Clinical and cost-effectiveness of individualised (early) patient-directed rehabilitation versus standard rehabilitation after surgical repair of the rotator cuff of the shoulder: protocol for a multicentre, randomised controlled trial with integrated Quintet Recruitment Intervention (RaCeR 2).

INTRODUCTION: Despite the high number of operations and surgical advancement, rehabilitation after rotator cuff repair has not progressed for over 20 years. The traditional cautious approach might be contributing to suboptimal outcomes. Our aim is to assess whether individualised (early) patient-directed rehabilitation results in less shoulder pain and disability at 12 weeks after surgical repair of full-thickness tears of the rotator cuff compared with current standard (delayed) rehabilitation. METHODS AND ANALYSIS: The rehabilitation after rotator cuff repair (RaCeR 2) study is a pragmatic multicentre, open-label, randomised controlled trial with internal pilot phase. It has a parallel group design with 1:1 allocation ratio, full health economic evaluation and quintet recruitment intervention. Adults awaiting arthroscopic surgical repair of a full-thickness tear are eligible to participate. On completion of surgery, 638 participants will be randomised. The intervention (individualised early patient-directed rehabilitation) includes advice to the patient to remove their sling as soon as they feel able, gradually begin using their arm as they feel able and a specific exercise programme. Sling removal and movement is progressed by the patient over time according to agreed goals and within their own pain and tolerance. The comparator (standard rehabilitation) includes advice to the patient to wear the sling for at least 4 weeks and only to remove while eating, washing, dressing or performing specific exercises. Progression is according to specific timeframes rather than as the patient feels able. The primary outcome measure is the Shoulder Pain and Disability Index total score at 12-week postrandomisation. The trial timeline is 56 months in total, from September 2022. TRIAL REGISTRATION NUMBER: ISRCTN11499185.

Sertraline for anxiety in adults with a diagnosis of autism (STRATA): study protocol for a pragmatic, multicentre, double-blind, placebo-controlled randomised controlled trial.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to manage anxiety in adults with an autism diagnosis. However, their effectiveness and adverse effect profile in the autistic population are not well known. This trial aims to determine the effectiveness and cost-effectiveness of the SSRI sertraline in reducing symptoms of anxiety and improving quality of life in adults with a diagnosis of autism compared with placebo and to quantify any adverse effects. METHODS: STRATA is a two-parallel group, multi-centre, pragmatic, double-blind, randomised placebo-controlled trial with allocation at the level of the individual. It will be delivered through recruiting sites with autism services in 4 regional centres in the United Kingdom (UK) and 1 in Australia. Adults with an autism diagnosis and a Generalised Anxiety Disorder Assessment (GAD-7) score ≥ 10 at screening will be randomised 1:1 to either 25 mg sertraline or placebo, with subsequent flexible dose titration up to 200 mg. The primary outcome is GAD-7 scores at 16 weeks post-randomisation. Secondary outcomes include adverse effects, proportionate change in GAD-7 scores including 50% reduction, social anxiety, obsessive-compulsive symptoms, panic attacks, repetitive behaviours, meltdowns, depressive symptoms, composite depression and anxiety, functioning and disability and quality of life. Carer burden will be assessed in a linked carer sub-study. Outcome data will be collected using online/paper methods via video call, face-to-face or telephone according to participant preference at 16, 24 and 52 weeks post-randomisation, with brief safety checks and data collection at 1-2, 4, 8, 12 and 36 weeks. An economic evaluation to study the cost-effectiveness of sertraline vs placebo and a QuinteT Recruitment Intervention (QRI) to optimise recruitment and informed consent are embedded within the trial. Qualitative interviews at various times during the study will explore experiences of participating and taking the trial medication. DISCUSSION: Results from this study should help autistic adults and their clinicians make evidence-based decisions on the use of sertraline for managing anxiety in this population. TRIAL REGISTRATION: ISRCTN, ISRCTN15984604 . Registered on 08 February 2021. EudraCT 2019-004312-66. ANZCTR ACTRN12621000801819. Registered on 07 April 2021.

Autistic adults' views on the design and processes within randomised controlled trials: The APRiCoT study.

LAY ABSTRACT: Large randomised controlled trials are used to test healthcare treatments. Yet there are no large randomised controlled trials on effective treatments for common mental health issues affecting autistic adults. The purpose of this study was to learn what autistic adults think about randomised controlled trials in preparation for a randomised controlled trial testing a medication for anxiety. This means we wanted to know their opinions about the way randomised controlled trials are done, such as how people are chosen to be in the study and how the study is carried out. We did this by talking to 49 autistic adults individually and asking them questions. We found that most of the people we talked to were okay with the way randomised controlled trials are done. They thought it was fair and they liked that it was based on evidence. However, some autistic people might find it hard to take part in randomised controlled trials. Some people did not like the uncertainty of not knowing what treatment they would receive in a randomised controlled trial. Others felt too vulnerable and may have had bad experiences with healthcare in the past. We found that it is important to involve autistic people early on and at every stage when designing a clinical trial. Care about how clear and precise the study communication is will build trust and improve access to research. Our study indicates that it is possible to conduct large randomised controlled trials with and for autistic people. This can ultimately contribute to the improvement of healthcare outcomes for this population.

Lockdown Experiences and Views on Future Research Participation of Autistic Adults in the UK During the First 6 Months of the COVID-19 Pandemic.

Background: The COVID-19 pandemic resulted in large-scale public health restrictions and lockdowns across many countries. There is an increasing literature on the varied impact of such lockdowns in autistic adults. However, there is very little research on how the pandemic and related public health measures may impact the willingness of autistic people in engaging and taking part in research. The aim of this qualitative study was to explore autistic adults' experiences of the COVID-19 lockdown and how the pandemic may affect future research participation. Methods: We conducted in-depth interviews with 31 autistic adults between March and July 2020. Transcripts were analyzed thematically within a critical realism framework. Results: Participants identified positive aspects of lockdown such as enjoying the lack of social pressures and using their well-developed skills for dealing with uncertainty. Autistic people also shared challenges of adjusting to lockdown, for example, rapid change in daily routines. While hopeful about the freedom gained from easing restrictions, participants were concerned about the inconsistent communication and application of rules during the transition out of lockdown. This may have exacerbated already rising mental health issues among autistic people. The participants viewed research participation and engagement with increased relevance during the pandemic and welcomed efforts to conduct research using online methods of communication. Conclusion: The COVID-19 lockdown had a varied effect in the lives and routines of autistic people. However, health care providers and researchers need to be mindful of rising mental health issues in the aftermath of the pandemic, especially for people who were already vulnerable. The response to the pandemic may have offered opportunities for innovation in research processes enabling more autistic people to engage with research and making studies more inclusive.

Why is this an important issue?: We did not know how the pandemic and the strict restrictions that followed would affect autistic people's well-being and mental health.Also, there was a worry that the pandemic would affect the number of volunteers taking part in research that matters the most to autistic people. Thus, it was important to understand any implications for the way we conduct research with the autistic community after the pandemic. What was the purpose of this study?: We explored the experiences of autistic people living through the first 6 months of the COVID-19 lockdown in the United Kingdom. We were particularly interested in autistic people's views on how the pandemic may affect them taking part in research. What did the researchers do?: We co-produced this interview study to answer our research questions. We carried out in-depth interviews with 31 autistic people. We looked for patterns or themes in what the participants said. What were the results of the study?: Autistic people we interviewed reported being able to enjoy a quieter pace of life. They felt less anxious early in the lockdown. But they also faced great challenges adjusting to changes in their daily routines. Inconsistent public health communication caused worry during the transition out of lockdown. Unnecessary stress might have led to worsening of mental health issues in some people. Our participants held positive views on taking part in and engage with research, despite the pandemic. We identified opportunities that could make research more inclusive for autistic people, for example, online methods for taking consent and taking part in research remotely. What do these findings add to what was already known?: Our study adds to the evidence of the varied responses of autistic people to the pandemic and the public health measures that it led to. One important strength of our work is our focus on the impact of the pandemic on research and implications of future research. We learnt that autistic people welcome and value the use of online technology to reach study participants. Wider use of remote technology can make research more inclusive and participatory. What are potential weaknesses in the study?: Many of our participants were already had experience participating in research. Also most had relatively high education levels. We did not include autistic people with intellectual disabilities. We did not collect information on ethnicity. Our sample is likely to have little ethnic diversity. How will these findings help autistic adults now or in the future?: We describe the experiences of autistic people in the face of unprecedented circumstances. We found the need for clear public health communication to avoid unnecessary stress. The pandemic has provided the opportunity for a wider use of remote methods of research, even in areas where this was not done in the past (e.g., clinical trials). Our study found that such approaches would make research more inclusive.

CARE: Protocol of a randomised trial evaluating the feasibility of preoperative intentional weight loss to support postoperative recovery in patients with excess weight and colorectal cancer.

AIM: Excess weight increases the risk of morbidity following colorectal cancer surgery. Weight loss may improve morbidity, but it is uncertain whether patients can follow an intensive weight loss intervention while waiting for surgery and there are concerns about muscle mass loss. The aim of this trial is to assess the feasibility of intentional weight loss in this setting and determine progression to a definitive trial. METHODS: CARE is a prospectively registered, multicentre, feasibility, parallel, randomised controlled trial with embedded evaluation and optimisation of the recruitment process. Participants with excess weight awaiting curative colorectal resection for cancer are randomised 1:1 to care as usual or a low-energy nutritionally-replete total diet replacement programme with weekly remote behavioural support by a dietitian. Progression criteria will be based on the recruitment, engagement, adherence, and retention rates. Data will be collected on the 30-day postoperative morbidity, the typical primary outcome of prehabilitation trials. Secondary outcomes will include, among others, length of hospital stay, health-related quality of life, and body composition. Qualitative interviews will be used to understand patients' experiences of and attitudes towards trial participation and intervention engagement and adherence. CONCLUSION: CARE will evaluate the feasibility of intensive intentional weight loss as prehabilitation before colorectal cancer surgery. The results will determine the planning of a definitive trial.

Non-COVID-19 UK clinical trials and the COVID-19 pandemic: impact, challenges and possible solutions.

INTRODUCTION: The COVID-19 pandemic impacted the operationalisation of non-COVID-19 clinical trials globally, particularly site and participant recruitment and trial success/stoppage. Trials which anticipate recruitment challenges may embed methods such as the QuinteT Recruitment Intervention (QRI) to help identify and understand the sources of challenges. Such interventions can help shed light on pandemic-related challenges. This paper reports our experience of the impact of the COVID-19 pandemic on conducting clinical trials with an embedded QRI, highlighting how the QRI aided in identifying challenges and potential solutions, particularly related to the site set-up and participant recruitment. MAIN BODY: We report on 13 UK clinical trials which included a QRI. Information is from QRI data and researchers' experience and reflections. In most trials, recruitment was lower than even the lowest anticipated rates. The flexibility of the QRI facilitated rapid data collection to understand and document, and in some instances respond to, operational challenges. Challenges were mostly logistical, pandemic-related and beyond the control of the site or central trial teams. Specifically: disrupted and variable site opening timelines -often due to local research and development (R&D) delays- shortages of staff to recruit patients; fewer eligible patients or limited access to patients; and intervention-related factors. Almost all trials were affected by pandemic-related staffing issues including redeployment, prioritisation of COVID-19 care and research, and COVID-19-related staff illness and absence. Trials of elective procedures were particularly impacted by the pandemic, which caused changes to care/recruitment pathways, deprioritisation of services, reduced clinical and surgical capacity and longer waiting lists. Attempted solutions included extra engagement with staff and R&D departments, trial protocol changes (primarily moving online) and seeking additional resourcing. CONCLUSION: We have highlighted wide-ranging, extensive and consistent pandemic-related challenges faced by UK clinical trials, which the QRI helped to identify and, in some cases, address. Many challenges were insurmountable at individual trials or trials unit level. This overview highlights the need to streamline trial regulatory processes, address staffing crises, improve recognition of NHS research staff and for clearer, more nuanced central guidance on the prioritisation of studies and how to deal with the backlog. Pre-emptively embedding qualitative work and stakeholder consultation into trials with anticipated difficulties, moving some processes online, and flexible trial protocols may improve the resilience of trials in the current challenging context.

Informed consent in randomised controlled trials: further development and evaluation of the participatory and informed consent (PIC) measure.

BACKGROUND: Informed consent is an accepted ethical and legal prerequisite for trial participation, yet there is no standardised method of assessing patient understanding for informed consent. The participatory and informed consent (PIC) measure was developed for application to recruitment discussions to evaluate recruiter information provision and evidence of patient understanding. Preliminary evaluation of the PIC indicated the need to improve inter-rater and intra-rater reliability ratings and conduct further psychometric evaluation. This paper describes the assessment, revision and evaluation of the PIC within the context of OPTiMISE, a pragmatic primary care-based trial. METHODS: This study used multiple methods across two phases. In phase one, one researcher applied the existing PIC measure to 18 audio-recorded recruitment discussions from the OPTiMISE study and made detailed observational notes about any uncertainties in application. Appointments were sampled to be maximally diverse for patient gender, study centre, recruiter and before and after an intervention to optimise information provision. Application uncertainties were reviewed by the study team, revisions made and a coding manual developed and agreed. In phase two, the coding manual was used to develop tailored guidelines for applying the PIC to appointments within the OPTiMISE trial. Two researchers then assessed 27 further appointments, purposively sampled as above, to evaluate inter-rater and intra-rater reliability, content validity and feasibility. RESULTS: Application of the PIC to 18 audio-recorded OPTiMISE recruitment discussions resulted in harmonisation of the scales rating recruiter information provision and evidence of patient understanding, minor amendments to clarify wording and the development of detailed generic coding guidelines for applying the measure within any trial. Application of the revised measure using these guidelines to 27 further recruitment discussions showed good feasibility (time to complete), content validity (completion rate) and reliability (inter- and intra-rater) of the measure. CONCLUSION: The PIC provides a means to evaluate the content of information provided by recruiters, patient participation in recruitment discussions and, to some extent, evidence of patient understanding. Future work will use the measure to evaluate recruiter information provision and evidence of patient understanding both across and within trials.

Impact of video-assisted thoracoscopic lobectomy versus open lobectomy for lung cancer on recovery assessed using self-reported physical function: VIOLET RCT.

BACKGROUND: Lung cancer is the leading cause of cancer death. Surgery remains the main method of managing early-stage disease. Minimal-access video-assisted thoracoscopic surgery results in less tissue trauma than open surgery; however, it is not known if it improves patient outcomes. OBJECTIVE: To compare the clinical effectiveness and cost-effectiveness of video-assisted thoracoscopic surgery lobectomy with open surgery for the treatment of lung cancer. DESIGN, SETTING AND PARTICIPANTS: A multicentre, superiority, parallel-group, randomised controlled trial with blinding of participants (until hospital discharge) and outcome assessors conducted in nine NHS hospitals. Adults referred for lung resection for known or suspected lung cancer, with disease suitable for both surgeries, were eligible. Participants were followed up for 1 year. INTERVENTIONS: Participants were randomised 1 : 1 to video-assisted thoracoscopic surgery lobectomy or open surgery. Video-assisted thoracoscopic surgery used one to four keyhole incisions without rib spreading. Open surgery used a single incision with rib spreading, with or without rib resection. MAIN OUTCOME MEASURES: The primary outcome was self-reported physical function (using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30) at 5 weeks. Secondary outcomes included upstaging to pathologic node stage 2 disease, time from surgery to hospital discharge, pain in the first 2 days, prolonged pain requiring analgesia at > 5 weeks, adverse health events, uptake of adjuvant treatment, overall and disease-free survival, quality of life (Quality of Life Questionnaire Core 30, Quality of Life Questionnaire Lung Cancer 13 and EQ-5D) at 2 and 5 weeks and 3, 6 and 12 months, and cost-effectiveness. RESULTS: A total of 503 patients were randomised between July 2015 and February 2019 (video-assisted thoracoscopic surgery, n = 247; open surgery, n = 256). One participant withdrew before surgery. The mean age of patients was 69 years; 249 (49.5%) patients were men and 242 (48.1%) did not have a confirmed diagnosis. Lobectomy was performed in 453 of 502 (90.2%) participants and complete resection was achieved in 429 of 439 (97.7%) participants. Quality of Life Questionnaire Core 30 physical function was better in the video-assisted thoracoscopic surgery group than in the open-surgery group at 5 weeks (video-assisted thoracoscopic surgery, n = 247; open surgery, n = 255; mean difference 4.65, 95% confidence interval 1.69 to 7.61; p = 0.0089). Upstaging from clinical node stage 0 to pathologic node stage 1 and from clinical node stage 0 or 1 to pathologic node stage 2 was similar (p ≥ 0.50). Pain scores were similar on day 1, but lower in the video-assisted thoracoscopic surgery group on day 2 (mean difference -0.54, 95% confidence interval -0.99 to -0.09; p = 0.018). Analgesic consumption was 10% lower (95% CI -20% to 1%) and the median hospital stay was less (4 vs. 5 days, hazard ratio 1.34, 95% confidence interval 1.09, 1.65; p = 0.006) in the video-assisted thoracoscopic surgery group than in the open-surgery group. Prolonged pain was also less (relative risk 0.82, 95% confidence interval 0.72 to 0.94; p = 0.003). Time to uptake of adjuvant treatment, overall survival and progression-free survival were similar (p ≥ 0.28). Fewer participants in the video-assisted thoracoscopic surgery group than in the open-surgery group experienced complications before and after discharge from hospital (relative risk 0.74, 95% confidence interval 0.66 to 0.84; p < 0.001 and relative risk 0.81, 95% confidence interval 0.66 to 1.00; p = 0.053, respectively). Quality of life to 1 year was better across several domains in the video-assisted thoracoscopic surgery group than in the open-surgery group. The probability that video-assisted thoracoscopic surgery is cost-effective at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year is 1. LIMITATIONS: Ethnic minorities were under-represented compared with the UK population (< 5%), but the cohort reflected the lung cancer population. CONCLUSIONS: Video-assisted thoracoscopic surgery lobectomy was associated with less pain, fewer complications and better quality of life without any compromise to oncologic outcome. Use of video-assisted thoracoscopic surgery is highly likely to be cost-effective for the NHS. FUTURE WORK: Evaluation of the efficacy of video-assisted thoracoscopic surgery with robotic assistance, which is being offered in many hospitals. TRIAL REGISTRATION: This trial is registered as ISRCTN13472721. FUNDING: This project was funded by the National Institute for Health and Care Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 48. See the NIHR Journals Library website for further project information.

BACKGROUND: Lung cancer is a common cause of cancer death worldwide. If the disease is caught early, the part of the lung containing the tumour can be removed in an operation called a lobectomy. The operation can be carried out through a large cut so that the surgeon has a full view of the lung, which is called open surgery, or using several small cuts and a camera, which is called video-assisted thoracoscopic (keyhole) surgery. It is thought that, as keyhole surgery is less invasive, patients recover quicker. However, to the best of our knowledge, there are no high-quality research studies that are applicable to UK practice to support this. This study was conducted so that it could be determined, based on high-quality evidence, which operation provides the best treatment and recovery for patients. WHO PARTICIPATED?: Five hundred and three adults referred for lobectomy for known or suspected lung cancer from nine hospitals in the UK. WHAT WAS INVOLVED?: Participants were randomly allocated to either receive keyhole or open surgery. Participants were followed up for 12 months. We collected information on further treatment, hospital visits, safety information and disease progression over this period. Participants were also asked to complete questionnaires about their health and recovery. WHAT DID THE TRIAL FIND?: For patients with early-stage lung cancer who underwent a lobectomy, keyhole surgery led to less pain, less time in hospital and better quality of life than open surgery, without having a detrimental effect on cancer progression or survival. Keyhole surgery was found to be cost-effective and to provide excellent value for money for the NHS.

Rehabilitation following rotator cuff repair: A survey exploring clinical equipoise among surgical members of the British Elbow and Shoulder Society.

Background: We investigated clinical equipoise across surgical members of the British Elbow and Shoulder Society (BESS) in relation to rehabilitation following rotator cuff repair. Method: An online survey explored clinical equipoise regarding early patient-directed versus standard rehabilitation after rotator cuff repair to inform the design of a national randomised controlled trial (RCT). It described different clinical scenarios relating to patient age, tear size, location and whether other patient-related and intra-operative factors would influence equipoise. Results: 76 surgeons completed the survey. 81% agreed/ strongly agreed that early mobilisation might benefit recovery; 57% were neutral/ disagreed that this approach risks re-tear. 87% agreed/ strongly agreed that there is clinical uncertainty about the effectiveness of different approaches to rehabilitation. As age of the patient and tear size increased, the proportion of respondents who would agree to recruit and accept the outcome of randomisation reduced, and this was compounded if subscapularis was torn. Other factors that influenced equipoise were diabetes and non-secure repair. Conclusion: Surgical members of BESS recognise uncertainty about the effectiveness of different approaches to rehabilitation following rotator cuff repair. We identified a range of factors that influence clinical equipoise that will be considered in the design of a new RCT.

Variations in policies for accessing elective musculoskeletal procedures in the English National Health Service: A documentary analysis.

OBJECTIVE: The overall aim of this study was to investigate how commissioning policies for accessing clinical procedures compare in the context of the English National Health Service. Our primary objective was to compare policy wording and categorise any variations identified. Our secondary objective was to explore how any points of variation relate to national guidance. METHODS: This study entailed documentary analysis of commissioning policies that stipulated criteria for accessing eight elective musculoskeletal procedures. For each procedure, we retrieved policies held by regions with higher and lower rates of clinical activity relative to the national average. Policies were subjected to content and thematic analysis, using constant comparison techniques. Matrices and descriptive reports were used to compare themes across policies for each procedure and derive categories of variation that arose across two or more procedures. National guidance relating to each procedure were identified and scrutinised, to explore whether these provided context for explaining the policy variations. RESULTS: Thirty-five policy documents held by 14 geographic regions were included in the analysis. Policies either focused on a single procedure/treatment or covered several procedures/treatments in an all-encompassing document. All policies stipulated criteria that needed to be fulfilled prior to accessing treatment, but there were inconsistences in the evidence cited. Policies varied in recurring ways, with respect to specification of non-surgical treatments and management, requirements around time spent using non-surgical approaches, diagnostic requirements, requirements around symptom severity and disease progression, and use of language, in the form of terms and phrases ('threshold modifiers') which could open up or restrict access to care. National guidance was identified for seven of the procedures, but this guidance did not specify criteria for accessing the procedures in question, making direct comparisons with regional policies difficult. CONCLUSIONS: This, to our knowledge, is the first study to identify recurring ways in which policies for accessing treatment can vary within a single-payer system with universal coverage. The findings raise questions around whether formulation of commissioning policies should receive more central support to promote greater consistency - especially where evidence is uncertain, variable or lacking.

Arthroscopic hip surgery compared with personalised hip therapy in people over 16 years old with femoroacetabular impingement syndrome: UK FASHIoN RCT.

BACKGROUND: Femoroacetabular impingement syndrome is an important cause of hip pain in young adults. It can be treated by arthroscopic hip surgery or with physiotherapist-led conservative care. OBJECTIVE: To compare the clinical effectiveness and cost-effectiveness of hip arthroscopy with best conservative care. DESIGN: The UK FASHIoN (full trial of arthroscopic surgery for hip impingement compared with non-operative care) trial was a pragmatic, multicentre, randomised controlled trial that was carried out at 23 NHS hospitals. PARTICIPANTS: Participants were included if they had femoroacetabular impingement, were aged ≥ 16 years old, had hip pain with radiographic features of cam or pincer morphology (but no osteoarthritis) and were believed to be likely to benefit from hip arthroscopy. INTERVENTION: Participants were randomly allocated (1 : 1) to receive hip arthroscopy followed by postoperative physiotherapy, or personalised hip therapy (i.e. an individualised physiotherapist-led programme of conservative care). Randomisation was stratified by impingement type and recruiting centre using a central telephone randomisation service. Outcome assessment and analysis were masked. MAIN OUTCOME MEASURE: The primary outcome was hip-related quality of life, measured by the patient-reported International Hip Outcome Tool (iHOT-33) 12 months after randomisation, and analysed by intention to treat. RESULTS: Between July 2012 and July 2016, 648 eligible patients were identified and 348 participants were recruited. In total, 171 participants were allocated to receive hip arthroscopy and 177 participants were allocated to receive personalised hip therapy. Three further patients were excluded from the trial after randomisation because they did not meet the eligibility criteria. Follow-up at the primary outcome assessment was 92% (N = 319; hip arthroscopy, n = 157; personalised hip therapy, n = 162). At 12 months, mean International Hip Outcome Tool (iHOT-33) score had improved from 39.2 (standard deviation 20.9) points to 58.8 (standard deviation 27.2) points for participants in the hip arthroscopy group, and from 35.6 (standard deviation 18.2) points to 49.7 (standard deviation 25.5) points for participants in personalised hip therapy group. In the primary analysis, the mean difference in International Hip Outcome Tool scores, adjusted for impingement type, sex, baseline International Hip Outcome Tool score and centre, was 6.8 (95% confidence interval 1.7 to 12.0) points in favour of hip arthroscopy (p = 0.0093). This estimate of treatment effect exceeded the minimum clinically important difference (6.1 points). Five (83%) of six serious adverse events in the hip arthroscopy group were related to treatment and one serious adverse event in the personalised hip therapy group was not. Thirty-eight (24%) personalised hip therapy patients chose to have hip arthroscopy between 1 and 3 years after randomisation. Nineteen (12%) hip arthroscopy patients had a revision arthroscopy. Eleven (7%) personalised hip therapy patients and three (2%) hip arthroscopy patients had a hip replacement within 3 years. LIMITATIONS: Study participants and treating clinicians were not blinded to the intervention arm. Delays were encountered in participants accessing treatment, particularly surgery. Follow-up lasted for 3 years. CONCLUSION: Hip arthroscopy and personalised hip therapy both improved hip-related quality of life for patients with femoroacetabular impingement syndrome. Hip arthroscopy led to a greater improvement in quality of life than personalised hip therapy, and this difference was clinically significant at 12 months. This study does not demonstrate cost-effectiveness of hip arthroscopy compared with personalised hip therapy within the first 12 months. Further follow-up will reveal whether or not the clinical benefits of hip arthroscopy are maintained and whether or not it is cost-effective in the long term. TRIAL REGISTRATION: Current Controlled Trials ISRCTN64081839. 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. 26, No. 16. See the NIHR Journals Library website for further project information.

In some people, the ball and the socket of the hip joint develop so that they do not fit together properly. This is called hip impingement, and is an important cause of hip and groin pain in young and middle-aged adults. Treatments include physiotherapy and surgery. Physiotherapy typically involves a programme of 6­10 outpatient consultations that aim to strengthen the muscles around the hip: we called this personalised hip therapy. Surgery can be carried out by a keyhole operation, called a hip arthroscopy, which aims to reshape the hip to prevent impingement. Surgery is normally followed by some physiotherapy. We performed a research study to compare the results of hip arthroscopy and personalised hip therapy in people with hip impingement. A total of 348 people with painful hip impingement in 23 hospitals in the UK agreed to take part. About half were treated with hip arthroscopy and half with personalised hip therapy. We used questionnaires to ask participants about pain in the hip and their ability to do everyday things at 6 months and 1 year after entering the study. At 2 and 3 years, we asked if patients required any additional treatments. We found that both groups improved, but those treated with hip arthroscopy improved a moderate amount more than those treated with personalised hip therapy. However, these improvements were not cost-effective compared with personalised hip therapy at 1 year. We need to see whether or not this difference continues after several years, but the results, so far, suggest that if a person has painful hip impingement, then hip arthroscopy offers greater improvements than personalised hip therapy.

Video-Assisted Thoracoscopic or Open Lobectomy in Early-Stage Lung Cancer.

Video-Assisted Thoracoscopic Surgery or Open Lobectomy in Early-Stage Lung CancerIn a patient with early-stage lung cancer, is resection by video-assisted thoracoscopic surgery (VATS) versus open resection superior with respect to the postoperative recovery? This question was addressed in a multicenter randomized trial in more than 500 patients. At 5 weeks after surgery, the physical function mean score was 73 in the VATS group and 67 in the open surgery group (function scores range from 0 to 100, with higher scores indicating better function). Of the participants allocated to VATS, 30.7% had serious adverse events after discharge compared with 37.8% of those allocated to open surgery. At 52 weeks, there were no differences in cancer progression-free survival.

Barriers to recruitment to an orthopaedic randomized controlled trial comparing two surgical procedures for ankle arthritis : a qualitative study.

AIMS: A multicentre, randomized, clinician-led, pragmatic, parallel-group orthopaedic trial of two surgical procedures was set up to obtain high-quality evidence of effectiveness. However, the trial faced recruitment challenges and struggled to maintain recruitment rates over 30%, although this is not unusual for surgical trials. We conducted a qualitative study with the aim of gathering information about recruitment practices to identify barriers to patient consent and participation to an orthopaedic trial. METHODS: We collected 11 audio recordings of recruitment appointments and interviews of research team members (principal investigators and research nurses) from five hospitals involved in recruitment to an orthopaedic trial. We analyzed the qualitative data sets thematically with the aim of identifying aspects of informed consent and information provision that was either unclear, disrupted, or hindered trial recruitment. RESULTS: Recruiters faced four common obstacles when recruiting to a surgical orthopaedic trial: patient preferences for an intervention; a complex recruitment pathway; various logistical issues; and conflicting views on equipoise. Clinicians expressed concerns that the trial may not show significant differences in the treatments, validating their equipoise. However, they experienced role conflicts due to their own preference and perceived patient preference for an intervention arm. CONCLUSION: This study provided initial information about barriers to recruitment to an orthopaedic randomized controlled trial. We shared these findings in an all-site investigators' meeting and encouraged researchers to find solutions to identified barriers; this led to the successful completion of recruitment. Complex trials may benefit for using of a mixed-methods approach to mitigate against recruitment failure, and to improve patient participation and informed consent. Cite this article: Bone Jt Open 2021;2(8):631-637.

What empirical research has been undertaken on the ethics of clinical research in India? A systematic scoping review and narrative synthesis.

INTRODUCTION: The post-2005 rise in clinical trials and clinical research conducted in India was accompanied by frequent reports of unethical practices, leading to a series of regulatory changes. We conducted a systematic scoping review to obtain an overview of empirical research pertaining to the ethics of clinical trials/research in India. METHODS: Our search strategy combined terms related to ethics/bioethics, informed consent, clinical trials/research and India, across nine databases, up to November 2019. Peer-reviewed research exploring ethical aspects of clinical trials/research in India with any stakeholder groups was included. We developed an evidence map, undertook a narrative synthesis and identified research gaps. A consultation exercise with stakeholders in India helped contextualise the review and identify additional research priorities. RESULTS: Titles/Abstracts of 9699 articles were screened, full text of 282 obtained and 80 were included. Research on the ethics of clinical trials/research covered a wide range of topics, often conducted with little to no funding. Studies predominantly examined what lay (patients/public) and professional participants (eg, healthcare staff/students/faculty) know about topics such as research ethics or understand from the information given to obtain their consent for research participation. Easily accessible groups, namely ethics committee members and healthcare students were frequently researched. Research gaps included developing a better understanding of the recruitment-informed consent process, including the doctor-patient interaction, in multiple contexts and exploring issues of equity and justice in clinical trials/research. CONCLUSION: The review demonstrates that while a wide range of topics have been studied in India, the focus is largely on assessing knowledge levels across different population groups. This is a useful starting point, but fundamental questions remain unanswered about informed consent processes and broader issues of inequity that pervade the clinical trials/research landscape. A priority-setting exercise and appropriate funding mechanisms to support researchers in India would help improve the clinical trials/research ecosystem.

A Feasibility and Acceptability Trial of Social Cognitive Therapy in Early Psychosis Delivered Through a Virtual World: The VEEP Study.

BACKGROUND: Addressing specific social cognitive difficulties is an important target in early psychosis and may help address poor functional outcomes. However, structured interventions using standard therapy settings including groups suffer from difficulties in recruitment and retention. AIMS: To address these issues, we aimed to modify an existing group social cognitive intervention entitled 'Social Cognition and Interaction Training' (SCIT) to be delivered through a virtual world environment (Second Life ©). METHODS: A single arm nonrandomized proof-of-concept trial of SCIT-VR was conducted. Five groups of three to five individuals per group were recruited over 6 months. Eight sessions of SCIT-VR therapy were delivered through the virtual world platform Second Life© over a 5-week intervention window. Feasibility was examined using recruitment rates and retention. Acceptability was examined using qualitative methods. Secondary outcomes including social cognitive indices, functioning, and anxiety were measured pre- and postintervention. RESULTS: The SCIT-VR therapy delivered was feasible (36% consent rate and 73.3% intervention completion rate), acceptable (high overall postsession satisfaction scores) and safe (no serious adverse events), and had high levels of participant satisfaction. Users found the environment immersive. Prepost changes were found in emotion recognition scores and levels of anxiety. There were no signs of clinical deterioration on any of the secondary measures. CONCLUSION: This proof-of-concept pilot trial suggested that delivering SCIT-VR through a virtual world is feasible and acceptable. There were some changes in prepost outcome measures that suggest the intervention has face validity. There is sufficient evidence to support a larger powered randomized controlled trial. CLINICAL TRIAL REGISTRATION: ISRCTN, identifier 41443166.

Co-designing a virtual world with young people to deliver social cognition therapy in early psychosis.

AIMS: Co-design implies genuine partnership in the generation of knowledge between service users and researchers. Service user involvement in research has been encouraged in government policy, but it is rarely achieved, especially at trial initial stages. Co-designed with service users, we adapted existing manualised social cognition intervention for people with a first episode of psychosis to a virtual world environment. METHODS: We invited a group of young people who have used mental health services to co-design a virtual environment to deliver an accessible social cognition intervention to a hard to engage service user group. We used an iterative process with young service users and the design team that included developing initial ideas, creating a prototype and testing the virtual world. RESULTS: Twenty young service users of local mental healthcare services provided feedback on the design and delivery of the intervention. Reflecting the demographic of the sample, young people felt the virtual environment should be familiar, urban spaces, akin to therapy rooms or classrooms they have used in real-life situations rather than non-traditional therapy spaces that were initially proposed. CONCLUSION: The co-design process led to the development of a specific design, approach and protocol to be tested in a proof-of-concept trial. Young service users were integral to an agile and iterative design. Technological innovations should be routinely co-designed and co-produced if they are to realise their potential to deliver acceptable and affordable mental health interventions.

Maintenance antipsychotic treatment versus discontinuation strategies following remission from first episode psychosis: systematic review.

BACKGROUND: Understanding the relative risks of maintenance treatment versus discontinuation of antipsychotics following remission in first episode psychosis (FEP) is an important area of practice. METHOD: A systematic review and meta-analysis. Prospective experimental studies including a parallel control group were identified to compare maintenance antipsychotic treatment with total discontinuation or medication discontinuation strategies following remission in FEP. RESULTS: Seven studies were included. Relapse rates were higher in the discontinuation group (53%; 95% CIs: 39%, 68%; N = 290) compared with maintenance treatment group (19%; 95% CIs: 0.05%, 37%; N = 230). In subgroup analyses, risk difference of relapse was lower in studies with a longer follow-up period, a targeted discontinuation strategy, a higher relapse threshold, a larger sample size, and samples with patients excluded for drug or alcohol dependency. Insufficient studies included psychosocial functioning outcomes for a meta-analysis. CONCLUSIONS: There is a higher risk of relapse for those who undergo total or targeted discontinuation strategies compared with maintenance antipsychotics in FEP samples. The effect size is moderate and the risk difference is lower in trials of targeted discontinuation strategies. DECLARATION OF INTEREST: A.T. has received honoraria and support from Janssen-Cilag and Otsuka Pharmaceuticals for meetings and has been has been an investigator on unrestricted investigator-initiated trials funded by AstraZeneca and Janssen-Cilag. He has also previously held a Pfizer Neurosciences Research Grant. S.M. has received sponsorship from Otsuka and Lundbeck to attend an academic congress and owns shares in GlaxoSmithKline and AstraZeneca. J.H. has attended meetings supported by Sunovion Pharmaceuticals.

Hip arthroscopy versus best conservative care for the treatment of femoroacetabular impingement syndrome (UK FASHIoN): a multicentre randomised controlled trial.

BACKGROUND: Femoroacetabular impingement syndrome is an important cause of hip pain in young adults. It can be treated by arthroscopic hip surgery, including reshaping the hip, or with physiotherapist-led conservative care. We aimed to compare the clinical effectiveness of hip arthroscopy with best conservative care. METHODS: UK FASHIoN is a pragmatic, multicentre, assessor-blinded randomised controlled trial, done at 23 National Health Service hospitals in the UK. We enrolled patients with femoroacetabular impingement syndrome who presented at these hospitals. Eligible patients were at least 16 years old, had hip pain with radiographic features of cam or pincer morphology but no osteoarthritis, and were believed to be likely to benefit from hip arthroscopy. Patients with bilateral femoroacetabular impingement syndrome were eligible; only the most symptomatic hip was randomly assigned to treatment and followed-up. Participants were randomly allocated (1:1) to receive hip arthroscopy or personalised hip therapy (an individualised, supervised, and progressive physiotherapist-led programme of conservative care). Randomisation was stratified by impingement type and recruiting centre and was done by research staff at each hospital, using a central telephone randomisation service. Patients and treating clinicians were not masked to treatment allocation, but researchers who collected the outcome assessments and analysed the results were masked. The primary outcome was hip-related quality of life, as measured by the patient-reported International Hip Outcome Tool (iHOT-33) 12 months after randomisation, and analysed in all eligible participants who were allocated to treatment (the intention-to-treat population). This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN64081839, and is closed to recruitment. FINDINGS: Between July 20, 2012, and July 15, 2016, we identified 648 eligible patients and recruited 348 participants: 171 participants were allocated to receive hip arthroscopy and 177 to receive personalised hip therapy. Three further patients were excluded from the trial after randomisation because they did not meet the eligibility criteria. Follow-up at the primary outcome assessment was 92% (319 of 348 participants). At 12 months after randomisation, mean iHOT-33 scores had improved from 39·2 (SD 20·9) to 58·8 (27·2) for participants in the hip arthroscopy group, and from 35·6 (18·2) to 49·7 (25·5) in the personalised hip therapy group. In the primary analysis, the mean difference in iHOT-33 scores, adjusted for impingement type, sex, baseline iHOT-33 score, and centre, was 6·8 (95% CI 1·7-12·0) in favour of hip arthroscopy (p=0·0093). This estimate of treatment effect exceeded the minimum clinically important difference (6·1 points). There were 147 patient-reported adverse events (in 100 [72%] of 138 patients) in the hip arthroscopy group) versus 102 events (in 88 [60%] of 146 patients) in the personalised hip therapy group, with muscle soreness being the most common of these (58 [42%] vs 69 [47%]). There were seven serious adverse events reported by participating hospitals. Five (83%) of six serious adverse events in the hip arthroscopy group were related to treatment, and the one in the personalised hip therapy group was not. There were no treatment-related deaths, but one patient in the hip arthroscopy group developed a hip joint infection after surgery. INTERPRETATION: Hip arthroscopy and personalised hip therapy both improved hip-related quality of life for patients with femoroacetabular impingement syndrome. Hip arthroscopy led to a greater improvement than did personalised hip therapy, and this difference was clinically significant. Further follow-up will reveal whether the clinical benefits of hip arthroscopy are maintained and whether it is cost effective in the long term. FUNDING: The Health Technology Assessment Programme of the National Institute of Health Research.

Personalised Hip Therapy: development of a non-operative protocol to treat femoroacetabular impingement syndrome in the FASHIoN randomised controlled trial.

INTRODUCTION: Femoroacetabular impingement (FAI) syndrome is increasingly recognised as a cause of hip pain. As part of the design of a randomised controlled trial (RCT) of arthroscopic surgery for FAI syndrome, we developed a protocol for non-operative care and evaluated its feasibility. METHODS: In phase one, we developed a protocol for non-operative care for FAI in the UK National Health Service (NHS), through a process of systematic review and consensus gathering. In phase two, the protocol was tested in an internal pilot RCT for protocol adherence and adverse events. RESULTS: The final protocol, called Personalised Hip Therapy (PHT), consists of four core components led by physiotherapists: detailed patient assessment, education and advice, help with pain relief and an exercise-based programme that is individualised, supervised and progressed over time. PHT is delivered over 12-26 weeks in 6-10 physiotherapist-patient contacts, supplemented by a home exercise programme. In the pilot RCT, 42 patients were recruited and 21 randomised to PHT. Review of treatment case report forms, completed by physiotherapists, showed that 13 patients (62%) received treatment that had closely followed the PHT protocol. 13 patients reported some muscle soreness at 6 weeks, but there were no serious adverse events. CONCLUSION: PHT provides a structure for the non-operative care of FAI and offers guidance to clinicians and researchers in an evolving area with limited evidence. PHT was deliverable within the National Health Service, is safe, and now forms the comparator to arthroscopic surgery in the UK FASHIoN trial (ISRCTN64081839). TRIAL REGISTRATION NUMBER: ISRCTN 09754699.

How outcome prediction could affect patient decision making in knee replacements: a qualitative study.

BACKGROUND: There is approximately a 17 % dissatisfaction rate with knee replacements. Calls for tools that can pre-operatively identify patients at risk of being dissatisfied have been widespread. However, it is not known how to present such information to patients, how it would affect their decision making process, and at what part of the pathway such a tool should be used. METHODS: Using focus groups involving 12 participants and in-depth interviews with 10 participants, we examined how individual predictions of outcome could affect patients' decision making by providing fictitious predictions to patients at different stages of treatment. A thematic analysis was used to analyse the data. RESULTS: Our results demonstrate several interesting findings. Firstly, patients who have received information from friends and family are unwilling to adjust their expectation of outcome down (i.e. to a worse outcome), but highly willing to adjust it up (to a better outcome). This is an example of the optimism bias, and suggests that the effect on expectation of a poor outcome prediction would be blunted. Secondly, patients generally wanted a "bottom line" outcome, rather than lots of detail. Thirdly, patients who were earlier in their treatment for osteoarthritis were more likely to find the information useful, and it was more likely to affect their decision, than patients later in their treatment pathway. CONCLUSION: This research suggest that an outcome prediction tool would have most effect targeted towards people at the start of their treatment pathway, with a "bottom line" prediction of outcome. However, any effect on expectation and decision making of a poor outcome prediction is likely to be blunted by the optimism bias. These findings merit replication in a larger sample size.