee (Solihull Research Ethics Committee, 30 June 2021, IRAS: 295831). Participants will provide informed consent before agreeing to participate. Results will be disseminated using peer-reviewed journal publications, presentations at international conferences and through the use of social media. We will develop plans to disseminate to patients and public with our patient partners. TRIAL REGISTRATION NUMBER: ISRCTN13374625.

A video-feedback parenting intervention to prevent enduring behaviour problems in at-risk children aged 12-36 months: the Healthy Start, Happy Start RCT.

BACKGROUND: Behaviour problems emerge early in childhood and place children at risk for later psychopathology. OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of a parenting intervention to prevent enduring behaviour problems in young children. DESIGN: A pragmatic, assessor-blinded, multisite, two-arm, parallel-group randomised controlled trial. SETTING: Health visiting services in six NHS trusts in England. PARTICIPANTS: A total of 300 at-risk children aged 12-36 months and their parents/caregivers. INTERVENTIONS: Families were allocated in a 1 : 1 ratio to six sessions of Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD) plus usual care or usual care alone. MAIN OUTCOME MEASURES: The primary outcome was the Preschool Parental Account of Children's Symptoms, which is a structured interview of behaviour symptoms. Secondary outcomes included caregiver-reported total problems on the Child Behaviour Checklist and the Strengths and Difficulties Questionnaire. The intervention effect was estimated using linear regression. Health and social care service use was recorded using the Child and Adolescent Service Use Schedule and cost-effectiveness was explored using the Preschool Parental Account of Children's Symptoms. RESULTS: In total, 300 families were randomised: 151 to VIPP-SD plus usual care and 149 to usual care alone. Follow-up data were available for 286 (VIPP-SD, n = 140; usual care, n = 146) participants and 282 (VIPP-SD, n = 140; usual care, n = 142) participants at 5 and 24 months, respectively. At the post-treatment (primary outcome) follow-up, a group difference of 2.03 on Preschool Parental Account of Children's Symptoms (95% confidence interval 0.06 to 4.01; p = 0.04) indicated a positive treatment effect on behaviour problems (Cohen's d = 0.20, 95% confidence interval 0.01 to 0.40). The effect was strongest for children's conduct [1.61, 95% confidence interval 0.44 to 2.78; p = 0.007 (d = 0.30, 95% confidence interval 0.08 to 0.51)] versus attention deficit hyperactivity disorder symptoms [0.29, 95% confidence interval -1.06 to 1.65; p = 0.67 (d = 0.05, 95% confidence interval -0.17 to 0.27)]. The Child Behaviour Checklist [3.24, 95% confidence interval -0.06 to 6.54; p = 0.05 (d = 0.15, 95% confidence interval 0.00 to 0.31)] and the Strengths and Difficulties Questionnaire [0.93, 95% confidence interval -0.03 to 1.9; p = 0.06 (d = 0.18, 95% confidence interval -0.01 to 0.36)] demonstrated similar positive treatment effects to those found for the Preschool Parental Account of Children's Symptoms. At 24 months, the group difference on the Preschool Parental Account of Children's Symptoms was 1.73 [95% confidence interval -0.24 to 3.71; p = 0.08 (d = 0.17, 95% confidence interval -0.02 to 0.37)]; the effect remained strongest for conduct [1.07, 95% confidence interval -0.06 to 2.20; p = 0.06 (d = 0.20, 95% confidence interval -0.01 to 0.42)] versus attention deficit hyperactivity disorder symptoms [0.62, 95% confidence interval -0.60 to 1.84; p = 0.32 (d = 0.10, 95% confidence interval -0.10 to 0.30)], with little evidence of an effect on the Child Behaviour Checklist and the Strengths and Difficulties Questionnaire. The primary economic analysis showed better outcomes in the VIPP-SD group at 24 months, but also higher costs than the usual-care group (adjusted mean difference £1450, 95% confidence interval £619 to £2281). No treatment- or trial-related adverse events were reported. The probability of VIPP-SD being cost-effective compared with usual care at the 24-month follow-up increased as willingness to pay for improvements on the Preschool Parental Account of Children's Symptoms increased, with VIPP-SD having the higher probability of being cost-effective at willingness-to-pay values above £800 per 1-point improvement on the Preschool Parental Account of Children's Symptoms. LIMITATIONS: The proportion of participants with graduate-level qualifications was higher than among the general public. CONCLUSIONS: VIPP-SD is effective in reducing behaviour problems in young children when delivered by health visiting teams. Most of the effect of VIPP-SD appears to be retained over 24 months. However, we can be less certain about its value for money. TRIAL REGISTRATION: Current Controlled Trials ISRCTN58327365. 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. 29. See the NIHR Journals Library website for further project information.

Behaviour problems in young children are common and are linked to mental and physical health problems, and educational and social difficulties. An important factor that influences the development of behaviour problems is the quality of care that children receive from their caregivers. This study aimed to test if a six-session parenting programme [called Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD)] reduced behaviour problems in children aged 1 or 2 years who were showing early signs of behaviour problems (e.g. restlessness, impulsivity, tantrums and aggression). VIPP-SD supports caregivers in responding to their child's communication and behaviour. A total of 300 families participated. All families continued to access usual health-care services (e.g. health visitors and general practitioners), but half of the families were randomly allocated to also receive the VIPP-SD programme. We visited all families when the study started, and at 5 and 24 months to see if the children whose families received VIPP-SD showed fewer behaviour problems. We measured the children's behaviour by completing interviews and questionnaires with their caregivers. We also analysed whether or not VIPP-SD was good value for money compared with existing services. We did this by comparing the cost of all of the standard health and community services that families accessed during their time in the study, taking account of the impact that VIPP-SD had on children's behaviour. The children in the VIPP-SD group had lower levels of behaviour problems following the programme than children whose parents did not receive the programme. On average, VIPP-SD children scored 2 points lower on the main measure of behaviour; an example difference would be tantrums being rated as mild rather than severe. By the 2-year visit, the VIPP-SD children continued to show lower levels of behaviour problems. It is less clear whether or not VIPP-SD is good value for money, as this depends on how much money policy-makers are willing to invest for reductions in behaviour problems. Overall, there is strong evidence that the VIPP-SD programme is effective in reducing behaviour problems in the short term. Most of this benefit appears to be maintained for the following 2 years. However, we are less certain about the long-term effect and the VIPP-SD's value for money.

Long-term Clinical and Cost-effectiveness of Early Endovenous Ablation in Venous Ulceration: A Randomized Clinical Trial.

Importance: One-year outcomes from the Early Venous Reflux Ablation (EVRA) randomized trial showed accelerated venous leg ulcer healing and greater ulcer-free time for participants who are treated with early endovenous ablation of lower extremity superficial reflux. Objective: To evaluate the clinical and cost-effectiveness of early endovenous ablation of superficial venous reflux in patients with venous leg ulceration. Design, Setting, and Participants: Between October 24, 2013, and September 27, 2016, the EVRA randomized clinical trial enrolled 450 participants (450 legs) with venous leg ulceration of less than 6 months' duration and superficial venous reflux. Initially, 6555 patients were assessed for eligibility, and 6105 were excluded for reasons including ulcer duration greater than 6 months, healed ulcer by the time of randomization, deep venous occlusive disease, and insufficient superficial venous reflux to warrant ablation therapy, among others. A total of 426 of 450 participants (94.7%) from the vascular surgery departments of 20 hospitals in the United Kingdom were included in the analysis for ulcer recurrence. Surgeons, participants, and follow-up assessors were not blinded to the treatment group. Data were analyzed from August 11 to November 4, 2019. Interventions: Patients were randomly assigned to receive compression therapy with early endovenous ablation within 2 weeks of randomization (early intervention, n = 224) or compression with deferred endovenous treatment of superficial venous reflux (deferred intervention, n = 226). Endovenous modality and strategy were left to the preference of the treating clinical team. Main Outcomes and Measures: The primary outcome for the extended phase was time to first ulcer recurrence. Secondary outcomes included ulcer recurrence rate and cost-effectiveness. Results: The early-intervention group consisted of 224 participants (mean [SD] age, 67.0 [15.5] years; 127 men [56.7%]; 206 White participants [92%]). The deferred-intervention group consisted of 226 participants (mean [SD] age, 68.9 [14.0] years; 120 men [53.1%]; 208 White participants [92%]). Of the 426 participants whose leg ulcer had healed, 121 (28.4%) experienced at least 1 recurrence during follow-up. There was no clear difference in time to first ulcer recurrence between the 2 groups (hazard ratio, 0.82; 95% CI, 0.57-1.17; P = .28). Ulcers recurred at a lower rate of 0.11 per person-year in the early-intervention group compared with 0.16 per person-year in the deferred-intervention group (incidence rate ratio, 0.658; 95% CI, 0.480-0.898; P = .003). Time to ulcer healing was shorter in the early-intervention group for primary ulcers (hazard ratio, 1.36; 95% CI, 1.12-1.64; P = .002). At 3 years, early intervention was 91.6% likely to be cost-effective at a willingness to pay of £20 000 ($26 283) per quality-adjusted life year and 90.8% likely at a threshold of £35 000 ($45 995) per quality-adjusted life year. Conclusions and Relevance: Early endovenous ablation of superficial venous reflux was highly likely to be cost-effective over a 3-year horizon compared with deferred intervention. Early intervention accelerated the healing of venous leg ulcers and reduced the overall incidence of ulcer recurrence. Trial Registration: ClinicalTrials.gov identifier: ISRCTN02335796.

Early versus deferred endovenous ablation of superficial venous reflux in patients with venous ulceration: the EVRA RCT.

BACKGROUND: Venous ulceration is a common and costly health-care issue worldwide, with poor healing rates greatly affecting patient quality of life. Compression bandaging has been shown to improve healing rates and reduce recurrence, but does not address the underlying cause, which is often superficial venous reflux. Surgical correction of the reflux reduces ulcer recurrence; however, the effect of early endovenous ablation of superficial venous reflux on ulcer healing is unclear. OBJECTIVES: To determine the clinical effectiveness and cost-effectiveness of compression therapy with early endovenous ablation of superficial venous reflux compared with compression therapy with deferred endovenous ablation in patients with venous ulceration. DESIGN: A pragmatic, two-arm, multicentre, parallel-group, open randomised controlled trial with a health economic evaluation. SETTING: Secondary care vascular centres in England. PARTICIPANTS: Patients aged ≥ 18 years with a venous leg ulcer of between 6 weeks' and 6 months' duration and an ankle-brachial pressure index of ≥ 0.8 who could tolerate compression and were deemed suitable for endovenous ablation of superficial venous reflux. INTERVENTIONS: Participants were randomised 1 : 1 to either early ablation (compression therapy and superficial endovenous ablation within 2 weeks of randomisation) or deferred ablation (compression therapy followed by endovenous ablation once the ulcer had healed). MAIN OUTCOME MEASURES: The primary outcome measure was time from randomisation to ulcer healing, confirmed by blinded assessment. Secondary outcomes included 24-week ulcer healing rates, ulcer-free time, clinical success (in addition to quality of life), costs and quality-adjusted life-years (QALYs). All analyses were performed on an intention-to-treat basis. RESULTS: A total of 450 participants were recruited (224 to early and 226 to deferred superficial endovenous ablation). Baseline characteristics were similar between the two groups. Time to ulcer healing was shorter in participants randomised to early superficial endovenous ablation than in those randomised to deferred ablation [hazard ratio 1.38, 95% confidence interval (CI) 1.13 to 1.68; p = 0.001]. Median time to ulcer healing was 56 (95% CI 49 to 66) days in the early ablation group and 82 (95% CI 69 to 92) days in the deferred ablation group. The ulcer healing rate at 24 weeks was 85.6% in the early ablation group, compared with 76.3% in the deferred ablation group. Median ulcer-free time was 306 [interquartile range (IQR) 240-328] days in the early ablation group and 278 (IQR 175-324) days in the deferred endovenous ablation group (p = 0.002). The most common complications of superficial endovenous ablation were pain and deep-vein thrombosis. Differences in repeated measures of Aberdeen Varicose Vein Questionnaire scores (p < 0.001), EuroQol-5 Dimensions index values (p = 0.03) and Short Form questionnaire-36 items body pain (p = 0.05) over the follow-up period were observed, in favour of early ablation. The mean difference in total costs between the early ablation and deferred ablation groups was £163 [standard error (SE) £318; p = 0.607]; however, there was a substantial and statistically significant gain in QALY over 1 year [mean difference between groups 0.041 (SE 0.017) QALYs; p = 0.017]. The incremental cost-effectiveness ratio of early ablation at 1 year was £3976 per QALY, with a high probability (89%) of being more cost-effective than deferred ablation at conventional UK decision-making thresholds (currently £20,000 per QALY). Sensitivity analyses using alternative statistical models give qualitatively similar results. LIMITATIONS: Only 7% of screened patients were recruited, treatment regimens varied significantly and technical success was assessed only in the early ablation group. CONCLUSIONS: Early endovenous ablation of superficial venous reflux, in addition to compression therapy and wound dressings, reduces the time to healing of venous leg ulcers, increases ulcer-free time and is highly likely to be cost-effective. FUTURE WORK: Longer-term follow-up is ongoing and will determine if early ablation will affect recurrence rates in the medium and long term. TRIAL REGISTRATION: Current Controlled Trials ISRCTN02335796. 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. 23, No. 24. See the NIHR Journals Library website for further project information.

Venous leg ulcers are open wounds occurring on the legs of patients with venous disease. They are common, painful and distressing and reduce patient quality of life. Leg ulcers often result from valves in the leg veins not working properly. The valves normally force blood back up towards the heart; however, blood can flow backwards (reflux) when valves do not work properly, and this can cause swelling and ulceration. Compression therapy (wrapping bandages around the legs) has been shown to help ulcers heal, but it does not treat the underlying reflux problem with the veins. Newer, less invasive, techniques (known as endovenous ablation) have taken over from surgery to correct venous reflux and are more acceptable to patients as they can be performed quickly under local anaesthetic. The aim of the trial was to find out if treating patients with leg ulcers by early endovenous ablation (within 2 weeks) and standard compression therapy can increase ulcer healing compared with standard compression therapy and delayed endovenous ablation once the ulcer has healed. In total, 450 people agreed to take part in this study and were treated in 20 hospitals across England. Participants were randomly allocated to either early or delayed endovenous ablation and followed up for 12 months. The trial found that treating the veins early resulted in quicker ulcer healing than delaying treatment until the ulcer had healed. The trial also showed that participants had more time without an ulcer if the treatment was performed early rather than after ulcer healing. No safety issues with early intervention were identified. There is some evidence that quality of life was better in the early treatment group and that people in this group had less body pain. Treating ulcers early appears likely to be more cost-effective (i.e. a better use of NHS resources) than delayed treatment. Future work will focus on collecting longer-term follow-up data to find out if early endovenous ablation also reduces the chances of the ulcer coming back.

A Randomized Trial of Early Endovenous Ablation in Venous Ulceration.

BACKGROUND: Venous disease is the most common cause of leg ulceration. Although compression therapy improves venous ulcer healing, it does not treat the underlying causes of venous hypertension. Treatment of superficial venous reflux has been shown to reduce the rate of ulcer recurrence, but the effect of early endovenous ablation of superficial venous reflux on ulcer healing remains unclear. METHODS: In a trial conducted at 20 centers in the United Kingdom, we randomly assigned 450 patients with venous leg ulcers to receive compression therapy and undergo early endovenous ablation of superficial venous reflux within 2 weeks after randomization (early-intervention group) or to receive compression therapy alone, with consideration of endovenous ablation deferred until after the ulcer was healed or until 6 months after randomization if the ulcer was unhealed (deferred-intervention group). The primary outcome was the time to ulcer healing. Secondary outcomes were the rate of ulcer healing at 24 weeks, the rate of ulcer recurrence, the length of time free from ulcers (ulcer-free time) during the first year after randomization, and patient-reported health-related quality of life. RESULTS: Patient and clinical characteristics at baseline were similar in the two treatment groups. The time to ulcer healing was shorter in the early-intervention group than in the deferred-intervention group; more patients had healed ulcers with early intervention (hazard ratio for ulcer healing, 1.38; 95% confidence interval [CI], 1.13 to 1.68; P=0.001). The median time to ulcer healing was 56 days (95% CI, 49 to 66) in the early-intervention group and 82 days (95% CI, 69 to 92) in the deferred-intervention group. The rate of ulcer healing at 24 weeks was 85.6% in the early-intervention group and 76.3% in the deferred-intervention group. The median ulcer-free time during the first year after trial enrollment was 306 days (interquartile range, 240 to 328) in the early-intervention group and 278 days (interquartile range, 175 to 324) in the deferred-intervention group (P=0.002). The most common procedural complications of endovenous ablation were pain and deep-vein thrombosis. CONCLUSIONS: Early endovenous ablation of superficial venous reflux resulted in faster healing of venous leg ulcers and more time free from ulcers than deferred endovenous ablation. (Funded by the National Institute for Health Research Health Technology Assessment Program; EVRA Current Controlled Trials number, ISRCTN02335796 .).

Preventing enduring behavioural problems in young children through early psychological intervention (Healthy Start, Happy Start): study protocol for a randomized controlled trial.

BACKGROUND: Behavioural problems are common in early childhood, and can result in enduring costs to the individual and society, including an increased risk of mental and physical illness, criminality, educational failure and drug and alcohol misuse. Most previous research has examined the impact of interventions targeting older children when difficulties are more established and harder to change, and have rarely included fathers. We are conducting a trial of a psychological intervention delivered to families with very young children, engaging both parents where possible. METHODS: This study is a two-arm, parallel group, researcher-blind, randomized controlled trial, to test the clinical effectiveness and cost-effectiveness of a parenting intervention, Video Feedback Intervention to Promote Positive Parenting and Sensitive Discipline (VIPP-SD) for parents of young children (12-36 months) at risk of behavioural difficulties. VIPP-SD is an evidence-based parenting intervention developed at Leiden University in the Netherlands which uses a video-feedback approach to support parents, particularly by enhancing parental sensitivity and sensitive discipline in caring for children. The trial will involve 300 families, who will be randomly allocated into either an intervention group, who will receive the video-feedback intervention (n = 150), or a control group, who will receive treatment as usual (n = 150). The trial will evaluate whether VIPP-SD, compared to treatment as usual, leads to lower levels of behavioural problems in young children who are at high risk of developing these difficulties. Assessments will be conducted at baseline, and 5 and 24 months post-randomization. The primary outcome measure is a modified version of the Preschool Parental Account of Child Symptoms (Pre-PACS), a structured clinical interview of behavioural symptoms. Secondary outcomes include caregiver-reported behavioural difficulties, parenting behaviours, parental sensitivity, parental mood and anxiety and parental relationship adjustment. An economic evaluation will also be carried out to assess the cost-effectiveness of the intervention compared to treatment as usual. DISCUSSION: If shown to be effective, the intervention could be delivered widely to parents and caregivers of young children at risk of behavioural problems as part of community based services. TRIAL REGISTRATION: ISRCTN Registry: ISRCTN58327365 . Registered 19 March 2015.

Protocol for a cohort study of adolescent mental health service users with a nested cluster randomised controlled trial to assess the clinical and cost-effectiveness of managed transition in improving transitions from child to adult mental health services (the MILESTONE study).

INTRODUCTION: Disruption of care during transition from child and adolescent mental health services (CAMHS) to adult mental health services may adversely affect the health and well-being of service users. The MILESTONE (Managing the Link and Strengthening Transition from Child to Adult Mental Healthcare) study evaluates the longitudinal course and outcomes of adolescents approaching the transition boundary (TB) of their CAMHS and determines the effectiveness of the model of managed transition in improving outcomes, compared with usual care. METHODS AND ANALYSIS: This is a cohort study with a nested cluster randomised controlled trial. Recruited CAMHS have been randomised to provide either (1) managed transition using the Transition Readiness and Appropriateness Measure score summary as a decision aid, or (2) usual care for young people reaching the TB. Participants are young people within 1 year of reaching the TB of their CAMHS in eight European countries; one parent/carer and a CAMHS clinician for each recruited young person; and adult mental health clinician or other community-based care provider, if young person transitions. The primary outcome is Health of the Nation Outcome Scale for Children and Adolescents (HoNOSCA) measuring health and social functioning at 15 months postintervention. The secondary outcomes include mental health, quality of life, transition experience and healthcare usage assessed at 9, 15 and 24 months postintervention. With a mean cluster size of 21, a total of 840 participants randomised in a 1:2 intervention to control are required, providing 89% power to detect a difference in HoNOSCA score of 0.30 SD. The addition of 210 recruits for the cohort study ensures sufficient power for studying predictors, resulting in 1050 participants and an approximate 1:3 randomisation. ETHICS AND DISSEMINATION: The study protocol was approved by the UK National Research Ethics Service (15/WM/0052) and equivalent ethics boards in participating countries. Results will be reported at conferences, in peer-reviewed publications and to all relevant stakeholder groups. TRIAL REGISTRATION NUMBER: ISRCTN83240263; NCT03013595 (pre-results).

Cost-effectiveness analysis of colorectal cancer screening with stool DNA testing in intermediate-incidence countries.

BACKGROUND: The aim of this study is to compare the cost-effectiveness of screening with stool DNA testing with that of screening with other tools (annual fecal occult blood testing, flexible sigmoidoscopy every 5 years, and colonoscopy every 10 years) or not screening at all. METHODS: We developed a Markov model to evaluate the above screening strategies in the general population 50 to 75 years of age in Taiwan. Sensitivity analyses were performed to assess the influence of various parameters on the cost-effectiveness of screening. A third-party payer perspective was adopted and the cost of dollar 13,000 per life-year saved (which is roughly the per capita GNP of Taiwan in 2003) was chosen as the ceiling ratio for assessing whether the program is cost-effective. RESULTS: Stool DNA testing every three, five, and ten years can reduce colorectal cancer mortality by 22%, 15%, and 9%, respectively. The associated incremental costs were dollar 9,794, dollar 9,335, and dollar 7,717, per life-year saved when compared with no screening. Stool DNA testing strategies were the least cost-effective with the cost per stool DNA test, referral rate with diagnostic colonoscopy, prevalence of large adenoma, and discount rate being the most influential parameters. CONCLUSION: In countries with a low or intermediate incidence of colorectal cancer, stool DNA testing is less cost-effective than the other currently recommended strategies for population-based screening, particularly targeting at asymptomatic subjects.