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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]

Background: Sharing trial results with participants is a moral imperative, but too often does not happen in appropriate ways. Methods: We carried out semi-structured interviews with patients (n = 13) and site staff (n = 11), and surveyed 180 patients and 68 site staff who were part of the Show RESPECT study, which tested approaches to sharing results with participants in the context of the ICON8 ovarian cancer trial (ISRCTN10356387). Qualitative and free-text data were analysed thematically, and findings used to develop the SHOW RESPECT adaptable framework of considerations for planning how to share trial results with participants. This paper presents the framework, with illustrations drawn from the Show RESPECT study. Results: Our adaptable 'SHOW RESPECT' framework covers (1) Supporting and preparing trial participants to receive results, (2) HOw will the results reach participants?, (3) Who are the trial participants?, (4) REsults—what do they show?, (5) Special considerations, (6) Provider—who will share results with participants?, (7) Expertise and resources, (8) Communication tools and (9) Timing of sharing results. While the data upon which the framework is based come from a single trial, many of our findings are corroborated by findings from other studies in this area, supporting the transferability of our framework to trials beyond the UK ovarian cancer setting in which our work took place. Conclusions: This adaptable 'SHOW RESPECT' framework can guide researchers as they plan how to share aggregate trial results with participants. While our data are drawn from a single trial context, the findings from Show RESPECT illustrate how approaches to communication in a specific trial can influence patient and staff experiences of feedback of trial results. The framework generated from these findings can be adapted to fit different trial contexts and used by other researchers to plan the sharing of results with their own participants. Trial registration: ISRCTN96189403. Registered on February 26, 2019. Show RESPECT was supported by the Medical Research Council (MC_UU_12023/24 and MC_UU_00004/08) and the NIHR CRN. [ABSTRACT FROM AUTHOR]

Objectives: To establish if Black adults and adult ethnic minorities, defined as any group except White British, were represented in UK-based COVID-19 vaccination randomised controlled trials (RCTs) when compared to corresponding UK population proportions, based on 2011 census data. Design: Systematic review of COVID-19 Randomised Controlled Vaccine Trials Setting: United Kingdom Participants: Randomised Controlled Trials of COVID-19 vaccines conducted in the UK were systematically reviewed following PRISMA guidelines. MeSH terms included "Covid-19 vaccine", "Ad26COVS1", and "BNT162 Vaccine" with keywords such as [covishield OR coronavac OR Vaxzevria OR NVX-CoV2373] also used. Studies that provided (A) participant demographics and (B) full eligibility criteria were included. The following key data was extracted for analysis: number of participants analysed, number of Black adults and number of adult minority ethnicity participants. Primary and Secondary Outcome Measures: The primary outcome is the mean percentage of Black adults randomised to COVID-19 vaccine trials deemed eligible within this review. The secondary outcome is the mean percentage of adult ethnic minorities randomised. Results: The final review included 7 papers and a total of 87 sets of data collated from trial sites across the UK. The standard mean percentage of Black adults included in the trials (0.59%, 95% CI: 0.13% - 1.05%) was significantly lower compared to the recorded Black adult population (2.67%) indicating that they were under-served in UK based COVID-19 vaccine RCTs (p < 0.001). Adult ethnic minority presence (8.94%, 95% CI: 2.07% - 15.80%) was also lower than census data (16.30%), indicating they were also under-served (p = 0.039). Conclusion: The findings show that COVID-19 vaccine trials failed to adequately randomise proportionate numbers of Black adults and adult minority ethnicities. More inclusive practices must be developed and implemented in the recruitment of underserved groups to understand the true impact of COVID-19. [ABSTRACT FROM AUTHOR]

Background: In early 2021, the Department of Health and Social Care in the UK called for research on the safety and immunogenicity of concomitant administration of COVID-19 and influenza vaccines. Co-administration of these vaccines would facilitate uptake and reduce the number of healthcare visits required. The ComFluCOV trial was designed to deliver the necessary evidence in time to inform the autumn (September–November) 2021 vaccination policy. This paper presents the statistical methodology applied to help successfully deliver the trial results in 6 months. Methods: ComFluCOV was a parallel-group multicentre randomised controlled trial managed by the Bristol Trials Centre. Two study statisticians, supported by a senior statistician, worked together on all statistical tasks. Tools were developed to aid the pre-screening process. Automated data monitoring reports of clinic data and electronic diaries were produced daily and reviewed by the trial team and feedback provided to sites. Analyses were performed independently in parallel, and derivations and results of all outcomes were compared. Results: Set-up was achieved in less than a month, and 679 participants were recruited over 8 weeks. A total of 537 [at least] daily reports outlining recruitment, protocol adherence, and data quality, and 695 daily reports of participant electronic diaries identifying any missed diary entries and adverse events were produced over a period of 16 weeks. A preliminary primary outcome analysis of validated data was reported to the Department of Health and Social Care in May 2021. The database was locked 6 weeks after the final participant follow-up and final analyses completed 3 weeks later. A pre-print publication was submitted within 14 days of the results being made available. The results were reported 6 months after first discussions about the trial. Conclusion: The statistical methodologies implemented in ComFluCOV helped to deliver the study in the timescale set. Working in a new clinical area to tight timescales was challenging. Having two statisticians working together on the study provided a quality assurance process that enabled analyses to be completed efficiently and ensured data were interpreted correctly. Processes developed could be applied to other studies to maximise quality, reduce the risk of errors, and overall provide enhanced validation methods. Trial registration: ISRCTN14391248, registered on 30 March 2021 [ABSTRACT FROM AUTHOR]

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

Background: Social jetlag is a chronic disruption of sleep timing that is characterized by different sleep timing during workdays and free days. Social jetlag has been associated with disturbed glucose metabolism, insulin resistance, and increased risk of metabolic syndrome and type 2 diabetes. In this study, we aim to investigate whether a combination of bright light therapy in the morning, bright light reduction in the evening and sleep advance instructions for 3 weeks reduces social jetlag and if this results in improvement of glycemic and metabolic control, sleep, mood and quality of life after 3 and 12 weeks in people with prediabetes and type 2 diabetes and to assess possible mediators, compared to regular sleep habits. Methods: In this randomized controlled trial, 60 people with prediabetes or type 2 diabetes with > 1 h social jetlag will be recruited. The intervention consists of bright light therapy (5000 lx) emitted by Vitamine-L (Lumie, UK) for 30 min each morning, combined with the advice to follow sleep advance instructions and to wear bright light-dimming goggles every evening for a period of 3 weeks. The control group adheres to their regular sleep habits and conditions. The primary outcome is glycated hemoglobin (HbA1c) after 12 weeks comparing the intervention and control in an intention-to-treat analysis. Secondary outcomes at 3 and 12 weeks are (1) social jetlag; (2) insulin sensitivity, fasting blood glucose, glucose-lowering medication use, and frequency of perceived hypoglycemia; (3) metabolic outcomes, including body mass index (BMI), waist circumference, body fat percentage, and blood pressure; (4) mood, including depression, fatigue and anxiety (measured with questionnaires); and (5) quality of life measured using EQ5D questionnaire. To assess other factors that might play a role as possible mediators, we will measure (para)sympathetic nervous system activity assessed with ECGs and electrochemical skin conductance tests, sleep quality and sleep phase distribution assessed with a sleep measuring headband (ZMax), the Dim Light Melatonin Onset in saliva samples (in a subgroup) at 3 and 12 weeks, the feeling of satiety and satiation with a 10-cm visual analog scale (VAS), diet using a food frequency questionnaire, and physical activity using an accelerometer (ActiGraph). Discussion: Social jetlag can contribute to poorer glycemic control and metabolic control in those with type 2 diabetes. With this intervention, we aim to reduce social jetlag and thereby improve glycemic and metabolic control. This could offer a way to improve overall population health and to reduce the disease burden of type 2 diabetes. Trial registration: ISRCTN registry ISRCTN11967109. Registered on 9 May 2024. [ABSTRACT FROM AUTHOR]

Background: People with serious mental health problems (SMHP) are more likely to be admitted to psychiatric hospital following contact with crisis services. Admissions can have significant personal costs, be traumatic and are the most expensive form of mental health care. There is an urgent need for treatments to reduce suicidal thoughts and behaviours and reduce avoidable psychiatric admissions. Methods: A multi-stage, multi-arm (MAMS) randomised controlled trial (RCT) with four arms conducted over two stages to determine the clinical and cost effectiveness of three psychosocial treatments, compared to treatment as usual (TAU), for people with SMHP who have had recent suicidal crisis. Primary outcome is any psychiatric hospital admissions over a 6-month period. We will assess the impact on suicidal thoughts and behaviour, hope, recovery, anxiety and depression. The remote treatments delivered over 3 months are structured peer support (PREVAIL); a safety planning approach (SAFETEL) delivered by assistant psychologists; and a CBT-based suicide prevention app accessed via a smartphone (BrighterSide). Recruitment is at five UK sites. Stage 1 includes an internal pilot with a priori progression criteria. In stage 1, the randomisation ratio was 1:1:1:2 in favour of TAU. This has been amended to 2:2:3 in favour of TAU following an unplanned change to remove the BrighterSide arm following the release of efficacy data from an independent RCT. Randomisation is via an independent remote web-based randomisation system using randomly permuted blocks, stratified by site. An interim analysis will be performed using data from the first 385 participants from PREVAIL, SAFETEL and TAU with outcome data at 6 months. If one arm is dropped for lack of benefit in stage 2, the allocation ratio of future participants will be 1:1. The expected total sample size is 1064 participants (1118 inclusive of BrighterSide participants). Discussion: There is a need for evidence-based interventions to reduce psychiatric admissions, via reduction of suicidality. Our focus on remote delivery of established brief psychosocial interventions, utilisation of different modalities of delivery that can provide sustainable and scalable solutions, which are also suitable for a pandemic or national crisis context, will significantly advance treatment options. Trial registration: ISRCTN33079589. Registered on June 20, 2022. [ABSTRACT FROM AUTHOR]

Background: Liver disease is the third leading cause of premature death in the UK. Transplantation is the only successful treatment for end-stage liver disease but is limited by a shortage of suitable donor organs. As a result, up to 20% of patients on liver transplant waiting lists die before receiving a transplant. A third of donated livers are not suitable for transplant, often due to steatosis. Hepatic steatosis, which affects 33% of the UK population, is strongly associated with obesity, an increasing problem in the potential donor pool. We have recently tested defatting interventions during normothermic machine perfusion (NMP) in discarded steatotic human livers that were not transplanted. A combination of therapies including forskolin (NKH477) and L-carnitine to defat liver cells and lipoprotein apheresis filtration were investigated. These interventions resulted in functional improvement during perfusion and reduced the intrahepatocellular triglyceride (IHTG) content. We hypothesise that defatting during NMP will allow more steatotic livers to be transplanted with improved outcomes. Methods: In the proposed multi-centre clinical trial, we will randomly assign 60 livers from donors with a high-risk of hepatic steatosis to either NMP alone or NMP with defatting interventions. We aim to test the safety and feasibility of the defatting intervention and will explore efficacy by comparing ex-situ and post-reperfusion liver function between the groups. The primary endpoint will be the proportion of livers that achieve predefined functional criteria during perfusion which indicate potential suitability for transplantation. These criteria reflect hepatic metabolism and injury and include lactate clearance, perfusate pH, glucose metabolism, bile composition, vascular flows and transaminase levels. Clinical secondary endpoints will include proportion of livers transplanted in the two arms, graft function; cell-free DNA (cfDNA) at follow-up visits; patient and graft survival; hospital and ITU stay; evidence of ischemia-reperfusion injury (IRI); non-anastomotic biliary strictures and recurrence of steatosis (determined on MRI at 6 months). Discussion: This study explores ex-situ pharmacological optimisation of steatotic donor livers during NMP. If the intervention proves effective, it will allow the safe transplantation of livers that are currently very likely to be discarded, thereby reducing waiting list deaths. Trial registration: ISRCTN ISRCTN14957538. Registered in October 2022. [ABSTRACT FROM AUTHOR]

Background: Patients from socioeconomically disadvantaged backgrounds are underserved in randomised controlled trials, yet they experience a much greater burden of disease compared with patients from socioeconomically advantaged areas. It is crucial to make trials more inclusive to ensure that treatments and interventions are safe and effective in real-world contexts. Improving how information about trials is verbally communicated is an unexplored strategy to make trials more inclusive. This study examined how trials are communicated verbally, comparing consultations involving patients from the most and least socioeconomically disadvantaged areas. Methods: Secondary qualitative analysis of 55 trial consultation transcripts from 41 patients, sampled from 3 qualitative studies embedded in their respective UK multi-site, cancer-related randomised controlled trials. Patients living in the most and least socioeconomically disadvantaged areas, defined using English Indices of Multiple Deprivation decile scores, were purposively sampled. Analysis was largely thematic and drew on the constant comparison method. Results: Recruiters communicated clinical uncertainty in a similar way for patients living in different socioeconomic areas. Consultations with disadvantaged patients were, on average, half the duration of those with advantaged patients, and tended to involve recruiters providing less in-depth explanations of trial concepts, used phrasing that softened trial arm risks, and described trial processes (e.g. randomisation) using informal or metaphorical phrasing. Disadvantaged and advantaged patients differed in the concerns they expressed; disadvantaged patients voiced fewer concerns and asked fewer questions but were also less likely to be invited to do so by recruiters. Conclusion: Interactions about trials unfolded in different ways between patients living in different socioeconomic areas, likely due to both patient- and recruiter-related factors. We present considerations for recruiters when discussing trials with patients from socioeconomically disadvantaged backgrounds, aimed at enhancing trial communication. Future research should examine disadvantaged patients' and recruiters' experiences of verbal trial communication to inform guidance that addresses the needs and preferences of underserved groups. [ABSTRACT FROM AUTHOR]

Background: Retaining participants in randomised controlled trials (RCTs) is challenging and trial teams are often required to use strategies to ensure retention or improve it. Other than monetary incentives, there is no requirement to disclose the use of retention strategies to the participant. Additionally, not all retention strategies are developed at the planning stage, i.e. post-funding during protocol development, but some protocols include strategies for participant retention as retention is considered and planned for early in the trial planning stage. It is yet unknown if these plans are communicated in the corresponding participant information leaflets (PILs). The purpose of our study was to determine if PILs communicate plans to promote participant retention and, if so, are these outlined in the corresponding trial protocol. Methods: Ninety-two adult PILs and their 90 corresponding protocols from Clinical Trial Units (CTUs) in the UK were analysed. Directed (deductive) content analysis was used to analyse the participant retention text from the PILs. Data were presented using a narrative summary and frequencies where appropriate. Results: Plans to promote participant retention were communicated in 81.5% (n = 75/92) of PILs. Fifty-seven percent (n = 43/75) of PILs communicated plans to use "combined strategies" to promote participant retention. The most common individual retention strategy was telling the participants that data collection for the trial would be scheduled during routine care visits (16%; n = 12/75 PILs). The importance of retention and the impact that missing or deleted data (deleting data collected prior to withdrawal) has on the ability to answer the research question were explained in 6.5% (n = 6/92) and 5.4% (n = 5/92) of PILs respectively. Out of the 59 PILs and 58 matching protocols that both communicated plans to use strategies to promote participant retention, 18.6% (n = 11/59) communicated the same information, the remaining 81.4% (n = 48/59) of PILs either only partially communicated (45.8%; n = 27/59) the same information or did not communicate the same information (35.6%; n = 21/59) as the protocol with regard to the retention strategy(ies). Conclusion: Retention strategies are frequently communicated to potential trial participants in PILs; however, the information provided often differs from the content in the corresponding protocol. Participant retention considerations are best done at the planning stage of the trial and we encourage trial teams to be consistent in the communication of these strategies in both the protocol and PIL. [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]

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: Two million people in the UK are living with or beyond cancer and a third of them report poor quality of life (QoL) due to problems such as fatigue, fear of cancer recurrence, and concerns about returning to work. We aimed to develop and evaluate an intervention based on acceptance and commitment therapy (ACT), suited to address the concerns of cancer survivors and in improving their QoL. We also recognise the importance of exercise and vocational activity on QoL and therefore will integrate options for physical activity and return to work/vocational support, thus ACT Plus (+). Methods: We will conduct a multi-centre, pragmatic, theory driven, randomised controlled trial. We will assess whether ACT+ including usual aftercare (intervention) is more effective and cost-effective than usual aftercare alone (control). The primary outcome is QoL of participants living with or beyond cancer measured using the Functional Assessment of Cancer Therapy: General scale (FACT-G) at 52 weeks. We will recruit 344 participants identified from secondary care sites who have completed hospital-based treatment for cancer with curative intent, with low QoL (determined by the FACT-G) and randomise with an allocation ratio of 1:1 to the intervention or control. The intervention (ACT+) will be delivered by NHS Talking Therapies, specialist services, and cancer charities. The intervention consists of up to eight sessions at weekly or fortnightly intervals using different modalities of delivery to suit individual needs, i.e. face-to-face sessions, over the phone or skype. Discussion: To date, there have been no robust trials reporting both clinical and cost-effectiveness of an ACT based intervention for people with low QoL after curative cancer treatment in the UK. We will provide high quality evidence of the effectiveness and cost-effectiveness of adding ACT+ to usual aftercare provided by the NHS. If shown to be effective and cost-effective then commissioners, providers and cancer charities will know how to improve QoL in cancer survivors and their families. Trial registration: ISRCTN: ISRCTN67900293. Registered on 09 December 2019. All items from the World Health Organization Trial Registration Data Set for this protocol can be found in Additional file 2 Table S1. [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]

Populations around the world are rapidly ageing and more people are living with multiple long-term conditions. There is an urgent need for evidence about high quality, cost-effective, and integrated systems of health and social care. Health research funders are now also prioritising research in adult social care and wider local authority settings, e.g. housing services. Developing the evidence base for adult social care should include implementing randomised controlled trials, where appropriate. Within the UK, the clinical trial is the established road map for evaluating interventions in the National Health Service (NHS). However, adult social care and local authorities are relatively uncharted territory for trials. BATH-OUT-2 is one of the first clinical trials currently underway within adult social care and housing adaptations services in six English local authorities. It provides an opportunity to explore how the clinical trial road map fares in these settings. Whilst setting up BATH-OUT-2, we encountered challenges with securing funding for the trial, lack of non-NHS intervention costs, using research and support costs as intended, gaining approvals, identifying additional trial sites, and including people who lack the mental capacity to provide informed consent. Overall, our experience has been like navigating uncharted territory with a borrowed map. In the UK, the clinical trial road map was developed for medical settings. Its key features are integrated within the NHS landscape but have been largely absent, unfamiliar, inaccessible, or irrelevant in social care and wider local authority terrain. Navigating the set-up of a clinical trial outside the NHS has been a complicated and disorientating journey. BATH-OUT-2 highlights how local authorities generally and adult social care specifically are a relatively new and certainly different type of setting for trials. Whilst this poses a challenge for conducting trials, it also presents an opportunity to question longstanding assumptions within trials practices, reimagine the conventional clinical trial road map, and take it in new directions. As the UK research landscape moves forward and becomes better primed for randomised evaluations in local authorities, we propose several suggestions for building on recent progress and advancing trials within adult social care and across health and care systems. [ABSTRACT FROM AUTHOR]

Background: Without surgical repair, flexor tendon injuries do not heal and patients' ability to bend fingers and grip objects is impaired. However, flexor tendon repair surgery also requires optimal rehabilitation. There are currently three custom-made splints used in the rehabilitation of zone I/II flexor tendon repairs, each with different assumed harm/benefit profiles: the dorsal forearm and hand-based splint (long), the Manchester short splint (short), and the relative motion flexion splint (mini). There is, however, no robust evidence as to which splint, if any, is most clinical or cost effective. The Flexor Injury Rehabilitation Splint Trial (FIRST) was designed to address this evidence gap. Methods: FIRST is a parallel group, superiority, analyst-blind, multi-centre, individual participant-randomised controlled trial. Participants will be assigned 1:1:1 to receive either the long, short, or mini splint. We aim to recruit 429 participants undergoing rehabilitation following zone I/II flexor tendon repair surgery. Potential participants will initially be identified prior to surgery, in NHS hand clinics across the UK, and consented and randomised at their splint fitting appointment post-surgery. The primary outcome will be the mean post-randomisation score on the patient-reported wrist and hand evaluation measure (PRWHE), assessed at 6, 12, 26, and 52 weeks post randomisation. Secondary outcome measures include blinded grip strength and active range of movement (AROM) assessments, adverse events, adherence to the splinting protocol (measured via temperature sensors inserted into the splints), quality of life assessment, and further patient-reported outcomes. An economic evaluation will assess the cost-effectiveness of each splint, and a qualitative sub-study will evaluate participants' preferences for, and experiences of wearing, the splints. Furthermore, a mediation analysis will determine the relationship between patient preferences, splint adherence, and splint effectiveness. Discussion: FIRST will compare the three splints with respect to clinical efficacy, complications, quality of life and cost-effectiveness. FIRST is a pragmatic trial which will recruit from 26 NHS sites to allow findings to be generalisable to current clinical practice in the UK. It will also provide significant insights into patient experiences of splint wear and how adherence to splinting may impact outcomes. Trial registration: ISRCTN: 10236011 [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]

Background: The NIHR's Associate Principal Investigator (API) Scheme in the United Kingdom was expanded nationally in 2020 with the aim of training clinicians to become Principal Investigators for clinical research in the future. The HEAL-COVID adaptive platform trial is an urgent public health study registered with the API Scheme. Within eighteen months of opening, the trial had recruited almost 1200 patients with over 100 active sites. Here we describe our experiences of APIs working on the trial with two broad objectives. Firstly, we aim to explore through qualitative methods the impact that the scheme has had on the APIs' professional development. Secondly, we aim to quantify the impact that the APIs have had on the recruitment of patients into the trial. Methods: The professional backgrounds of the APIs are described from data from their application forms to the scheme. The HEAL-COVID API Network is described from records of the monthly meetings. The APIs' experiences are reviewed from data from the NIHR exit surveys at 6 months and from a reflective practice exercise at the final network meeting. Data of patient recruitment to HEAL-COVID was analysed for centres with and without APIs via a multivariate analysis. Results: Forty-two APIs were registered with the HEAL-COVID trial with a diversity of backgrounds in terms of gender, country, profession, grade and specialty. Eleven monthly network meetings took place with the dual objectives of facilitating trial activity and providing educational content. Fourteen APIs completed the NIHR survey with all reporting Good Clinical Practice completion, local promotional activity of the trial, patient recruitment and support from their respective PI. Sites with at least one API recruited over 3.5 times more patients than sites without an API (medians 4 vs 14.5, p < 0.05), independent of factors including type of hospital or number of inpatient beds. Discussion: This study adds to the growing literature that the NIHR's API Scheme is effective in meeting its objectives in providing research training to clinicians, thus building a workforce of future clinical researchers. Moreover, data from the HEAL-COVID trial shows that sites with an API are associated with higher recruitment. Overall, registering a trial with the API Scheme not only trains future clinical researchers, but it is also likely to increase the number of patients recruited (amongst other benefits), increasing the efficiency of trials and improving access for patients. [ABSTRACT FROM AUTHOR]

Background: In February 2021, the UK Department of Health and Social Care sought evidence on the safety and immunogenicity of COVID-19 and influenza vaccine co-administration to inform the 2021/2022 influenza vaccine policy. Co-administration could support vaccine uptake and reduce healthcare appointments. ComFluCOV was a randomised controlled trial designed to provide this evidence. This report outlines the methods used to deliver the trial in 6 months to answer an urgent public health question as part of the COVID-19 pandemic response. Methods: ComFluCOV was commissioned by the Department of Health and Social Care and was managed by the Bristol Trials Centre, a UK-registered clinical trials unit. It was classed as an Urgent Public Health trial which facilitated fast-track regulatory approvals. Trial materials and databases were developed using in-house templates and those used in other COVID-19 vaccine trials. Participants were recruited by advertising, and via a trial website. Electronic trial systems enabled daily review of participant data. Weekly virtual meetings were held with stakeholders and trial sites. Results: ComFluCOV was delivered within 6 months from inception to reporting, and trial milestones to inform the Department of Health and Social Care policy were met. Set-up was achieved within 1 month. Regulators provided expedited reviews, with feedback ahead of submission. Recruitment took place at 12 sites. Over 380 site staff were trained. Overall, 679 participants were recruited in two months. The final report to the Department of Health and Social Care was submitted in September 2021, following a preliminary safety report in May 2021. Trial results have been published. Conclusion: The rapid delivery of ComFluCOV was resource intensive. It was made possible in part due to a unique set of circumstances created by the pandemic situation including measures put in place to support urgent public health research and public support for COVID-19 vaccine research. Elements of the trial could be adopted to increase efficiency in 'non-pandemic' situations including working with a clinical trials unit to enable immediate mobilisation of a team of experienced researchers, greater sharing of resources between clinical trials units, use of electronic trial systems and virtual meetings. Trial registration: ISRCTN14391248, submitted on 17/03/2021. Registered on 30/03/2021. [ABSTRACT FROM AUTHOR]

Background: There is a pressing need to offer more accessible, evidence-based psychological interventions to secondary school students who are increasingly reporting difficulties with anxiety and low mood. The aim of this pragmatic randomised multiple baseline trial is to evaluate the efficacy of a school-based counselling intervention called Knowledge Insight Tools (KIT) for reducing anxiety and low mood in UK secondary school students. KIT is a flexible intervention delivered individually and informed by cognitive behavioural therapy (CBT)., Methods: We will use a randomised multiple baseline design whereby young people will be randomly allocated to a baseline wait period of 3, 4, 5, 6, 7, or 8 weekly measurements, followed by receiving up to 10 weekly sessions of KIT delivered by trained, school-based practitioners. We aim to recruit 60 young people aged 11-18 who are primarily experiencing problems with low mood and/or anxiety from secondary schools across England and Scotland. We will assess child-reported anxiety, mood, and general psychological distress/coping with the Young Person's Clinical Outcomes in Routine Evaluation (YP-CORE), recorded at each session during the baseline and intervention phases. We will also assess child-reported anxiety and low mood with the Revised Children's Anxiety and Depression Scale (RCADS) at the beginning and end of treatment; practitioner-reported treatment fidelity with the KIT Fidelity Checklist; and practitioner-reported feasibility with an end-of-treatment Implementation Survey. We will analyse within-person and between-person change in YP-CORE scores across the baseline and intervention phases using visual analysis and piecewise multilevel growth curve models. We will also analyse pre-post changes in YP-CORE scores using randomisation tests, and reliable and clinically significant change using the RCADS scores., Discussion: The KIT trial is a pragmatic, randomised multiple baseline trial aimed at evaluating a school-based, individual CBT counselling intervention for reducing anxiety and low mood in UK secondary school students. Results will directly inform the provision of KIT in school-based counselling services, as well as the growing evidence-base for school-based CBT interventions., Trial Registration: ClinicalTrials.gov NCT06188962. Retrospectively registered on 02/01/24., (© 2024. The Author(s).)

Background: Interest in and use of electronic consent (e-consent) in the conduct of academic clinical trials has increased since the COVID-19 pandemic. E-consent offers advantages including increased efficiency and accessibility, and reduced burden on site staff, which can be appealing to academic trialists anticipating challenges in recruitment to complex trial designs or with limited funding. However, there are many options to consider when using e-consent in a study protocol. This paper presents five case studies from Norwich Clinical Trials Unit, demonstrating how e-consent models can be effectively tailored to the needs of different trials. These examples illustrate the options around and benefits of e-consent, the acceptability of e-consent by participants, and the design considerations that were made during the development of the trial protocols., Case Studies: Five randomised trials are presented, selected from a range of different trial designs, disease areas, interventions, and patient populations. E-consent was either offered as an alternative to paper consent, according to participant preference, or as the sole method of consent. E-consent was generally used to facilitate remote consent in decentralised trials but was also chosen to increase efficiency and reduce burden in an emergency department setting. The technical implementation of e-consent and detailed participant procedures were tailored to the needs of the trial settings and patient populations. For example, accompanying participant information sheets were provided in paper or electronic form, and electronic signatures could be typed or drawn. Administrative data on uptake of e-consent is presented where available., Conclusion: This paper demonstrates that the operational and technical aspects of implementing e-consent in clinical trials can be influenced by the trial design, the needs and characteristics of the trial population, financial/efficiency considerations, and level of risk. E-consent is not a one-size-fits-all tool for trials, and its use should be carefully considered during the development of the trial protocol, in conjunction with patient and public involvement contributors, site staff and other trial stakeholders., (© 2024. The Author(s).)