Search

Summary: After more than 120 hand‐upper extremity and 37 face transplant procedures performed worldwide, vascularized composite allotransplantation (VCA) now falls under the scope of organ transplant legislation in Europe and the United States. While in the USA, VCA has been considered as standard care since 2014, VCA in Europe is still performed through clinical research trials, except in United Kingdom. However, after two decades of favourable experience with upper extremity transplantation (UET), professionals in Europe are proposing hand allotransplantation as "controlled standard" care, as opposed to face transplantation (FT), which is still a challenging activity. The European Committee on Organ Transplantation (CD‐P‐TO) has elaborated a position paper to provide recommendations concerning regulatory aspects for UET and FT. It is aimed at Health Authorities in charge of the oversight – and coordination – of organ donation and transplantation, and at professional groups to help them manage such complex and costly programs dedicated to properly selected patients. [ABSTRACT FROM AUTHOR]

Background: Use of electronic methods to support informed consent ('eConsent') is increasingly popular in clinical research. This commentary reports the approach taken to implement electronic consent methods and subsequent experiences from a range of studies at the Leeds Clinical Trials Research Unit (CTRU), a large clinical trials unit in the UK. Main text: We implemented a remote eConsent process using the REDCap platform. The process can be used in trials of investigational medicinal products and other intervention types or research designs. Our standard eConsent system focuses on documenting informed consent, with other aspects of consent (e.g. providing information to potential participants and a recruiter discussing the study with each potential participant) occurring outside the system, though trial teams can use electronic methods for these activities where they have ethical approval. Our overall process includes a verbal consent step prior to confidential information being entered onto REDCap and an identity verification step in line with regulator guidance. We considered the regulatory requirements around the system's generation of source documents, how to ensure data protection standards were upheld and how to monitor informed consent within the system. We present four eConsent case studies from the CTRU: two randomised clinical trials and two other health research studies. These illustrate the ways eConsent can be implemented, and lessons learned, including about differences in uptake. Conclusions: We successfully implemented a remote eConsent process at the CTRU across multiple studies. Our case studies highlight benefits of study participants being able to give consent without having to be present at the study site. This may better align with patient preferences and trial site needs and therefore improve recruitment and resilience against external shocks (such as pandemics). Variation in uptake of eConsent may be influenced more by site-level factors than patient preferences, which may not align well with the aspiration towards patient-centred research. Our current process has some limitations, including the provision of all consent-related text in more than one language, and scalability of implementing more than one consent form version at a time. We consider how enhancements in CTRU processes, or external developments, might affect our approach. [ABSTRACT FROM AUTHOR]

Thousands of clinical trials are conducted globally each year. Yet, little is known about their environmental impact. This paper presents the results of a high-level literature review of the carbon footprint of clinical trials. Five papers were identified and their contents summarised qualitatively. All papers were authored by UK researchers. Carbon footprint metrics from 14 trials were presented in carbon dioxide equivalents (CO2e). Emissions were broken down by three broadly defined clinical trial activities: operations, travel, and supplies. Recommen - dations for carbon reduction are discussed. The review showed a dearth of publications on greenhouse gas emissions generated by clinical trials. More work in this area is needed to achieve sustainable, low carbon clinical research. [ABSTRACT FROM AUTHOR]

The author reports on the discussion of the white paper on adaptive dose-ranging designs by the Phrma working Group in Great Britain. He states that the discussion is focusing on methodological issues and drug development. He stresses out that the white paper conducts simulations to compare a traditional approach with alternative design-focused and analysis-focused approaches. He also discusses the different level of phases on the pre-clinical trials.

Summary: Over a decade ago, bibliometric analysis predicted the disappearance of UK publishing in anaesthesia by 2020. We repeated this analysis to assess if this had turned out to be the case, searching PubMed for papers associated with UK consultant anaesthetists for 2017–2019 across 15 journals. Although the rate of decline has flattened using the same search filter, including a wider range of publication types shows that outputs still remain at half 1990s levels (381 papers for all 3 years combined), authored by 769 anaesthetists, 274 of whom are associated with an academic centre. There are now 11 identifiable academic units, and a further 15 places where anaesthetists have affiliations with academic centres as individuals. The majority of papers (71%) are in secondary analysis (observational, database and association studies, surveys and meta‐analyses), rather than in primary research (clinical trials or laboratory studies). These data reflect the current academic capacity in terms of publications, academic units and staffing. We discuss how this information can be used to inform a new strategy for UK academic anaesthesia. [ABSTRACT FROM AUTHOR]

Background: Stroke survivors with aphasia want to improve their everyday talking (discourse). In current UK practice, 90% of speech and language therapists believe discourse assessment and treatment is part of their role but are hampered by barriers in resources, time and expertise. There is a clinical need for well-articulated discourse assessment and treatments. LUNA is a multi-level treatment targeting words, sentences and discourse macrostructure in personal stories that addresses this clinical need. Objectives: This study aimed to assess the feasibility and acceptability of LUNA trial procedures in a randomised waitlist-controlled trial; and to evaluate preliminary efficacy. Methods: This paper reports a phase II, waitlist-controlled, proof-of-concept feasibility trial. Participants with chronic aphasia (n = 28) were recruited from the community and randomised to an Immediate (n = 14) or Delayed (n = 14) group. LUNA treatment was delivered twice weekly for 10 weeks via the videoconferencing technology, Zoom. Feasibility was assessed in terms of participant recruitment and retention, adherence, missing data, and treatment fidelity. Preliminary treatment efficacy was assessed in terms of between group differences in outcome measures relating to discourse, language, and psychosocial state. Results: The remote LUNA trial was feasible: 85% of those eligible consented to the trial; trial retention was 86%; 87% of treatment sessions were delivered as scheduled, and 79% of participants completed 80%+ of the treatment programme; data was missing only for participants who withdrew; treatment fidelity was high at 92% adherence; and only one clinical outcome measure demonstrated ceiling effects. ANCOVA analysis of the clinical outcome measures revealed group differences with medium and large effect sizes, indicating, improvements in the production of words, sentences, discourse macrostructure, overall language functioning (WAB-R), and psychosocial state (VAMS) following LUNA treatment. For most outcomes measured, similar treatment benefits were suggested in a secondary, non-parametric analysis. Conclusions: Large-scale evaluation of the clinical efficacy and cost-effectiveness of LUNA is warranted and supported by these findings. Trial registration: Clinical trials registration: NCT05847023 (clinical trials.gov). [ABSTRACT FROM AUTHOR]

The article presents a meta-ethnographic synthesis study on the reasons of people for participating in clinical trials. It mentions the application of an interpretative translation process for analyzing the link between findings. It also notes that the line of argument of the synthesis conducted in 2005 and 2010 indicated how the health states and medical care status of participants interact with other considerations.

The article presents abstracts on medical topics which include the gastroscopy rate in general practitioner practice populations in Great Britain, randomised prospective trial of transnasal and standard upper diagnostic endoscopy under local anesthetic, and guidelines on the endoscopic assessment of gastric polyps.

The COVID-19 pandemic has affected how clinical trials are managed, both within existing portfolios and for the rapidly developed COVID-19 trials. Sponsors or delegated organisations responsible for monitoring trials have needed to consider and implement alternative ways of working due to the national infection risk necessitating restricted movement of staff and public, reduced clinical staff resource as research staff moved to clinical areas, and amended working arrangements for sponsor and sponsor delegates as staff moved to working from home.Organisations have often worked in isolation to fast track mitigations required for the conduct of clinical trials during the pandemic; this paper describes many of the learnings from a group of monitoring leads based in United Kingdom Clinical Research Collaboration (UKCRC) Clinical Trials Unit (CTUs) within the UK.The UKCRC Monitoring Task and Finish Group, comprising monitoring leads from 9 CTUs, met repeatedly to identify how COVID-19 had affected clinical trial monitoring. Informed consent is included as a specific issue within this paper, as review of completed consent documentation is often required within trial monitoring plans (TMPs). Monitoring is defined as involving on-site monitoring, central monitoring or/and remote monitoring.Monitoring, required to protect the safety of the patients and the integrity of the trial and ensure the protocol is followed, is often best done by a combination of central, remote and on-site monitoring. However, if on-site monitoring is not possible, workable solutions can be found using only central or central and remote monitoring. eConsent, consent by a third person, or via remote means is plausible. Minimising datasets to the critical data reduces workload for sites and CTU staff. Home working caused by COVID-19 has made electronic trial master files (TMFs) more inviting. Allowing sites to book and attend protocol training at a time convenient to them has been successful and worth pursuing for trials with many sites in the future.The arrival of COVID-19 in the UK has forced consideration of and changes to how clinical trials are conducted in relation to monitoring. Some developed practices will be useful in other pandemics and others should be incorporated into regular use. [ABSTRACT FROM AUTHOR]

Aim: Neurodevelopment is a key outcome for many childhood trials and observational studies. Clinically important decisions may rest on finding relatively small differences in neurodevelopment between groups receiving complex and costly interventions. Our purpose was to determine whether studies which measure neurodevelopment report the numbers, training, and auditing of assessors and, for multiple assessor studies, whether the results were adjusted and if so by which method?Method: Electronic searches were conducted using Medline, Embase, Cinahl, PsycINFO, and the Cochrane Library. A study was eligible if it reported neurodevelopmental outcome in children resident in the UK, less than or equal to 18 years and was published between 2000 and 2015. Trials and observational studies were included.Results: Three hundred and seven full papers were reviewed: 52% of papers did not report the number of assessors used; 21% used a single assessor; and 27% used multiple assessors. Thirty-five per cent mentioned that assessors were trained in the use of the neurodevelopmental tool; 13% of assessors were audited; and only 1% of studies adjusted statistically for the number of assessors.Interpretation: At the very least, the quality of reporting the use of assessors in these research publications is poor, while at worst, the variability of assessors may mask the true relationship between an intervention/observation and neurodevelopmental outcome. [ABSTRACT FROM AUTHOR]

Plain English summary: Patient and Public Involvement (PPI) describes the active involvement of patients and the public in the research process. Through PPI, patients and members of the public are increasingly involved in the design and conduct of clinical trials. PPI has been shown to improve the quality and relevance of research. During the COVID-19 pandemic, clinical trials have been playing a vital role in helping us find ways to prevent and treat the infection and improve our understanding of the virus. It is important that patients and the public are actively involved in deciding how COVID-19 research is carried out. Unfortunately, Research Ethics Committees in the UK have seen far less PPI for COVID-19 research studies compared with research before the pandemic. A key reason for this is that research is being designed much faster than normal and researchers may feel they do not have time to properly involve patients and the public. In this paper, we share our experiences of PPI for a COVID-19 clinical trial. We show that it is possible to rapidly involve patients and the public in COVID-19 clinical trials. We also explain how the design of the clinical trial was changed in response to feedback from public contributors. Lastly, we discuss the wider learning from this process which might be useful for researchers planning PPI activities for COVID-19 clinical trials in the future. Background: Clinical trials are playing a critical role in the global public health response to the COVID-19 pandemic. Despite the increasing recognition of the value of PPI in clinical trials, just 22% of the COVID-19 research proposals reviewed by Research Ethics Committees in the UK at the start of the pandemic reported PPI. There is a perception that PPI might result in delays in delivering research and therefore delays in obtaining important results. In this paper, we report our experience of rapid PPI for a COVID-19 clinical trial. Methods: RAPID-19 is a COVID-19 clinical trial which was planned to be submitted for fast-track ethics review in the United Kingdom. During the development of the trial protocol, the PPI Panel at the London School of Hygiene & Tropical Medicine Clinical Trials Unit was involved in the design of the study. The meeting with the PPI Panel lasted just over 1 h and was conducted by teleconference. Results: Although we only had a short period of time to explore the study with the PPI Panel, we were able to gain valuable insight into how the trial would be perceived by potential trial participants. Substantive changes were made to the trial to improve the acceptability of the research without compromising the study timelines. Having access to public contributors with relevant lived experience is an important resource for a Clinical Trials Unit and is critical for rapid PPI. The move to remote working due to lockdown required virtual discussions which helped to overcome some of the barriers to organising face-to-face meetings at short notice. Conclusions: PPI for clinical trials can be conducted in a time-efficient manner within the pressured environment of a pandemic. Involving PPI contributors at an early stage in protocol development maximised the opportunity to shape and influence the trial as well as limited potential delays which could occur if changes to the protocol had to be made at a later stage. [ABSTRACT FROM AUTHOR]

With the globalization of clinical trials, regulators have increased collaboration to evaluate the adequacy of clinical trial conduct and to optimize regulatory oversight. The 2020 joint Good Clinical Practice (GCP) symposium of the US Food and Drug Administration and the UK Medicines and Healthcare products Regulatory Agency provided the agencies' perspectives on the challenges in ensuring data quality in novel clinical trial designs and the importance of the management and documentation of protocol deviations, sponsor oversight of clinical trials, and use of electronic source data, including electronic health records. This paper summarizes considerations of both agencies on these topics, along with case examples. This paper touches upon considerations when using real‐world data to support regulatory decisions. It also discusses the impact of the coronavirus disease 2019 (COVID‐19) pandemic on clinical trial conduct and underscores the importance of well‐designed, resilient, and adaptable systems for GCP compliance and data integrity. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has presented unique challenges for rapidly designing, initiating, and delivering therapeutic clinical trials. PRINCIPLE (Platform Randomised Trial of Treatments in the Community for Epidemic and Pandemic Illnesses) is the UK national platform investigating repurposed therapies for COVID-19 treatment of older people in the community at high risk of complications. Standard methods of patient recruitment were failing to meet the required pace and scale of enrolment. This paper describes the development and appraisal of a near real-time, data-driven, ethical approach for enhancing recruitment in community care by contacting people with a recent COVID-19 positive test result from the central NHS Test and Trace service within approximately 24-48 h of their test result.Methods: A multi-disciplinary team was formed to solve the technical, ethical, public perception, logistical and information governance issues required to provide a near-real time (approximately within 24-48 h of receiving a positive test) feed of potential trial participants from test result data to the research team. PRINCIPLE was also given unique access to the Summary Care Record (SCR) to ensure safe prescribing, and to enable the trial team to quickly and safely bring consented patients into the trial. A survey of the public was used to understand public perceptions of the use of test data for this proposed methodology.Results: Prior to establishing the data service, PRINCIPLE registered on average 87 participants per week. This increased by up to 87 additional people registered per week from the test data, contributing to an increase from 1013 recruits to PRINCIPLE at the start of October 2020 to 2802 recruits by 20 December 2020. Whilst procedural caveats were identified by the public consultation, out of 2639 people contacted by PRINCIPLE following a positive test result, no one raised a concern about being approached.Conclusions: This paper describes a novel approach to using near-real time NHS operational data to recruit community-based patients within a few days of presentation with acute illness. This approach increased recruitment and reduced time between positive test and randomisation, allowing more rapid evaluation of treatments and increased safety for participants. End-to-end public and patient involvement in the design of the approach provided evidence to inform information governance decisions.Trial Registration: PRINCIPLE is funded by UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research. EudraCT number: 2020-001209-22 . 26/03/2020 ISRCTN registry: ISRCTN86534580 . 20/03/2020 REC number: 20/SC/058 IRAS number: 281958. [ABSTRACT FROM AUTHOR]

Background: Dysarthria after stroke is when speech intelligibility is impaired, and this occurs in half of all stroke survivors. Dysarthria often leads to social isolation, poor psychological well-being and can prevent return to work and social lives. Currently, a variety of outcome measures are used in clinical research and practice when monitoring recovery for people who have dysarthria. When research studies use different measures, it is impossible to compare results from trials and delays our understanding of effective clinical treatments. The aim of this study is to develop a core outcome set (COS) to agree what aspects of speech recovery should be measured for dysarthria after stroke (COS-Speech) in research and clinical practice. Methods: The COS-Speech study will include five steps: (1) development of a long list of possible outcome domains of speech that should be measured to guide the survey; (2) recruitment to the COS-Speech study of three key stakeholder groups in the UK and Australia: stroke survivors, communication researchers and speech and language therapists/pathologists; (3) two rounds of the Delphi survey process; (4) a consensus meeting to agree the speech outcomes to be measured and a follow-up consensus meeting to match existing instruments/measures (from parallel systematic review) to the agreed COS-Speech; (5) dissemination of COS-Speech. Discussion: There is currently no COS for dysarthria after stroke for research trials or clinical practice. The findings from this research study will be a minimum COS, for use in all dysarthria research studies and clinical practice looking at post-stroke recovery of speech. These findings will be widely disseminated using professional and patient networks, research and clinical forums as well as using a variety of academic papers, videos, accessible writing such as blogs and links on social media. Trial registration: COS-Speech is registered with the Core Outcome Measures in Effectiveness Trials (COMET) database, October 2021 https://www.comet-initiative.org/Studies/Details/1959. In addition, "A systematic review of the psychometric properties and clinical utility of instruments measuring dysarthria after stroke" will inform the consensus meeting to match measures to COS-Speech. The protocol for the systematic reviews registered with the International Prospective Register of Systematic Reviews. PROSPERO registration number: CRD42022302998. [ABSTRACT FROM AUTHOR]

Objective: This paper presents the findings of a study evaluating the effectiveness, accessibility, sustainability and patient satisfaction of the Assessment PLUS model. This model aimed to reduce patients' symptomology, improve their functioning and alleviate the demand on Psychological Therapies Team (PTT) staff, particularly in response to the challenges posed by the COVID‐19 pandemic. Methods: The intervention was offered to 55 patients with mild‐to‐moderate mental health conditions across three localities in Lanarkshire, UK, of whom only 25 completed the sessions. Clinical outcome measure scores, patients' feedback, wait times, discharge, returning patients and re‐referral rates were analysed using a mixed methods approach. Results: The results of the statistical analysis highlight a statistically significant improvement (p < 0.001) in patients' presentations and results of the thematic analysis reveal that almost all patients found the intervention helpful and returned overall positive feedback. On completing the intervention, less than a third of patients returned to the waiting list, while more than half were discharged completely. At the 6‐month follow‐up, those returning to the PTT waitlists (n = 12) had between 6 and 8 sessions on average, while over the 80% of those discharged from A+ did not require further psychological input. The average wait time across the full sample was 6 weeks. Conclusions: In summary, the results of the mixed methods analysis demonstrate a significant improvement in patients' presentations after completing the A+ intervention. The majority of patients found the intervention helpful and provided positive feedback. Moreover, a significant proportion of patients were discharged completely, and those who returned to the PTT waitlists required fewer sessions on average. The average wait time for the full sample was just over 6 weeks. [ABSTRACT FROM AUTHOR]

Background: The E-Freeze trial is a multi-centre randomised controlled trial of fresh versus frozen embryo transfer for women undergoing in vitro fertilisation. This paper describes the statistical analysis plan for the E-Freeze trial.Methods and Design: E-Freeze is a two-arm parallel-group, multi-centre, individually randomised controlled trial to determine if a policy of freezing embryos, followed by thawed frozen embryo transfer, results in a higher healthy baby rate when compared with the current policy of transferring fresh embryos. Couples undergoing their first, second or third cycle of in vitro fertilisation at fertility centres in the UK were randomised to either fresh or frozen embryo transfer. The primary outcome is a healthy baby, defined as a live singleton baby born at term with an appropriate weight for gestation. This paper describes the statistical analysis plan for the trial, including the analysis principles, definitions of outcomes, methods for primary analysis, pre-specified subgroup analysis and sensitivity analysis. This plan was finalised prior to completion of recruitment to the trial.Trial Registration: ISRCTN registry: ISRCTN61225414 . Registered on 29 December 2015. [ABSTRACT FROM AUTHOR]

Physical inactivity has been identified as a leading risk factor for premature mortality globally, and adolescents, in particular, have low physical activity levels. Schools have been identified as a setting to tackle physical inactivity. Economic evidence of school-based physical activity programmes is limited, and the costs of these programmes are not always collected in full. This paper describes a micro-costing and cost-consequence analysis of the ‘Girls Active’ secondary school-based programme as part of a cluster randomised controlled trial (RCT). Micro-costing and cost-consequence analyses were conducted using bespoke cost diaries and questionnaires to collect programme delivery information. Outcomes for the cost-consequence analysis included health-related quality of life measured by the Child Health Utility-9D (CHU-9D), primary care General Practitioner (GP) and school-based (school nurse and school counsellor) service use as part of a cluster RCT of the ‘Girls Active’ programme. Overall, 1,752 secondary pupils were recruited and a complete case sample of 997 participants (Intervention n = 570, Control n = 427) was used for the cost-consequence analysis. The micro-costing analysis demonstrated that, depending upon how the programme was delivered, ‘Girls Active’ costs ranged from £1,054 (£2 per pupil, per school year) to £3,489 (£7 per pupil, per school year). The least costly option was to absorb ‘Girls Active’ strictly within curriculum hours. The analysis demonstrated no effect for the programme for the three main outcomes of interest (health-related quality of life, physical activity and service use).Micro-costing analyses demonstrated the costs of delivering the ‘Girls Active’ programme, addressing a gap in the United Kingdom (UK) literature regarding economic evidence from school-based physical activity programmes. This paper provides recommendations for those gathering cost and service use data in school settings to supplement validated and objective measures, furthering economic research in this field. Trial registration: -ISRCTN, . [ABSTRACT FROM AUTHOR]

Background: During the COVID-19 pandemic, in-person healthcare visits were reduced. Consequently, trial teams needed to consider implementing remote methods for conducting clinical trials, including e-Consent. Although some clinical trials may have implemented e-Consent prior to the pandemic, anecdotes of uptake for this method increased within academic-led trials. When the increased use of this process emerged, representatives from several large academic clinical trial groups within the UK collaborated to discuss ways in which trialists can learn from one another when implementing e-Consent. Methods: A survey of UKCRC-registered Clinical Trials Units (CTUs) was undertaken in April–June 2021 to understand the implementation of and their views on the use of e-Consent and experiences from the perspectives of systems programmers and quality assurance staff on the use of e-Consent. CTUs not using e-Consent were asked to provide any reasons/barriers (including no suitable trials) and any plans for implementing it in the future. Two events for trialists and patient and public involvement (PPI) representatives were then held to disseminate findings, foster discussion, share experiences and aid in the identification of areas that the academic CTU community felt required more research. Results: Thirty-four (64%) of 53 CTUs responded to the survey, with good geographical representation across the UK. Twenty-one (62%) of the responding CTUs had implemented e-Consent in at least one of their trials, across different types of trials, including CTIMPs (Clinical Trial of Investigational Medicinal Product), ATIMPs (Advanced Therapy Medicinal Products) and non-CTIMPs. One hundred ninety-seven participants attended the two workshops for wide-ranging discussions. Conclusion: e-Consent is increasingly used in academic-led trials, yet uncertainties remain amongst trialists, patients and members of the public. Uncertainties include a lack of formal, practical guidance and a lack of evidence to demonstrate optimal or appropriate methods to use. We strongly encourage trialists to continue to share their own experiences of the implementation of e-Consent. [ABSTRACT FROM AUTHOR]

Background: Melanoma incidence has quadrupled since 1970 and melanoma is now the second most common cancer in individuals under 50. Targeted immunotherapies for melanoma now potentially enable long-term remission even in advanced melanoma, but these melanoma survivors require ongoing surveillance, with implications for NHS resources and significant social and psychological consequences for patients. Total skin self-examination (TSSE) can detect recurrence earlier and improve clinical outcomes but is underperformed in the UK. To support survivors, the Achieving Self-directed Integrated Cancer Aftercare (ASICA) intervention was developed to prompt and improve TSSE performance, with subsequent reporting of concerns and submission of skin photos to a Dermatology Nurse Practitioner (DNP). ASICA was delivered as a randomized pilot trial.Methods: This paper reports on process evaluation. Data on participants' demographics and the concerns they reported during the trial were tabulated and displayed using Microsoft Excel and SPSS. We explored which participants used ASICA, and how frequently, to report any skin concerns. We also determined how the interactions had worked in terms of quality of skin photographs submitted, clinical assessments made by the DNP, and the assessments and decisions made for each concern. Finally, we explored significant events occurring during the trial. Data on participants' demographics and the concerns they reported during the trial were tabulated and displayed using SPSS. A semi-structured interview was undertaken with the DNP to gain perspective on the range of concerns presented and how they were resolved.Results: Of 121 recruited melanoma patients receiving ASICA for 12 months, 69 participants submitted a total of 123 reports detailing 189 separate skin-related concerns and including 188 skin photographs. Where participants fully complied with follow-up by the DNP, concerns were usually resolved remotely, but 19 (10.1%) were seen at a secondary care clinic and 14 (7.4%) referred to their GP. 49 (25.9%) of concerns were not completely resolved due to partial non-compliance with DNP follow-up.Conclusion: Melanoma patients randomized to the ASICA intervention were able to report skin-related concerns that could be resolved remotely through interaction with a DNP. Feasibility issues highlighted by ASICA will support further development and optimization of this digital tool.Trial Registration: Clinical Trials.gov , NCT03328247 . Registered on 1 November 2017. [ABSTRACT FROM AUTHOR]

Background: Advancing physical therapy interventions for children and young people is a high research priority. This includes research to describe and specify the control condition, typically 'current care', for effectiveness trials. This paper aims to identify physical therapy outcomes commonly targeted, and intervention techniques and approaches commonly used, by physiotherapists working with children (aged 2–19 years) with mobility limitations in the United Kingdom. Methods: A cross‐sectional survey. Participants were recruited through the interactive Chartered Society of Physiotherapy members‐only online discussion forum, the Association of Paediatric Chartered Physiotherapists, direct emails and snowball sampling within the authors' professional networks and Twitter. Data were collected using a structured online questionnaire and analysed using descriptive statistics. Results: We received 146 responses, 95/146 (65.1%) of which were fully complete. Therapists reported targeting 367 unique outcome constructs, of which 193 (52.6%) mapped onto activities and participation (e.g. moving around using equipment, maintaining body position and walking), 158 (43.1%) on body functions (e.g. muscle strength, joint mobility and gait functions), 11 (3.0%) on body structure (e.g. muscle length) and 3 (0.8%) on environmental factors (e.g. access home environment, access school environment and family confidence). The most commonly used interventions related to postural management (115/133 of respondents, 86.4%) and exercise therapy (116/137, 84.67%) and included techniques such as 'use equipment' (118/137, 86.1%), 'instruct how to do something' (117/137, 85.4%), 'practice' (105/137, 76.6%) and 'stretch' (99/137, 72.3%). Conclusions: In designing trials, current care can be described as a combination of biomechanical and physiological techniques and approaches targeted at body functions and through that to activity and participation. Although some environmental behaviour change techniques and strategies were reported, the explicit use of these in current care appears limited. [ABSTRACT FROM AUTHOR]

Background: Routinely collected electronic health records (EHRs) have the potential to enhance randomised controlled trials (RCTs) by facilitating recruitment and follow-up. Despite this, current EHR use is minimal in UK RCTs, in part due to ongoing concerns about the utility (reliability, completeness, accuracy) and accessibility of the data. The aim of this manuscript is to document the process, timelines and challenges of the application process to help improve the service both for the applicants and data holders.Methods: This is a qualitative paper providing a descriptive narrative from one UK clinical trials unit (MRC CTU at UCL) on the experience of two trial teams' application process to access data from three large English national datasets: National Cancer Registration and Analysis Service (NCRAS), National Institute for Cardiovascular Outcomes Research (NICOR) and NHS Digital to establish themes for discussion. The underpinning reason for applying for the data was to compare EHRs with data collected through case report forms in two RCTs, Add-Aspirin (ISRCTN 74358648) and PATCH (ISRCTN 70406718).Results: The Add-Aspirin trial, which had a pre-planned embedded sub-study to assess EHR, received data from NCRAS 13 months after the first application. In the PATCH trial, the decision to request data was made whilst the trial was recruiting. The study received data after 8 months from NICOR and 15 months for NHS Digital following final application submission. This concluded in May 2020. Prior to application submission, significant time and effort was needed particularly in relation to the PATCH trial where negotiations over consent and data linkage took many years.Conclusions: Our experience demonstrates that data access can be a prolonged and complex process. This is compounded if multiple data sources are required for the same project. This needs to be factored in when planning to use EHR within RCTs and is best considered prior to conception of the trial. Data holders and researchers are endeavouring to simplify and streamline the application process so that the potential of EHR can be realised for clinical trials. [ABSTRACT FROM AUTHOR]

This paper examines the introduction to Britain of the Gräfenberg ring, an early version of what later became known as an intrauterine device (IUD). The struggle during the interwar years to establish the value of the ring provides an opportunity for a case study of the evaluation and acceptance of a new medical device. With the professionalization of the birth control movement and the expansion of birth control clinics in interwar Britain, efforts to develop better scientific means for contraception grew rapidly. At the end of the nineteenth century, methods for controlling fertility ranged from coitus interruptus and abstinence, to diverse substances ingested or placed into the vagina, to barrier methods. The first decades of the twentieth century brought early work on chemical contraceptives as well as a number of new intrauterine devices, among them the Gräfenberg ring. Developing a cheap, reliable, and widely acceptable contraceptive became a pressing goal for activists in the voluntary birth control movement in Britain between the wars. Yet, tensions developed over the best form of contraception to prescribe. By situating the Gräfenberg ring within the context of the debates and competition among British medical and birth control professionals, this paper reveals broader issues of power relationships and expertise in the assessment of a new medical technology. [ABSTRACT FROM AUTHOR]

Background: There is little published guidance as to the sample size required for a pilot or feasibility trial despite the fact that a sample size justification is a key element in the design of a trial. A sample size justification should give the minimum number of participants needed in order to meet the objectives of the trial. This paper seeks to describe the target sample sizes set for pilot and feasibility randomised controlled trials, currently running within the United Kingdom. Methods: Data were gathered from the United Kingdom Clinical Research Network (UKCRN) database using the search terms 'pilot' and 'feasibility'. From this search 513 studies were assessed for eligibility of which 79 met the inclusion criteria. Where the data summary on the UKCRN Database was incomplete, data were also gathered from: the International Standardised Randomised Controlled Trial Number (ISRCTN) register; the clinicaltrials.gov website and the website of the funders. For 62 of the trials, it was necessary to contact members of the research team by email to ensure completeness. Results: Of the 79 trials analysed, 50 (63.3%) were labelled as pilot trials, 25 (31.6%) feasibility and 14 were described as both pilot and feasibility trials. The majority had two arms (n = 68, 86.1%) and the two most common endpoints were continuous (n = 45, 57.0%) and dichotomous (n = 31, 39.2%). Pilot trials were found to have a smaller sample size per arm (median = 30, range = 8 to 114 participants) than feasibility trials (median = 36, range = 10 to 300 participants). By type of endpoint, across feasibility and pilot trials, the median sample size per arm was 36 (range = 10 to 300 participants) for trials with a dichotomous endpoint and 30 (range = 8 to 114 participants) for trials with a continuous endpoint. Publicly funded pilot trials appear to be larger than industry funded pilot trials: median sample sizes of 33 (range = 15 to 114 participants) and 25 (range = 8 to 100 participants) respectively. Conclusion: All studies should have a sample size justification. Not all studies however need to have a sample size calculation. For pilot and feasibility trials, while a sample size justification is important, a formal sample size calculation may not be appropriate. The results in this paper describe the observed sample sizes in feasibility and pilot randomised controlled trials on the UKCRN Database. [ABSTRACT FROM AUTHOR]

Background: Trial oversight is important for trial governance and conduct. Patients and/or lay members of the public are increasingly included in trial oversight committees, influenced by international patient and public involvement (PPI) initiatives to improve the quality and relevance of research. However, there is a lack of guidance on how to undertake PPI in trial oversight and tokenistic PPI remains an issue. This paper explores how PPI functions in existing trial oversight committees and provides recommendations to optimise PPI in future trials. This was part of a larger study investigating the role and function of oversight committees in trials facing challenges.Methods: Using an ethnographic study design, we observed oversight meetings of eight UK trials and conducted semi-structured interviews with members of their trial steering committees (TSCs) and trial management groups (TMGs) including public contributors, trial sponsors and funders. Thematic analysis of data was undertaken, with findings integrated to provide a multi-perspective account of how PPI functions in trial oversight.Results: Eight TSC and six TMG meetings from eight trials were observed, and 66 semi-structured interviews conducted with 52 purposively sampled oversight group members, including three public contributors. PPI was reported as beneficial in trial oversight, with public members contributing a patient voice and fulfilling a patient advocacy role. However, public contributors were not always active at oversight meetings and were sometimes felt to have a tokenistic role, with trialists reporting a lack of understanding of how to undertake PPI in trial oversight. To optimise PPI in trial oversight, the following areas were highlighted: the importance of planning effective strategies to recruit public contributors; considering the level of oversight and stage(s) of trial to include PPI; support for public contributors by the trial team between and during oversight meetings.Conclusions: We present evidence-based recommendations to inform future PPI in trial oversight. Consideration should be given at trial design stage on how to recruit and involve public contributors within trial oversight, as well as support and mentorship for both public contributors and trialists (in how to undertake PPI effectively). Findings from this study further strengthen the evidence base on facilitating meaningful PPI within clinical trials. [ABSTRACT FROM AUTHOR]

The aim of our research project, described in this paper, was to develop a purpose-built clinical trials support system [CTSS], which would be sufficiently comprehensive, integrated and flexible, so as to support the vast majority of research studies that were to be managed and conducted by one UK-based health authority. Whilst at the start of this project, it was reasonably clear what major clinical activities the system would need to be able to support, it was less clear what benefits the system should be expected to deliver, nor how these benefits were related to specific aspects of the system's functionality. Moreover, whilst it was recognised that the introduction of the CTSS would engender fairly significant organisational changes, it was less easy to articulate the nature of the changes, nor how they might ultimately relate to the realisation of benefits. Consequently, it was agreed at the project's outset that an explicit benefits' realisation approach should be integrated into the system's development activity. The aims of this paper are threefold: 1] to describe the CTSS project, paying particular attention to why it justified the inclusion of a benefits realisation approach; 2] to provide a description of, and justification for, the benefits management approach adopted; 3] to provide a provisional assessment of the effectiveness of this approach. In addressing these objectives, it was envisaged that our paper would make an important contribution to the literature by providing one of the few first-hand accounts of the conduct of benefits' management practices, and certainly the first in the context of clinical trials support systems. Moreover, the paper provides new insights into the integration of benefits realisation and structured development tools and practices: we describe how the benefits dependency network has been successfully related to use case diagrams. [ABSTRACT FROM AUTHOR]

Background: The incidence of chronic subdural haematoma (CSDH) is increasing. Although surgery remains the mainstay of management for symptomatic patients, uncertainty remains regarding the role of steroids. Hence, the Dex-CSDH trial was launched in the UK in 2015 aiming to determine whether, compared to placebo, dexamethasone can improve the 6-month functional outcome of patients with symptomatic CSDH by reducing the rate of surgical intervention and recurrence rate.Methods and Design: Dex-CSDH is a multi-centre, pragmatic, parallel group, double-blind, randomised trial assessing the clinical utility of a 2-week course of dexamethasone following a CSDH. Seven hundred fifty patients were randomised to either dexamethasone or placebo. The primary outcome is the modified Rankin Scale at 6 months which is dichotomised to favourable (a score of 0-3) versus unfavourable (a score of 4-6).Conclusions: This paper and the accompanying additional material describe the statistical analysis plan for the trial.Trial Registration: ISRCTN, ISRCTN80782810. Registered on 7 November 2014. http://www.isrctn.com/ISRCTN80782810. EudraCT, 2014-004948-35. Registered on 20 March 2015. [ABSTRACT FROM AUTHOR]

This paper examines the role of clinical trials in regenerative medicine innovation, exploring how trials have contributed to translational challenges in the field. Using data from an ethnographic study of UK cell therapy trials I interrogate the institutional framework for clinical trials and the identity-making of trialists. This analysis uncovers a disconnect between a commercially-aligned regulatory framework and a clinical-academic identity apparent in the majority of current trialling activity. These different pathways appear to represent two distinct sociotechnical imaginaries for cell therapies; one which reflects the assumptions of commercial innovation and prioritizes economic success, and another which embodies the cultural expectations of academia and emphasizes the importance of clinical care. These two imaginaries operate in synergy to some extent but there are significant tensions between them. How and to what extent these tensions are reconciled is likely to determine both the long-term success and the future shape of the field. [ABSTRACT FROM AUTHOR]

International efforts to minimize coercive practices include the US Six Core Strategies© (6CS). This innovative approach has limited evidence of its effectiveness, with few robustly designed studies, and has not been formally implemented or evaluated in the UK. An adapted version of the 6CS, which we called 'REsTRAIN Yourself' (RY), was devised to suit the UK context and evaluated using mixed methods. RY aimed to reduce the use of physical restraint in mental health inpatient ward settings through training and practice development with whole teams, directly in the ward settings where change was to be implemented and barriers to change overcome. In this paper, we present qualitative findings that report on staff perspectives of the impact and value of RY following its implementation. Thirty‐six staff participated in semi‐structured interviews with data subject to thematic analysis. Eight themes are reported that highlight perceived improvements in every domain of the 6CS after RY had been introduced. Staff reported more positively on their relationships with service users and felt their attitudes towards the use of coercive practices such as restraint were changed; the service as a whole shifted in terms of restraint awareness and reduction; and new policies, procedures, and language were introduced despite certain barriers. These findings need to be appreciated in a context wherein substantial reductions in the use of physical restraint were proven possible, largely due to building upon empathic and relational alternatives. However, yet more could be achieved with greater resourcing of inpatient care. [ABSTRACT FROM AUTHOR]

As the cost of clinical trials continues to rise organisations are looking at ways of managing this part of the drug development process as effectively and efficiently as possible. As a tactical response, many pharmaceutical companies outsource the management of clinical trials to clinical research organisations on a fixed-price contract basis. This paper presents an alternative approach based on the concept of Product-Based Planning. Key elements of the approach are the creation of a deliverables budget and the establishment of project management-related deliverables. The conceptual developments described in the paper are supported by a telephone survey of 10 UK practitioners. The survey confirms the prevalence and limitations of fixed-price contracts while highlighting a willingness to try a deliverable-based approach – initially through small pilot studies. The key barrier to implementing a new approach is resistance from key stakeholders, such as finance departments, which can be addressed through selling of the business case. [ABSTRACT FROM AUTHOR]

Randomised controlled trials (RCTs) are considered to be the gold standard in evaluating medical interventions; however, people from ethnic minorities are frequently under-represented in such studies. The present paper addresses a previously neglected debate about the tensions which inform clinical trial participation amongst people from ethnic minorities, in particular, South Asians, the largest ethnic minority group in the UK. In a narrative review of the available literature, based mainly on US studies, the present authors aim to make sense of the issues around under-representation by providing a theoretical reconciliation. In addition, they identify a number of potential barriers to ethnic minority participation in clinical trials. In so doing, the authors recognise that the recent history of eugenic racism, and more general views on clinical trials as a form of experimentation, means that clinical trial participation among people from ethnic minorities becomes more problematic. Lack of participation and the importance of representational sampling are also considered, and the authors argue that health professionals need to be better informed about the issues. The paper concludes by offering a number of strategies for improving ethnic minority accrual rates in clinical trials, together with priorities for future research. [ABSTRACT FROM AUTHOR]

Background: Approximately 40% of treated head and neck cancer (HNC) patients develop recurrence. The risk of recurrence declines with time from treatment. Current guidelines recommend clinical follow-up every two months for the first two years after treatment, with reducing intensity over the next three years. However, evidence for the effectiveness of these regimes in detecting recurrence is lacking, with calls for more flexible, patient-centred follow-up strategies. Methods: PETNECK2 is a UK-based multi-centre programme examining a new paradigm of follow-up, using positron emission tomography-computed tomography (PET-CT)-guided, symptom-based, patient-initiated surveillance. This paradigm is being tested in a unblinded, non-inferiority, phase III, randomised controlled trial (RCT). Patients with HNC, one year after completing curative intent treatment, with no clinical symptoms or signs of loco-regional or distant metastasis will be randomised using a 1:1 allocation ratio to either regular scheduled follow-up, or to PET-CT guided, patient-initiated follow-up. Patients at a low risk of recurrence (negative PET-CT) will receive a face-to-face education session along with an Information and Support (I&S) resource package to monitor symptoms and be in control of initiating an urgent appointment when required. The primary outcome of the RCT is overall survival. The RCT also has an in-built pilot, a nested QuinteT Recruitment Intervention (QRI), and a nested mixed-methods study on patient experience and fear of cancer recurrence (FCR). An initial, single-arm feasibility study has been completed which determined the acceptability of the patient-initiated surveillance intervention, the completion rates of baseline questionnaires, and optimised the I&S resource prior to implementation in the RCT. Discussion: We hypothesise that combining an additional 12-month post-treatment PET-CT scan and I&S resource will both identify patients with asymptomatic recurrence and identify those at low risk of future recurrence who will be empowered to monitor their symptoms and seek early clinical follow-up when recurrence is suspected. This change to a patient-centred model of care may have effects on both quality of life and fear of cancer recurrence. Trial registration: ISRCTN: 13,709,798; 15-Oct-2021. [ABSTRACT FROM AUTHOR]

Background: Solving complex research challenges requires innovative thinking and alternative approaches to traditional methods. One such example is the problem of arm and hand, or upper limb function in multiple sclerosis (MS), a neurological condition affecting approximately 2.9 million people worldwide and more than 150,000 in the United Kingdom. Historically, clinical trials and research have focused on mobility and walking ability. This excludes a large number of patients who are wheelchair users, limiting their quality of life and restricting access to possibly helpful medications. To address this issue, the ThinkHand campaign was launched in 2016, aiming to raise awareness about the importance of upper limb function in MS and develop alternative ways to measure, record, and account for hand and arm function changes. Main body: The campaign utilised innovative strategies at scientific conferences and online surveys to engage people affected by MS, healthcare professionals, charities, and researchers in discussing the importance of preserving upper limb function. Through co-design and interdisciplinary collaboration, the campaign developed new tools like the low-cost cardboard version of the Nine-Hole Peg Test, facilitating remote monitoring of hand function. Additionally, the campaign co-created the "Under & Over" rehabilitation tool, allowing individuals with advanced MS to participate in a remote rehabilitation program. The impact of the ThinkHand campaign has been significant, helping to shift the focus of both academic and industry-supported trials, including the O'HAND and ChariotMS trials, both using upper limb function as their primary end point. The campaign's patient-centred approach highlighted the importance of recognising patients' perspectives in research and challenged established assumptions and practices. It demonstrated the effectiveness of interdisciplinary collaboration, systems thinking, and co-creation with stakeholders in tackling complex problems. Conclusion: The ThinkHand campaign provides valuable insights for health research practices. By involving patients at all stages, researchers can gain a deeper understanding of the impact of disease on their lives, identify gaps and focus research on their needs. Experimentation and iteration can lead to innovative solutions, and openness to unconventional methods can drive widespread change. The ThinkHand campaign exemplifies the potential of patient-centred approaches to address complex research challenges and revolutionise the field of MS research and management. Embracing such approaches will contribute to more inclusive and impactful research in the future. Plain English Summary: Solving complex research challenges requires creative thinking and new ways of doing things. One such challenge is understanding the problems with arm and hand function in multiple sclerosis (MS), a neurological condition that affects more than 150,000 in the United Kingdom. In the past, research focused mainly on walking ability, leaving out many people who use wheelchairs. To tackle this issue, we created the ThinkHand campaign in 2016. Its goal was to raise awareness about the importance of hand and arm function for people with MS (pwMS) and find better ways to measure changes in these functions such that they can become outcomes in clinical trials. This could provide a pathway to better treatments for pwMS who cannot walk. The campaign used various methods, including surveys, social media posts, exhibitions and music to involve pwMS, healthcare professionals, charities, and researchers in discussions about the issues. Working together, they created tools to support pwMS, particularly those at an advanced stage of the disease (pwAMS), to take part in research and measure their hand and arm function. Through our collaborative approach focusing on patients' perspectives, the campaign challenged old ideas and deeply embedded practices. It showed that collaboration between different areas of expertise involving pwMS at all stages of research can help solve complex problems. This campaign teaches us valuable lessons for health research. When researchers listen to patients and try new things, they can better understand how a disease affects people's lives and develop better solutions. In conclusion, we show how embracing a patient-centred approach can address complex research challenges and improve how we study and manage MS and other conditions in the future. [ABSTRACT FROM AUTHOR]

Background: Providing informed consent for trials requires providing trial participants with comprehensive information about the trial, including information about potential risks and benefits. It is required by the ethical principle of respecting patient autonomy. Our study examines the variation in the way information about potential trial benefits and harms is shared in participant information leaflets (PILs). Methods: A total of 214 PILs and informed consent forms from clinical trials units (CTUs) and Clinical Research Facilities (CRFs) in Ireland and the UK were assessed by two authors independently, to check the extent to which they adhered to seven recently developed principles. Discrepancies were resolved by a third. Results: Usage of the seven principles varied widely between PILs regardless of the intended recipient or trial type. None of the PILs used more than four principles, and some (4%) used none. Twenty-seven per cent of PILs presented information about all known potential harms, whereas 45% presented information on all known potential benefits. Some PILs did not provide any potential harms or potential benefits (8%). There was variation in the information contained in adult and children PILs and across disease areas. Conclusion: Significant variation exists in how potential trial benefits and harms are described to potential trial participants in PILs in our sample. Usage of the seven principles of good practice will promote consistency, ensure informed ethical decision-making and invoke trust and transparency. In the long term, a standardised PIL template is needed. [ABSTRACT FROM AUTHOR]

The use of routinely collected electronic healthcare records (EHR) for outcome assessment in clinical trials has been described as a 'disruptive' new technique more than a decade ago. Despite this potential, significant methodological issues and regulatory barriers have hampered the progress in this area. This article discusses the key considerations that trialists should take into account when incorporating EHR into their trials. These include considerations of the clinical relevance of the outcome, data timeliness and quality, ethical and regulatory issues, and some practical considerations for clinical trials units. In addition, this article describes the benefits of using EHR which include cost, reduced trial burden for participants and staff, follow up efficiencies, and improved health economic evaluation procedures. We also describe the major regulatory and start up costs of using EHR in clinical trials. This article focuses on the UK specific EHR landscape in clinical trials and would help researchers and trials units considering the use of this method of outcome data collection in their next trial. If the issues described are mitigated, this method will be a formidable tool for conducting pragmatic clinical trials. [ABSTRACT FROM AUTHOR]

The UK neurosurgical community has a track record of delivering high-quality, practice-changing clinical research studies, facilitated by a robust clinical research infrastructure and close collaborations between neurosurgical centers. More recently, these large-scale studies have been conceived, developed, and delivered by neurosurgical trainees, working under the umbrella of the British Neurosurgical Trainee Research Collaborative (BNTRC). In this paper, we outline the current landscape of large-scale neurosurgical studies in the UK, focusing on the role of trainees in facilitating this research. Importantly, we focus on our experience of trainee-led studies, including the development of the network, current challenges, and future directions. We believe that a similar model can be applied in different settings and countries, which will drive up the quality of neurosurgical research, ultimately benefiting future neurosurgical patients. [ABSTRACT FROM AUTHOR]

All dental practitioners must be proficient at taking a medical history, examining a clothed patient and recognising relevant clinical signs. The general examination of a patient should take into account findings from the history. This paper does not attempt to address the detailed oral and dental examination carried out by dental practitioners but focuses on the holistic patient assessment - essential for safe patient management. [ABSTRACT FROM AUTHOR]

Research applying rational-emotive behavior therapy (REBT) with athletes is sparse and findings are equivocal. REBT can be applied using education workshops, but previous studies in sport have not assessed changes in irrational beliefs following REBT. This paper reports the effects of a single REBT education workshop on irrational beliefs in elite soccer academy athletes from pretest to posttest. Statistical analyses indicate temporary reductions in irrational beliefs following the workshop. Results are discussed with reference to mechanisms of change, study limitations, workshop reflections, and recommendations for developing REBT workshops. [ABSTRACT FROM AUTHOR]

NHS research governance makes it almost impossible to collect certain kinds of data on the everyday life of hospitals and the experience of patients. Fortunately, those of us who get sick enough to be admitted can write about the experience without fear of regulation. This paper presents some observations on clinical ethics, ward organization and infection control that would have been difficult to obtain in any other way, but which illustrate the policy and information costs of the present system. While not personally recommending this as a research strategy, the paper identifies a growing evidence gap and comments on its implications for the delivery of humane and well-organized care. [ABSTRACT FROM AUTHOR]

Abstract: Aim: The Association of Coloproctology of Great Britain and Ireland (ACPGBI) Delphi process identified prevention and treatment of parastomal hernia (PSH) as the second highest priority non‐cancer related colorectal pathology. This position statement aims to summarize the current evidence base. Methods: Four broad themes were identified (prevention, diagnosis/classification, management and operative repair). Guidelines are based on evidence from an extensive literature review using organized searches on the PubMed, MEDLINE, Embase and Cochrane databases. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was adhered to for classifying the quality of evidence and reporting the strength of recommendations. Results: The suture repair of PSH other than for patients in extremis is not recommended. Synthetic non‐absorbable mesh can be used safely in the short term in the construction of colostomies post rectal surgery, but longer‐term follow‐up is needed. Other broad recommendations are made around access to stoma care nurses, prevention classification and management. Conclusion: There is a lack of high quality evidence for many domains in the prevention and treatment of PSH but the results of several studies are awaited. What does this paper add to the literature?: Parastomal hernias are a common and debilitating condition following stoma formation. This position statement from ACPGBI details the current evidence base and ongoing research for the prevention, diagnosis and management of parastomal hernias. [ABSTRACT FROM AUTHOR]

Background: It is crucial to include a wide range of the population in clinical trials for the outcome to be applicable in real-world settings. Existing literature indicates that under-served groups, including disabled people, have been excluded from participating in clinical trials without justification. Exclusion from clinical trials exacerbates disparities in healthcare and diminishes the benefits for excluded populations. Therefore, this study was conducted to investigate potential obstacles that prevent disabled people from participating in clinical trials in the United Kingdom (UK). Methods: The study was carried out through an explanatory sequential mixed methods design. The Imperial Clinical Trials Unit devised and implemented an online questionnaire-based survey (with open/closed-ended questions) and an online focus group discussion. The target population were disabled people, family members/carers of disabled people and staff involved in clinical trials, whereupon the sample was recruited by convenience sampling methods via posters and emails through various networks. The Qualtrics XM survey system was used as the host platform for the online survey, and Microsoft Teams was used for an online focus group discussion. The focus group discussion was conducted to gain a deeper understanding of the themes identified from the survey responses. We analysed responses to the survey via descriptive analysis and used thematic analysis to synthesise the free-text answers from the survey and focus group discussion. Results: We received 45 responses to the survey questionnaire and 5 disabled people took part in a focus group discussion. Our findings highlighted the differences between the perspectives of researchers and those "being researched" and different types of barriers experienced by disabled people: opportunity barriers (inadequate recruitment strategy and ambiguous eligibility criteria), awareness barriers (perception of disability) and acceptance/refusal barriers (available support and adjustment, and sharing of trial results). Conclusion: Our findings support perspectives drawn from the Ford Framework regarding the need to consider all barriers, not just up to the point of enrolment into trials but also beyond the point of inclusion in clinical trials. We support calls for the introduction of legislation on including disabled people in clinical trials, implementation of industry/community-wide participatory approaches and the development of guidelines, a combined public–private approach. [ABSTRACT FROM AUTHOR]

Background: Explainer animations are a means to communicate aspects of clinical trials to participants in a more engaging and accessible way. Delivered well these have the potential to enhance recruitment and retention. The range of media technology used to deliver this material is expanding rapidly but is highly fragmented. Usage of explainer animations across the UK is unknown, the aim of this research was to determine current usage across the 52 registered UK Clinical Research Collaboration (UKCRC) Clinical Trials Units (CTUs) to understand the current landscape and any barriers that could be preventing wider uptake of this functionality. Methods: A survey link was emailed to all UKCRC CTU Directors and Trial Management Leads to ascertain current usage of explainer animations within their CTU. The survey ran between 01 February 2023 and 07 March 2023. Results: Responses were received from 35 CTUs—representing a response rate of 67%. 24 CTUs (69%) reported that they had created/used at least one explainer animation within their unit, although the usage, cost, length and production activities varied among the units. Conclusions: The survey showed that a high proportion of the UKCRC CTUs have used explainer animations to provide information to participants about clinical studies. For those not using the technology yet, the most common reasons cited were a lack of expertise, lack of resources and costs to produce them. One of the desired outcomes of this project is the creation of a free-to-use library of animations to encourage wider uptake and avoid duplication. [ABSTRACT FROM AUTHOR]

Background: Despite the importance of statistical and numerical aspects in key decisions related to clinical trials and their impact in patient's care, patient and public involvement remains underdeveloped in this field. Communication is a barrier to enable successful involvement of patients and the public in numerical aspects. Treatment important differences, a crucial numerical aspect in trials, is considered a priority for patient and public involvement. Creative methods have been proposed to improve communication of technical concepts with members of the public; and to democratise and improve inclusivity in patient and public involvement in health research. Methods: Working with creative professionals, public partners, and statisticians, we aimed to develop, pilot and implement creative workshops to promote a shared understanding of treatment important differences; and co-develop creative prototypes that could be used to communicate the statistical concept to a wider audience in the future. Three 2 to 4 h creative workshops based in the UK were delivered. The first two workshops included 22 participants. They were online and worked as pilots to refine the final in-person workshop via participant feedback and discussion. The final workshop focused on treatment important differences, and we collected information from participants on expectations, subjective numeracy, and experience. Results: The final workshop included 13 participants (5 creative professionals, 4 public partners, and 4 clinical trial statisticians). Participants reported creative workshops helped improve communication of treatment important differences between stakeholders reaching a common understanding of their meaning; and helped democratise knowledge exchange. Each group developed a creative prototype to communicate about treatment important differences with a wider audience, including a song, game, and a cartoon. Participants recommended the format to improve communication of other statistical or complex concepts between stakeholders. Conclusions: Creative workshops can promote shared understanding of complex, statistical concepts and co-development of creative outputs amongst stakeholders. Future work should explore generalisability of the intervention, and what outcomes might be important to consider when implementing creative workshops in patient and public involvement practice. Plain English summary: Patient and public involvement in clinical trials helps improve their relevance. Decisions related to numbers in trials consider information related to patients and their clinical experience, but patients and the public are rarely involved in these decisions. One barrier to achieve this is communication: numbers can be challenging to discuss. Creative methods (including writing, dancing, drawing) have been suggested as a potential way to improve communication of numbers with a wide audience. Working with creative professionals, public partners, and statisticians we developed, piloted, and implemented a creative workshop focusing on improving communication by reaching a common understanding between participants of a specific numerical concept related to clinical trials and where patient and public involvement is crucial. The creative workshop aimed to facilitate mutual learning between creative professionals, members of the public, and statisticians; and to promote co-development of creative outputs to describe the same numerical concept to a wider audience. Workshop participants felt the creative workshops improved communication of the numerical concept and helped everyone feel heard. Workshop participants were particularly interested in visual methods to support communication, and recommended creative workshops should be used to improve communication of other statistical and complex concepts. [ABSTRACT FROM AUTHOR]

Introduction: Increased moderate to vigorous physical activity (MVPA) can improve clinical and psychosocial outcomes for people living with and beyond cancer (LWBC). This study aimed to assess the feasibility and acceptability of trial procedures in a pilot randomised controlled trial (RCT) of a theory‐driven app‐based intervention with behavioural support focused on promoting brisk walking (a form of MVPA) in people LWBC (APPROACH). Methods: Participants diagnosed with breast, prostate or colorectal cancer were recruited from a single UK hospital site. Assessments at baseline and 3 months included online questionnaires, device‐measured brisk walking (activPAL accelerometer) and self‐reported weight and height. Participants were randomised to intervention or control (care as usual). The intervention comprised a non‐cancer‐specific app to promote brisk walking (National Health Service 'Active 10') augmented with print information about habit formation, a walking planner and two behavioural support telephone calls. Feasibility and acceptability of trial procedures were explored. Initial estimates for physical activity informed a power calculation for a phase III RCT. A preliminary health economics analysis was conducted. Results: Of those medically eligible, 369/577 (64%) were willing to answer further eligibility questions and 90/148 (61%) of those eligible were enrolled. Feasibility outcomes, including retention (97%), assessment completion rates (>86%) and app download rates in the intervention group (96%), suggest that the trial procedures are acceptable and that the intervention is feasible. The phase III RCT will require 472 participants to be randomised. As expected, the preliminary health economic analyses indicate a high level of uncertainty around the cost‐effectiveness of the intervention. Conclusions: This pilot study demonstrates that a large trial of the brisk walking intervention with behavioural support is both feasible and acceptable to people LWBC. The results support progression onto a confirmatory phase III trial to determine the efficacy and cost‐effectiveness of the intervention. [ABSTRACT FROM AUTHOR]

In 1796, American physician Elisha Perkins patented "metallick Tractors" for the treatment of various ailments, particularly those associated with pain. They were subsequently rapidly and widely disseminated in the United States and Great Britain based on testimonials and deceptive marketing tactics. Dissemination was facilitated by endorsements from prominent physicians, politicians, and clergymen; quasi-theoretical, handwaving explanations of efficacy based on Galvani's then-current experiments; and the procedure's apparent safety and simplicity. However, blinded placebo-controlled trials in Great Britain using sham devices demonstrated that the therapy was ineffective. In response, in the period from 1798 to 1806, Perkinists unleashed a barrage of disinformation (ad hominem attacks, misleading arguments, unethical propaganda tactics, and poetic and graphic satire) to sway public opinion in favor of the fraudulent therapy and against its critics. The disinformation slowed the abandonment of "tractoration", but higher-level scientific argumentation ultimately prevailed. The Perkinist disinformation campaign had antecedents with the Mesmerist disinformation campaign in the mid-1780s. Similar propaganda tactics are still widely employed to encourage the purchase and use of disproven or fraudulent therapies, as evidenced by propaganda from adherents of acupuncture in response to negative clinical trials and from supporters of unsafe and ineffective therapies promulgated during COVID-19. [ABSTRACT FROM AUTHOR]

Background: Statisticians are fundamental in ensuring clinical research, including clinical trials, are conducted with quality, transparency, reproducibility and integrity. Good Clinical Practice (GCP) is an international quality standard for the conduct of clinical trials research. Statisticians are required to undertake training on GCP but existing training is generic and, crucially, does not cover statistical activities. This results in statisticians undertaking training mostly unrelated to their role and variation in awareness and implementation of relevant regulatory requirements with regards to statistical conduct. The need for role-relevant training is recognised by the UK NHS Health Research Authority and the Medicines and Healthcare products Regulatory Agency (MHRA). Methods: The Good Statistical Practice (GCP for Statisticians) project was instigated by the UK Clinical Research Collaboration (UKCRC) Registered Clinical Trials Unit (CTU) Statisticians Operational Group and funded by the National Institute for Health and Care Research (NIHR), to develop materials to enable role-specific GCP training tailored to statisticians. Review of current GCP training was undertaken by survey. Development of training materials were based on MHRA GCP. Critical review and piloting was conducted with UKCRC CTU and NIHR researchers with comment from MHRA. Final review was conducted through the UKCRC CTU Statistics group. Results: The survey confirmed the need and desire for the development of dedicated GCP training for statisticians. An accessible, comprehensive, piloted training package was developed tailored to statisticians working in clinical research, particularly the clinical trials arena. The training materials cover legislation and guidance for best practice across all clinical trial processes with statistical involvement, including exercises and real-life scenarios to bridge the gap between theory and practice. Comprehensive feedback was incorporated. The training materials are freely available for national and international adoption. Conclusion: All research staff should have training in GCP yet the training undertaken by most academic statisticians does not cover activities related to their role. The Good Statistical Practice (GCP for Statisticians) project has developed and extensively piloted new, role-specific, comprehensive, accessible GCP training tailored to statisticians working in clinical research, particularly the clinical trials arena. This role-specific training will encourage best practice, leading to transparent and reproducible statistical activity, as required by regulatory authorities and funders. [ABSTRACT FROM AUTHOR]

Interleukin (IL)-17A and IL-17F have overlapping roles in pro-inflammatory signaling and have been implicated in the pathogenesis of psoriatic disease. Bimekizumab is the first human monoclonal antibody to selectively inhibit IL-17F in addition to IL-17A. Bimekizumab has been studied in several phase II/III trials and has been approved for the treatment of patients with psoriatic arthritis (PsA) in the EU and UK. A literature search identified clinical trials examining the efficacy and safety of bimekizumab for PsA, which were critically appraised. Clinical trials of bimekizumab in PsA have demonstrated rapid and sustained treatment responses and depth of response across the multiple disease domains. High levels of efficacy were sustained to 152 weeks in phase IIb trials, and to 52 weeks in phase III trials. Bimekizumab was generally well tolerated. As expected, due to the role of IL-17 in the immune response to fungal pathogens, there was an increase in mild-to-moderate, localized fungal infections with bimekizumab treatment, very few of which led to discontinuation. Studies over longer time periods, with relevant comparators from the IL-17A inhibitor class, and real-world data will be important to further define the role of bimekizumab among currently available treatments for PsA. [ABSTRACT FROM AUTHOR]

Previous application of value-of-information methods to optimal clinical trial design have predominantly taken a societal decision-making perspective, implicitly assuming that healthcare costs are covered through public expenditure and trial research is funded by government or donation-based philanthropic agencies. In this paper, we consider the interaction between interrelated perspectives of a societal decision maker (e.g. the National Institute for Health and Clinical Excellence [NICE] in the UK) charged with the responsibility for approving new health interventions for reimbursement and the company that holds the patent for a new intervention. We establish optimal decision making from societal and company perspectives, allowing for trade-offs between the value and cost of research and the price of the new intervention. Given the current level of evidence, there exists a maximum (threshold) price acceptable to the decision maker. Submission for approval with prices above this threshold will be refused. Given the current level of evidence and the decision maker's threshold price, there exists a minimum (threshold) price acceptable to the company. If the decision maker's threshold price exceeds the company's, then current evidence is sufficient since any price between the thresholds is acceptable to both. On the other hand, if the decision maker's threshold price is lower than the company's, then no price is acceptable to both and the company's optimal strategy is to commission additional research. The methods are illustrated using a recent example from the literature. [ABSTRACT FROM AUTHOR]

Background: In healthcare research the randomised controlled trial is seen as the gold standard because it ensures selection bias is minimised. However, there is uncertainty as to which is the most preferred method of randomisation in any given setting and to what extent more complex methods are actually being implemented in the field. Methods: In this paper we describe the results of a survey of UK academics and publicly funded researchers to examine the extent of the use of various methods of randomisation in clinical trials. Results: Trialists reported using simple randomisation, permuted blocks and stratification more often than more complex methods such as minimisation. Most trialists believed that simple randomisation is suitable for larger trials but there is a high probability of possible imbalance between treatment groups in small trials. It was thought that groups should be balanced at baseline to avoid imbalance and help face-validity. However, very few respondents considered that more complex methods offer any advantages. Conclusions: This paper demonstrates that for most UK trialists the preferred method of randomisation is using permuted blocks of varying random length within strata. This method eliminates the problem of predictability while maintaining balance across combinations of factors. If the number of prognostic factors is large, then minimisation can be used to provide treatment balance as well as balance over these factors. However, only those factors known to affect outcome should be considered. [ABSTRACT FROM AUTHOR]