The OdonAssist inflatable device for assisted vaginal birth-the ASSIST II study (United Kingdom).

BACKGROUND: Decreasing rates of assisted vaginal birth have been paralleled with increasing rates of cesarean deliveries over the last 40 years. The OdonAssist is a novel device for assisted vaginal birth. Iterative changes to clinical parameters, device design, and technique have been made to improve device efficacy and usability. OBJECTIVE: This study aimed to determine if the feasibility, safety, and efficacy of the OdonAssist device were sufficient to justify conducting a future randomized controlled trial. STUDY DESIGN: An open-label nonrandomized study of 104 participants having a clinically indicated assisted vaginal birth using the OdonAssist was undertaken at Southmead Hospital, Bristol, United Kingdom. Data were also collected from participants who consented to participate in the study but for whom trained OdonAssist operators were not available, providing a nested cohort. The primary clinical outcome was the proportion of births successfully expedited with the OdonAssist. Secondary outcomes included clinical, patient-reported, operator-reported, device and health care utilization. Neonatal outcome data were reviewed at day 28, and maternal outcomes were investigated up to day 90. Given that the number of successful OdonAssist births was ≥61 out of 104, the hypothesis of a poor rate of 50% was rejected in favor of a good rate of ≥65%. RESULTS: Between August 2019 and June 2021, 941 (64%) of the 1471 approached, eligible participants consented to participate. Of these, 104 received the OdonAssist intervention. Birth was assisted in all cephalic vertex fetal positions, at all stations ≥1 cm below the ischial spines (with or without regional analgesia). The OdonAssist was effective in 69 of the 104 (66%) cases, consistent with the hypothesis of a good efficacy rate. There were no serious device-related maternal or neonatal adverse reactions, and there were no serious adverse device effects. Only 4% of neonatal soft tissue bruising in the successful OdonAssist group was considered device-related, as opposed to 20% and 23% in the unsuccessful OdonAssist group and the nested cohort, respectively. Participants reported high birth perception scores. All practitioners found the device use to be straightforward. CONCLUSION: Recruitment to an interventional study of a new device for assisted vaginal birth is feasible; 64% of eligible participants were willing to participate. The success rate of the OdonAssist was comparable to that of the Kiwi OmniCup when introduced in the same unit in 2002, meeting the threshold for a randomized controlled trial to compare the OdonAssist with current standard practice. There were no disadvantages of study participation in terms of maternal and neonatal outcomes. There were potential advantages of using the OdonAssist, particularly reduced neonatal soft tissue injury. The same application technique is used for all fetal positions, with all operators deeming the device straightforward to use. This study provides important data to inform future study design.

Functional and quality of life outcomes of localised prostate cancer treatments (Prostate Testing for Cancer and Treatment [ProtecT] study).

OBJECTIVE: To investigate the functional and quality of life (QoL) outcomes of treatments for localised prostate cancer and inform treatment decision-making. PATIENTS AND METHODS: Men aged 50-69 years diagnosed with localised prostate cancer by prostate-specific antigen testing and biopsies at nine UK centres in the Prostate Testing for Cancer and Treatment (ProtecT) trial were randomised to, or chose one of, three treatments. Of 2565 participants, 1135 men received active monitoring (AM), 750 a radical prostatectomy (RP), 603 external-beam radiotherapy (EBRT) with concurrent androgen-deprivation therapy (ADT) and 77 low-dose-rate brachytherapy (BT, not a randomised treatment). Patient-reported outcome measures (PROMs) completed annually for 6 years were analysed by initial treatment and censored for subsequent treatments. Mixed effects models were adjusted for baseline characteristics using propensity scores. RESULTS: Treatment-received analyses revealed different impacts of treatments over 6 years. Men remaining on AM experienced gradual declines in sexual and urinary function with age (e.g., increases in erectile dysfunction from 35% of men at baseline to 53% at 6 years and nocturia similarly from 20% to 38%). Radical treatment impacts were immediate and continued over 6 years. After RP, 95% of men reported erectile dysfunction persisting for 85% at 6 years, and after EBRT this was reported by 69% and 74%, respectively (P < 0.001 compared with AM). After RP, 36% of men reported urinary leakage requiring at least 1 pad/day, persisting for 20% at 6 years, compared with no change in men receiving EBRT or AM (P < 0.001). Worse bowel function and bother (e.g., bloody stools 6% at 6 years and faecal incontinence 10%) was experienced by men after EBRT than after RP or AM (P < 0.001) with lesser effects after BT. No treatment affected mental or physical QoL. CONCLUSION: Treatment decision-making for localised prostate cancer can be informed by these 6-year functional and QoL outcomes.

Conveying Equipoise during Recruitment for Clinical Trials: Qualitative Synthesis of Clinicians' Practices across Six Randomised Controlled Trials.

BACKGROUND: Randomised controlled trials (RCTs) are essential for evidence-based medicine and increasingly rely on front-line clinicians to recruit eligible patients. Clinicians' difficulties with negotiating equipoise is assumed to undermine recruitment, although these issues have not yet been empirically investigated in the context of observable events. We aimed to investigate how clinicians conveyed equipoise during RCT recruitment appointments across six RCTs, with a view to (i) identifying practices that supported or hindered equipoise communication and (ii) exploring how clinicians' reported intentions compared with their actual practices. METHODS AND FINDINGS: Six pragmatic UK-based RCTs were purposefully selected to include several clinical specialties (e.g., oncology, surgery) and types of treatment comparison. The RCTs were all based in secondary-care hospitals (n = 16) around the UK. Clinicians recruiting to the RCTs were interviewed (n = 23) to understand their individual sense of equipoise about the RCT treatments and their intentions for communicating equipoise to patients. Appointments in which these clinicians presented the RCT to trial-eligible patients were audio-recorded (n = 105). The appointments were analysed using thematic and content analysis approaches to identify practices that supported or challenged equipoise communication. A sample of appointments was independently coded by three researchers to optimise reliability in reported findings. Clinicians and patients provided full written consent to be interviewed and have appointments audio-recorded. Interviews revealed that clinicians' sense of equipoise varied: although all were uncertain about which trial treatment was optimal, they expressed different levels of uncertainty, ranging from complete ambivalence to clear beliefs that one treatment was superior. Irrespective of their personal views, all clinicians intended to set their personal biases aside to convey trial treatments neutrally to patients (in accordance with existing evidence). However, equipoise was omitted or compromised in 48/105 (46%) of the recorded appointments. Three commonly recurring practices compromised equipoise communication across the RCTs, irrespective of clinical context. First, equipoise was overridden by clinicians offering treatment recommendations when patients appeared unsure how to proceed or when they asked for the clinician's expert advice. Second, clinicians contradicted equipoise by presenting imbalanced descriptions of trial treatments that conflicted with scientific information stated in the RCT protocols. Third, equipoise was undermined by clinicians disclosing their personal opinions or predictions about trial outcomes, based on their intuition and experience. These broad practices were particularly demonstrated by clinicians who had indicated in interviews that they held less balanced views about trial treatments. A limitation of the study was that clinicians volunteering to take part in the research might have had a particular interest in improving their communication skills. However, the frequency of occurrence of equipoise issues across the RCTs suggests that the findings are likely to be reflective of clinical recruiters' practices more widely. CONCLUSIONS: Communicating equipoise is a challenging process that is easily disrupted. Clinicians' personal views about trial treatments encroached on their ability to convey equipoise to patients. Clinicians should be encouraged to reflect on personal biases and be mindful of the common ways in which these can arise in their discussions with patients. Common pitfalls that recurred irrespective of RCT context indicate opportunities for specific training in communication skills that would be broadly applicable to a wide clinical audience.

Role of information in preparing men for transrectal ultrasound guided prostate biopsy: a qualitative study embedded in the ProtecT trial.

BACKGROUND: The histological diagnosis of prostate cancer requires a prostate needle biopsy. Little is known about the relationship between information provided to prepare men for transrectal ultrasound guided biopsy (TRUS-Bx) and how men experience biopsy. The objectives were a) to understand men's experiences of biopsy as compared to their expectations; and b) to propose current evidence-based information for men undergoing TRUS-Bx. METHODS: Between February 2006 and May 2008, 1,147 men undergoing a standardised 10-core transrectal ultrasound guided biopsy protocol under antibiotic cover following a PSA 3.0-19.9 ng/ml in the Prostate Testing for Cancer and Treatment (ProtecT) trial, completed questionnaires about biopsy symptoms. In this embedded qualitative study, in-depth interviews were undertaken with 85 men (mean age 63.6 yrs, mean PSA 4.5 ng/ml) to explore men's experiences of prostate biopsy and how the experience might be improved. Interview data were analysed thematically using qualitative research methods. Findings from the qualitative study were used to guide selection of key findings from the questionnaire study in developing a patient information leaflet preparing men for biopsy. RESULTS: Although most men tolerated TRUS-Bx, a quarter reported problematic side-effects and anxiety. Side effects were perceived as problematic and anxiety arose most commonly when experiences deviated from information provided. Men who were unprepared for elements of TRUS-Bx procedure or its sequelae responded by contacting health professionals for reassurance and voiced frustration that pre-biopsy information had understated the possible severity or duration of pain/discomfort and bleeding. Findings from questionnaire and interview data were combined to propose a comprehensive, evidence-based patient information leaflet for TRUS-Bx. CONCLUSIONS: Men reported anxiety associated with TRUS-Bx or its side-effects most commonly if they felt inadequately prepared for the procedure. Data from this qualitative study and the previous questionnaire study have been used to propose an updated, comprehensive evidence-based set of information for men undergoing TRUS-Bx.

The association of time between diagnosis and major resection with poorer colorectal cancer survival: a retrospective cohort study.

BACKGROUND: Colorectal cancer survival in the UK is lower than in other developed countries, but the association of time interval between diagnosis and treatment on excess mortality remains unclear. METHODS: Using data from cancer registries in England, we identified 46,511 patients with localised colorectal cancer between 1996-2009, who were 15 years and older, and who underwent a major surgical resection within 62 days of diagnosis. We used relative survival and excess risk modeling to investigate the association of time between diagnosis and major resection (exposure) with survival (outcome). RESULTS: Compared to patients who had major resection within 25-38 days of diagnosis, patients with a shorter time interval between diagnosis and resection and those waiting longer for resection had higher excess mortality (Excess Hazards Ratio, EHR <25 vs 25-38 days: 1.50; 95% Confidence Interval, CI: 1.37 to 1.66; EHR 39-62 vs 25-38 days : 1.16; 95% CI: 1.04 to 1.29). Excess mortality was associated with age (EHR 75+ vs. 15-44 year olds: 2.62; 95% CI: 2.00 to 3.42) and deprivation (EHR most vs. least deprived: 1.27; 95% CI: 1.12 to 1.45), but time between diagnosis and resection did not explain these differences. CONCLUSION: Within 62 days of diagnosis, a U-shaped association of time between diagnosis and major resection with excess mortality for localised colorectal cancer was evident. This indicates a complicated treatment pathway, particularly for patients who had resection earlier than 25 days, and requires further investigation.

The importance of dietary change for men diagnosed with and at risk of prostate cancer: a multi-centre interview study with men, their partners and health professionals.

BACKGROUND: The diagnosis of prostate cancer (PC) can provide a trigger for dietary change, and there is evidence that healthier diets may improve quality of life and clinical outcomes. However, men's views about dietary change in PC survivorship are largely unknown. This multi-centre qualitative interview study explored men's views about dietary change in PC survivorship, to better understand motivations for, and barriers to, achieving desired changes. The role of radical and active surveillance treatments on dietary change and the influence of men's partners were examined. Focus groups also evaluated stakeholder opinion, including healthcare professionals, about the provision of dietary advice to PC patients. METHODS: A multi-centre interview study explored views about diet and motivations for, and barriers to, dietary change in men at elevated risk or diagnosed with PC following prostate specific antigen (PSA) testing. 58 men and 11 partners were interviewed. Interviews and focus groups were undertaken with 11 healthcare professionals, 5 patients and 4 partners to evaluate stakeholders' opinions about the feasibility and acceptability of providing dietary advice to PC patients. Data were analysed using methods of constant comparison and thematic analysis. RESULTS: Over half of diagnosed men reported making dietary changes, primarily to promote general or prostate health or facilitate coping, despite their uncertainty about diet-PC links. Interest in dietary advice was high. Information needs varied depending on treatment received, with men on active surveillance more frequently modifying their diet and regarding this as an adjunct therapy. Men considered their partners integral to implementing changes. Provision of dietary advice to men diagnosed with PC was considered by healthcare professionals and men to be feasible and appropriate in the context of a holistic 'care package'. CONCLUSIONS: Many men make positive dietary changes after PC diagnosis, which are perceived by men and their partners to bring psychological and general health benefits and could help future dietary intervention trials. Men and their partners desire more and better dietary information that may support PC survivorship, particularly among those embarking on active surveillance/monitoring programmes. There are opportunities for healthcare professionals to support PC patients both clinically and psychologically by the routine integration of healthy eating advice into survivorship care plans.

Exploring the experiences and perceptions of patients awaiting rotator cuff repair surgery: An integrated qualitative study within the POWER pilot and feasibility trial.

BACKGROUND: As waiting times for orthopaedic surgery increase, there have been calls to move from 'waiting lists' to 'preparation lists', to better prepare patients for surgery. In this context, a pilot randomised controlled trial (POWER) was conducted, comparing physiotherapist-led exercise to waiting-list control (usual care), for patients awaiting rotator cuff repair surgery. This qualitative study was integrated within the pilot trial. OBJECTIVES: Explore the experiences of adults awaiting rotator cuff repair surgery in the NHS. Explore the acceptability of the physiotherapist-led exercise intervention. Explore the barriers and enablers to recruitment, retention, and adherence. DESIGN: Integrated qualitative study with semi-structured telephone interviews. METHODS: Adults awaiting rotator cuff repair, consenting to participate in the trial were eligible. Sampling was purposive regarding age, gender, randomised allocation, and hospital site. Interviews were audio-recorded and transcribed. Data were analysed using Reflexive Thematic Analysis. RESULTS: 20 participants were recruited (age range 49-81 years; 12 male, 10 randomised to physiotherapist-led exercise). Many participants were unable to recall their experiences of trial processes; nonetheless, three themes were identified from the data: experience of shoulder pain and pathway to treatment; communication and decision-making in the context of rotator cuff repair surgery; and experiences of the POWER physiotherapist-led exercise intervention and processes. CONCLUSIONS: Patients experience significant burden due to shoulder pain. Their journey to surgery can be long, confusing, and associated with perceived abandonment. In a future trial, the intervention should offer opportunity for shared decision-making, optional exit from the surgical pathway, and an individualised exercise programme.

Addressing barriers and identifying facilitators to support informed consent and recruitment in the Cavernous malformations A Randomised Effectiveness (CARE) pilot phase trial: insights from the integrated QuinteT recruitment intervention (QRI).

Background: It was anticipated that recruitment to the Cavernous malformations: A Randomised Effectiveness (CARE) pilot randomised trial would be challenging. The trial compared medical management and surgery (neurosurgical resection or stereotactic radiosurgery) with medical management alone, for people with symptomatic cerebral cavernous malformation (ISRCTN41647111). Previous trials comparing surgical and medical management for intracranial vascular malformations failed to recruit to target. A QuinteT Recruitment Intervention was integrated during trial accrual, September 2021-April 2023 inclusive, to improve informed consent and recruitment. Methods: The QuinteT Recruitment Intervention combined iterative collection and analysis of quantitative data (28 trial site screening logs recording numbers/proportions screened, eligible, approached and randomised) and qualitative data (79 audio-recorded recruitment discussions, 19 interviews with healthcare professionals, 11 interviews with patients, 2 investigator workshops, and observations of study meetings, all subject to thematic, content or conversation analysis). We triangulated quantitative and qualitative data to identify barriers and facilitators to recruitment and how and why these arose. Working with the chief investigators and trial management group, we addressed barriers and facilitators with corresponding actions to improve informed consent and recruitment. Findings: Barriers identified included how usual care practices made equipoise challenging, multi-disciplinary teams sometimes overrode recruiter equipoise and logistical issues rendered symptomatic cavernoma diagnosis and assessment for stereotactic radiosurgery challenging. Facilitators identified included the preparedness of some neurosurgeons' to offer surgery to people otherwise offered medical management alone, multi-disciplinary team equipoise, and effective information provision presenting participation as a solution to equipoise regarding management. Actions, before and during recruitment, to improve inclusivity of site screening, approach and effectiveness of information provision resulted in 72 participants recruited following a 5-month extension, exceeding the target of 60 participants. Interpretation: QuinteT Recruitment Intervention insights revealed barriers and facilitators, enabling identification of remedial actions. Recruitment to a definitive trial would benefit from further training/support to encourage clinicians to be comfortable approaching patients to whom medical management is usually offered, and broadening the pool of neurosurgeons and multi-disciplinary team members prepared to offer surgery, particularly stereotactic radiosurgery. Funding: National Institute for Health and Care Research.

Time from diagnosis to surgery and prostate cancer survival: a retrospective cohort study.

BACKGROUND: A diagnosis of prostate cancer leads to emotional distress and anxiety, prompting calls for rapid diagnostic pathways. Nevertheless, it remains unclear what impact time between diagnosis and surgery has upon prostate cancer survival. METHODS: Using national databases for England (cancer registries, Hospital Episode Statistics and Office of National Statistics), we identified 17,043 men with prostate cancer, aged 15 years and older, diagnosed in 1996-2009, and who had surgical resection with curative intent within 6 months of diagnosis. We used relative survival to investigate associations between waiting times and five- and ten-year survival. RESULTS: Five- and ten-year relative survival estimates for the total study sample were 1.04 (95% CI: 1.04 to 1.05) and 1.08 (95% CI: 1.06-1.09), respectively. There were no notable differences in survival between patients who had surgery at 0-3 and 4-6 months after diagnosis. Relative survival was higher among the elderly (>65) and those with well and moderately differentiated tumours. CONCLUSION: The high relative survival in our cohort probably reflects adherence to selection criteria for surgery among men with localised prostate cancer. Among men treated with surgery within 6 months of diagnosis, we found little evidence of an association between time from diagnosis to surgery and survival.

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.

Women's and midwives' views on the optimum process for informed consent for research in a feasibility study involving an intrapartum intervention: a qualitative study.

BACKGROUND: Recruitment to intrapartum research is complex. Women are expected to understand unfamiliar terminology and assess potential harm versus benefit to their baby and themselves, often when an urgent intervention is required. Time pressures of intrapartum interventions are a major challenge for recruitment discussions taking place during labour, with research midwives expected to present, discuss and answer questions whilst maintaining equipoise. However, little is known about these interactions. An integrated qualitative study (IQS) was used to investigate information provision for women invited to participate in the Assist II feasibility study investigating the OdonAssist™-a novel device for use in assisted vaginal birth with an aim to generate a framework of good practice for information provision. METHODS: Transcripts of in-depth interviews with women participants (n = 25), with recruiting midwives (n = 6) and recruitment discussions between midwives and women (n = 21), accepting or declining participation, were coded and interpreted using thematic analysis and content analysis to investigate what was helpful to women and what could be improved. RESULTS: Recruiting women to intrapartum research is complicated by factors that impact on women's understanding and decision-making. Three key themes were derived from the data: (i) a woman-centred recruitment process, (ii) optimising the recruitment discussion and (iii) making a decision for two. CONCLUSION: Despite evidence from the literature that women would like information provision and the research discussion to take place in the antenatal period, intrapartum studies still vary in the recruitment processes they offer women. Particularly concerning is that some women are given information for the first time whilst in labour, when they are known to feel particularly vulnerable, and contextual factors may influence decision-making; therefore, we propose a framework for good practice for information provision for research involving interventions initiated in the intrapartum period as a woman centred, and acceptable model of recruitment, which addresses the concerns of women and midwives and facilitates fair inclusion into intrapartum trials. TRIAL REGISTRATION: ISRCTN. This qualitative research was undertaken as part of the ASSIST II Trial (trial registration number: ISRCTN38829082. Prospectively registered on 26/06/2019).

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.

Qualitative data sharing practices in clinical trials in the UK and Ireland: towards the production of good practice guidance.

Background: Data sharing enables researchers to conduct novel research with previously collected datasets, thus maximising scientific findings and cost effectiveness, and reducing research waste. The value of sharing, even de-identified, quantitative data from clinical trials is well recognised with a moderated access approach recommended. While substantial challenges to sharing quantitative data remain, there are additional challenges for sharing qualitative data in trials. Incorporating the necessary information about how qualitative data will be shared into already complex trial recruitment and consent processes proves challenging. The aim of this study was to explore whether and how trial teams share qualitative data collected as part of the design, conduct, analysis, or delivery of clinical trials. Methods: Phase 1 involved semi-structured, in-depth qualitative interviews and focus groups with key trial stakeholder groups including trial managers and clinical trialists (n=3), qualitative researchers in trials (n=9), members of research funding bodies (n=2) and trial participants (n=1). Data were analysed using thematic analysis. In Phase 2, we conducted a content analysis of 16 participant information leaflets (PIL) and consent forms (CF) for trials that collected qualitative data. Results: Three key themes were identified from our Phase 1 findings: ' Understanding and experiences of the potential benefits of sharing qualitative data from trials', 'Concerns about qualitative data sharing', and ' Future guidance and funding'. In phase 2, the PILs and CFs received revealed that the benefits of data sharing for participants were only explained in two of the study documents. Conclusions: The value of sharing qualitative data was acknowledged, but there are many uncertainties as to how, when, and where to share this data. In addition, there were ethical concerns in relation to the consent process required for qualitative data sharing in trials. This study provides insight into the existing practice of qualitative data sharing in trials.

Duroplasty for injured cervical spinal cord with uncontrolled swelling: protocol of the DISCUS randomized controlled trial.

BACKGROUND: Cervical traumatic spinal cord injury is a devastating condition. Current management (bony decompression) may be inadequate as after acute severe TSCI, the swollen spinal cord may become compressed against the surrounding tough membrane, the dura. DISCUS will test the hypothesis that, after acute, severe traumatic cervical spinal cord injury, the addition of dural decompression to bony decompression improves muscle strength in the limbs at 6 months, compared with bony decompression alone. METHODS: This is a prospective, phase III, multicenter, randomized controlled superiority trial. We aim to recruit 222 adults with acute, severe, traumatic cervical spinal cord injury with an American Spinal Injury Association Impairment Scale grade A, B, or C who will be randomized 1:1 to undergo bony decompression alone or bony decompression with duroplasty. Patients and outcome assessors are blinded to study arm. The primary outcome is change in the motor score at 6 months vs. admission; secondary outcomes assess function (grasp, walking, urinary + anal sphincters), quality of life, complications, need for further surgery, and mortality, at 6 months and 12 months from randomization. A subgroup of at least 50 patients (25/arm) also has observational monitoring from the injury site using a pressure probe (intraspinal pressure, spinal cord perfusion pressure) and/or microdialysis catheter (cord metabolism: tissue glucose, lactate, pyruvate, lactate to pyruvate ratio, glutamate, glycerol; cord inflammation: tissue chemokines/cytokines). Patients are recruited from the UK and internationally, with UK recruitment supported by an integrated QuinteT recruitment intervention to optimize recruitment and informed consent processes. Estimated study duration is 72 months (6 months set-up, 48 months recruitment, 12 months to complete follow-up, 6 months data analysis and reporting results). DISCUSSION: We anticipate that the addition of duroplasty to standard of care will improve muscle strength; this has benefits for patients and carers, as well as substantial gains for health services and society including economic implications. If the addition of duroplasty to standard treatment is beneficial, it is anticipated that duroplasty will become standard of care. TRIAL REGISTRATION: IRAS: 292031 (England, Wales, Northern Ireland) - Registration date: 24 May 2021, 296518 (Scotland), ISRCTN: 25573423 (Registration date: 2 June 2021); ClinicalTrials.gov number : NCT04936620 (Registration date: 21 June 2021); NIHR CRN 48627 (Registration date: 24 May 2021).

Physiotherapist-led exercise versus usual care (waiting-list) control for patients awaiting rotator cuff repair surgery: A pilot randomised controlled trial (POWER).

BACKGROUND: Once a decision to undergo rotator cuff repair surgery is made, patients are placed on the waiting list. It can take weeks or months to receive surgery. There has been a call to move from waiting lists to 'preparation' lists to better prepare patients for surgery and to ensure it remains an appropriate treatment option for them. OBJECTIVE: To evaluate the feasibility, as measured by recruitment rates, treatment fidelity and follow-up rates, of a future multi-centre randomised controlled trial to compare the clinical and cost-effectiveness of undertaking a physiotherapist-led exercise programme while waiting for surgery versus usual care (waiting-list control). DESIGN: Two-arm, multi-centre pilot randomised controlled trial with feasibility objectives in six NHS hospitals in England. METHOD: Adults (n = 76) awaiting rotator cuff repair surgery were recruited and randomly allocated to a programme of physiotherapist-led exercise (n = 38) or usual care control (n = 38). RESULTS: Of 302 eligible patients, 76 (25%) were randomised. Of 38 participants randomised to physiotherapist-led exercise, 28 (74%) received the exercise programme as intended. 51/76 (67%) Shoulder Pain and Disability Index questionnaires were returned at 6-months. Of 76 participants, 32 had not received surgery after 6-months (42%). Of those 32, 20 were allocated to physiotherapist-led exercise; 12 to usual care control. CONCLUSIONS: A future multi-centre randomised controlled trial is feasible but would require planning for variable recruitment rates between sites, measures to improve treatment fidelity and opportunity for surgical exit, and optimisation of follow-up. A fully powered, randomised controlled trial is now needed to robustly inform clinical decision-making.

Complex and alternate consent pathways in clinical trials: methodological and ethical challenges encountered by underserved groups and a call to action.

BACKGROUND: Informed consent is considered a fundamental requirement for participation in trials, yet obtaining consent is challenging in a number of populations and settings. This may be due to participants having communication or other disabilities, their capacity to consent fluctuates or they lack capacity, or in emergency situations where their medical condition or the urgent nature of the treatment precludes seeking consent from either the participant or a representative. These challenges, and the subsequent complexity of designing and conducting trials where alternative consent pathways are required, contribute to these populations being underserved in research. Recognising and addressing these challenges is essential to support trials involving these populations and ensure that they have an equitable opportunity to participate in, and benefit from, research. Given the complex nature of these challenges, which are encountered by both adults and children, a cross-disciplinary approach is required. DISCUSSION: A UK-wide collaboration, a sub-group of the Trial Conduct Working Group in the MRC-NIHR Trial Methodology Research Partnership, was formed to collectively address these challenges. Members are drawn from disciplines including bioethics, qualitative research, trials methodology, healthcare professions, and social sciences. This commentary draws on our collective expertise to identify key populations where particular methodological and ethical challenges around consent are encountered, articulate the specific issues arising in each population, summarise ongoing and completed research, and identify targets for future research. Key populations include people with communication or other disabilities, people whose capacity to consent fluctuates, adults who lack the capacity to consent, and adults and children in emergency and urgent care settings. Work is ongoing by the sub-group to create a database of resources, to update NIHR guidance, and to develop proposals to address identified research gaps. CONCLUSION: Collaboration across disciplines, sectors, organisations, and countries is essential if the ethical and methodological challenges surrounding trials involving complex and alternate consent pathways are to be addressed. Explicating these challenges, sharing resources, and identifying gaps for future research is an essential first step. We hope that doing so will serve as a call to action for others seeking ways to address the current consent-based exclusion of underserved populations from trials.

Patient-Reported Outcomes 12 Years after Localized Prostate Cancer Treatment.

BACKGROUND: Long-term patient-reported outcomes are needed to inform treatment decisions for localized prostate cancer. METHODS: Patient-reported outcomes of 1643 randomly assigned participants in the ProtecT (Prostate Testing for Cancer and Treatment) trial were evaluated to assess the functional and quality-of-life impacts of prostatectomy, radiotherapy with neoadjuvant androgen deprivation, and active monitoring. This article focuses on the outcomes of the randomly assigned participants from 7 to 12 years using mixed effects linear and logistic models. RESULTS: Response rates exceeded 80% for most measures. Among the randomized groups over 7 to 12 years, generic quality-of-life scores were similar. Among those in the prostatectomy group, urinary leakage requiring pads occurred in 18 to 24% of patients over 7 to 12 years, compared with 9 to 11% in the active monitoring group and 3 to 8% in the radiotherapy group. In the prostatectomy group, 18% reported erections sufficient for intercourse at 7 years, compared with 30% in the active monitoring and 27% in the radiotherapy groups; all converged to low levels of potency by year 12. Nocturia (voiding at least twice per night) occurred in 34% in the prostatectomy group compared with 48% in the radiotherapy group and 47% in the active monitoring group at 12 years. Fecal leakage affected 12% in the radiotherapy group compared with 6% in the other groups by year 12. The active monitoring group experienced gradual age-related declines in sexual and urinary function, avoiding radical treatment effects unless they changed management. CONCLUSIONS: ProtecT provides robust evidence about continued impacts of treatments in the long term. These data allow patients newly diagnosed with localized prostate cancer and their clinicians to assess the trade-offs between treatment harms and benefits and enable better informed and prudent treatment decisions. (Funded by the UK National Institute for Health and Care Research Health Technology Assessment Programme projects 96/20/06 and 96/20/99; ISRCTN number, ISRCTN20141297; ClinicalTrials.gov number, NCT02044172.)

Feasibility of comparing medical management and surgery (with neurosurgery or stereotactic radiosurgery) with medical management alone in people with symptomatic brain cavernoma - protocol for the Cavernomas: A Randomised Effectiveness (CARE) pilot trial.

INTRODUCTION: The top research priority for cavernoma, identified by a James Lind Alliance Priority setting partnership was 'Does treatment (with neurosurgery or stereotactic radiosurgery) or no treatment improve outcome for people diagnosed with a cavernoma?' This pilot randomised controlled trial (RCT) aims to determine the feasibility of answering this question in a main phase RCT. METHODS AND ANALYSIS: We will perform a pilot phase, parallel group, pragmatic RCT involving approximately 60 children or adults with mental capacity, resident in the UK or Ireland, with an unresected symptomatic brain cavernoma. Participants will be randomised by web-based randomisation 1:1 to treatment with medical management and with surgery (neurosurgery or stereotactic radiosurgery) versus medical management alone, stratified by prerandomisation preference for type of surgery. In addition to 13 feasibility outcomes, the primary clinical outcome is symptomatic intracranial haemorrhage or new persistent/progressive focal neurological deficit measured at 6 monthly intervals. An integrated QuinteT Recruitment Intervention (QRI) evaluates screening logs, audio recordings of recruitment discussions, and interviews with recruiters and patients/parents/carers to identify and address barriers to participation. A Patient Advisory Group has codesigned the study and will oversee its progress. ETHICS AND DISSEMINATION: This study was approved by the Yorkshire and The Humber-Leeds East Research Ethics Committee (21/YH/0046). We will submit manuscripts to peer-reviewed journals, describing the findings of the QRI and the Cavernomas: A Randomised Evaluation (CARE) pilot trial. We will present at national specialty meetings. We will disseminate a plain English summary of the findings of the CARE pilot trial to participants and public audiences with input from, and acknowledgement of, the Patient Advisory Group. TRIAL REGISTRATION NUMBER: ISRCTN41647111.

Understanding the perspectives of recruiters is key to improving randomised controlled trial enrolment: a qualitative evidence synthesis.

BACKGROUND: Recruiting patients to randomised controlled trials (RCTs) is often reported to be challenging, and the evidence base for effective interventions that could be used by staff (recruiters) undertaking recruitment is lacking. Although the experiences and perspectives of recruiters have been widely reported, an evidence synthesis is required in order to inform the development of future interventions. This paper aims to address this by systematically searching and synthesising the evidence on recruiters' perspectives and experiences of recruiting patients into RCTs.  METHODS: A qualitative evidence synthesis (QES) following Thomas and Harden's approach to thematic synthesis was conducted. The Ovid MEDLINE, CINAHL, EMBASE, PsycInfo, Cochrane Central Register of Controlled Trials, ORRCA and Web of Science electronic databases were searched. Studies were sampled to ensure that the focus of the research was aligned with the phenomena of interest of the QES, their methodological relevance to the QES question, and to include variation across the clinical areas of the studies. The GRADE CERQual framework was used to assess confidence in the review findings. RESULTS: In total, 9316 studies were identified for screening, which resulted in 128 eligible papers. The application of the QES sampling strategy resulted in 30 papers being included in the final analysis. Five overlapping themes were identified which highlighted the complex manner in which recruiters experience RCT recruitment: (1) recruiting to RCTs in a clinical environment, (2) enthusiasm for the RCT, (3) making judgements about whether to approach a patient, (4) communication challenges, (5) interplay between recruiter and professional roles. CONCLUSIONS: This QES identified factors which contribute to the complexities that recruiters can face in day-to-day clinical settings, and the influence recruiters and non-recruiting healthcare professionals have on opportunities afforded to patients for RCT participation. It has reinforced the importance of considering the clinical setting in its entirety when planning future RCTs and indicated the need to better normalise and support research if it is to become part of day-to-day practice. TRIAL REGISTRATION: PROSPERO CRD42020141297 (registered 11/02/2020).