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The COVID-19 pandemic has presented unique challenges for the clinical trial community, both in the rapid establishment of COVID-19 clinical trials and many existing non-COVID-19 studies either being temporarily paused (whether that is a complete pause or pause in some activities) and/or adapting their processes. Trial managers have played a key role in decision-making, undertaking risk assessments and adapting trial processes, working closely with other members of the research team. This article presents some of the ways in which trial management processes have been altered and the key role that trial managers have played. It has been born out of discussions between trial managers in the UK who are members of the UK Trial Managers’ Network (UKTMN), a national network of trial management professionals managing non-commercial trials. In these unprecedented times, clinical trials have faced many uncertainties and broad-ranging challenges encompassing a range of activities including prioritising patient safety amidst the pandemic, consenting and recruiting new participants into trials, data collection and management and intervention delivery. In many cases, recruitment has been paused whilst mitigations have been put in place to continue data collection. Innovative solutions have been implemented to ensure we continue, where possible, to deliver high-quality clinical trials. Technology has provided many solutions to these challenges, and trial managers have adapted to new ways of working whilst continuing to deliver their clinical trials. Trial management groups are now faced with new uncertainties around re-starting clinical trials, and it is unclear currently how this will go, though working together with sponsors, funders and site teams is clearly a priority. Clinical trial teams have worked together to ensure their trials have adapted quickly whilst ensuring participant safety is given utmost importance. There are clear examples where the trial community have come together to share experiences and expertise, and this should continue in the future to ensure the innovative practices developed become embedded in the design and conduct of clinical trials in the future.

Background Data collection consumes a large proportion of clinical trial resources. Each data item requires time and effort for collection, processing and quality control procedures. In general, more data equals a heavier burden for trial staff and participants. It is also likely to increase costs. Knowing the types of data being collected, and in what proportion, will be helpful to ensure that limited trial resources and participant goodwill are used wisely. Aim The aim of this study is to categorise the types of data collected across a broad range of trials and assess what proportion of collected data each category represents. Methods We developed a standard operating procedure to categorise data into primary outcome, secondary outcome and 15 other categories. We categorised all variables collected on trial data collection forms from 18, mainly publicly funded, randomised superiority trials, including trials of an investigational medicinal product and complex interventions. Categorisation was done independently in pairs: one person having in-depth knowledge of the trial, the other independent of the trial. Disagreement was resolved through reference to the trial protocol and discussion, with the project team being consulted if necessary. Key results Primary outcome data accounted for 5.0% (median)/11.2% (mean) of all data items collected. Secondary outcomes accounted for 39.9% (median)/42.5% (mean) of all data items. Non-outcome data such as participant identifiers and demographic data represented 32.4% (median)/36.5% (mean) of all data items collected. Conclusion A small proportion of the data collected in our sample of 18 trials was related to the primary outcome. Secondary outcomes accounted for eight times the volume of data as the primary outcome. A substantial amount of data collection is not related to trial outcomes. Trialists should work to make sure that the data they collect are only those essential to support the health and treatment decisions of those whom the trial is designed to inform.

Background There is an ethical imperative to offer the results of trials to those who participated. Existing research highlights that less than a third of trials do so, despite the desire of participants to receive the results of the trials they participated in. This scoping review aimed to identify, collate, and describe the available evidence relating to any aspect of disseminating trial results to participants. Methods A scoping review was conducted employing a search of key databases (MEDLINE, EMBASE, PsycINFO, and the Cumulative Index to Nursing & Allied Health Literature (CINAHL) from January 2008 to August 2019) to identify studies that had explored any aspect of disseminating results to trial participants. The search strategy was based on that of a linked existing review. The evidence identified describes the characteristics of included studies using narrative description informed by analysis of relevant data using descriptive statistics. Results Thirty-three eligible studies, including 12,700 participants (which included patients, health care professionals, trial teams), were identified and included. Reporting of participant characteristics (age, gender, ethnicity) across the studies was poor. The majority of studies investigated dissemination of aggregate trial results. The most frequently reported mode of disseminating of results was postal. Overall, the results report that participants evaluated receipt of trial results positively, with reported benefits including improved communication, demonstration of appreciation, improved retention, and engagement in future research. However, there were also some concerns about how well the dissemination was resourced and done, worries about emotional effects on participants especially when reporting unfavourable results, and frustration about the delay between the end of the trial and receipt of results. Conclusions This scoping review has highlighted that few high-quality evaluative studies have been conducted that can provide evidence on the best ways to deliver results to trial participants. There have been relatively few qualitative studies that explore perspectives from diverse populations, and those that have been conducted are limited to a handful of clinical areas. The learning from these studies can be used as a platform for further research and to consider some core guiding principles of the opportunities and challenges when disseminating trial results to those who participated.

Whilst the issues around early termination of randomised controlled trials (RCTs) are well documented in the literature, trials can also be temporarily suspended with the real prospect that they may subsequently restart. There is little guidance in the literature as to how to manage such a temporary suspension. In this paper, we describe the temporary suspension of a trial within our clinical trials unit because of concerns over the safety of transvaginal synthetic mesh implants. We also describe the challenges, considerations, and lessons learnt during the suspension that we are now applying in the current COVID-19 pandemic which has led to activities in many RCTs across the world undergoing a temporary suspension. There were three key phases within the temporary suspension: the decision to suspend, implementation of the suspension, and restarting. Each of these phases presented individual challenges which are discussed within this paper, along with the lessons learnt. There were obvious challenges around recruitment, delivery of the intervention, and follow-up. Additional challenges included communication between stakeholders, evolving risk assessment, updates to trial protocol and associated paperwork, maintaining site engagement, data-analysis, and workload within the trial team and Sponsor organisation. Based on our experience of managing a temporary suspension, we developed an action plan and guidance (see Additional File 1) for managing a significant trial event, such as a temporary suspension. We have used this document to help us manage the suspension of activities within our portfolio of trials during the current COVID-19 pandemic.

ObjectivesDo weekly prophylactic saline or acidic catheter washouts in addition to standard long-term catheter (LTC) care improve the outcomes of adults with LTC compared with standard LTC care only.DesignThree-arm superiority open-label randomised controlled trial.SettingUK community-based study.Participants80 adults with LTC (any type/route) ≥28 days in situ with no plans to discontinue and able to self-manage the washouts/study documentation with/without a carer.InterventionsRandomly allocated (26:27:27) to receive standard LTC care with weekly saline or weekly acidic or no prophylactic washouts for up to 24 months.Primary and secondary outcome measuresThe primary outcome was catheter blockage requiring intervention (per 1000 catheter days). Secondary outcomes were symptomatic catheter-associated urinary tract infection (S-CAUTI) requiring antibiotics, adverse events, participants’ quality of life and day-to-day activities, acceptability and adherence.ResultsOutcomes reported for 25 saline, 27 acidic and 26 control participants. LTC blockages (per 1000 catheter days) requiring treatment were 9.96, 10.53 and 20.92 in the saline, acidic and control groups, respectively. The incident rate ratio (IRR) favours the washout groups (saline 0.65 (97.5% CI 0.24 to 1.77); p=0.33 and acidic 0.59 (97.5% CI 0.22 to 1.63); p=0.25), although not statistically significant. The S-CAUTI rate (per 1000 catheter days) was 3.71, 6.72 and 8.05 in the saline, acidic and control groups, respectively. The IRR favours the saline group (saline 0.40 (97.5% CI 0.20 to 0.80); p=0.003 and acidic 0.98 (97.5% CI 0.54 to 1.78); p=0.93). The trial closed before reaching target recruitment due to reduced research capacity during the COVID-19 pandemic.ConclusionsEarly closure and small sample size limits our ability to provide a definite answer. However, the observed non-statistically significant differences over control are favourable for lower rates of LTC blockages without a concomitant rise in S-CAUTI. The results support a multinational randomised controlled trial of catheter washouts in patients with LTC to ascertain their clinical and cost-effectiveness.Trial registration numberISRCTN17116445.

ObjectivesTo explore trial participants’ experience of long-term catheters (LTC), the acceptability of washout policies, their experience of the CATHETER II trial (a randomised controlled trial comparing the clinical effectiveness of various washout policies versus no washout policy in preventing catheter associated complications in adults living with long-term catheters) and their satisfaction with the outcomes. The objectives of the healthcare professionals (HCPs) focus group and interview were to explore their attitudes towards weekly prophylactic catheter washout, views on the provision of training and participants’ ability to enact washout behaviours.MethodologyA longitudinal qualitative study embedded within the CATHETER II randomised controlled trial, which included semi-structured interviews and focus groups with participants from multiple trial sites. Data were analysed using the Theoretical Framework of Acceptability and Theoretical Domains Framework. This UK community-based study included 50 (24 female, 26 male) CATHETER II trial participants, aged between 23 and 100 years, with LTC and able to self-manage the washout and study documentation either independently or with the help of a carer. Seven HCPs (five female, two male) also participated.ResultsThe participants had positive attitudes towards weekly prophylactic saline or acidic catheter washouts and other trial elements, such as washout training, catheter calendar and monthly phone calls. Participants and HCPs found the ‘ask’ of the CATHETER II trial and the weekly self-administered prophylactic washout policies to be feasible. The participants reported that the catheter washout training provided during the trial enhanced their self-efficacy, skills and self-reported capability to carry out the washouts. Participants reported having positive outcomes from the weekly washout. These included reduced blockage, pain or infection, reduced need for HCP support and greater psychological reassurance. HCPs attested to the participants’ understanding of and adherence to the weekly washouts and other elements of the trial.ConclusionsThis study shows acceptability, feasibility and self-reported fidelity of the CATHETER II trial on a behavioural level. Self-management for prophylactic catheter washouts is both feasible and, following training, achievable without any need for additional support.Trial registration numberISRCTN17116445.

Background Autism and ADHD are heritable, co-occurrent, and associated with difficulties with executive functioning (cognitive and self-regulation skills which enable us to set and work toward goals). Executive function difficulties, and their negative impacts across cognitive, health and social domains, extend to individuals with first-degree relatives who are autistic or have ADHD, even if they do not meet thresholds for a clinical diagnosis themselves. Supporting executive function development in children with elevated autism traits, or a first-degree relative with autism or ADHD, addresses community priorities for early support to help achieve the best mental health, education and life outcomes. Methods This study will evaluate the feasibility and acceptability of a randomized controlled trial (RCT) of a parent-toddler programme entitled “Supporting Toddlers with a connection to autism or ADHD to develop strong Attention, Regulation and Thinking skills” (START). START is a neurodiversity-affirming programme, co-refined through extensive Patient and Public Involvement. Sixty parent-child dyads, in Oxford or Southampton (UK), will be randomized using Sealed Envelope by a researcher not involved in recruitment, delivery or outcome data collection to receive START or usual practice, on a 1:1 ratio. Children (20 months old) will be assessed using questionnaires completed by the parent (not blind to allocation) post-intervention (within 2 weeks of the end of the active intervention wave, when children are aged 27–31 months), and using parent questionnaires and a battery of executive function measures administered by researchers blind to allocation at baseline and follow-up (36 months old). START will be delivered in small groups to 30 parent-child dyads, in community settings. Discussion We will assess the feasibility of recruiting eligible participants to the study, the reliability of measures of implementation fidelity and degree of implementation fidelity achieved, the appropriateness of proposed outcome and mechanism measures, the acceptability of an RCT of the programme, parental adherence to the programme, logistics of programme delivery, and the acceptability of START, using mixed-method measures of engagement and satisfaction. Results will inform the design and implementation of a definitive RCT of START, and yield broader insights into the delivery and evaluation of complex early-years interventions in community settings. Trial registration ISRCTN registry ISRCTN99820028 https://doi.org/10.1186/ISRCTN99820028 .

Background Researchers often rely on trial participants to self-report clinical outcomes (for example, fractures, re-operations). Little information exists as to the ‘accuracy’ of participant-reported clinical outcomes, particularly in randomised controlled trials (RCTs). To help address this evidence gap, we report four case studies, nested within different RCTs where participant-reported clinical outcome data were compared with those reported by clinicians or extracted from medical notes. Methods Four publicly-funded RCTs with different methods of verifying participant-reported outcomes were identified. In KAT, the participants were asked about hospital admissions for any reason. Where it was thought to be relevant to the trial knee, further information was sought from the lead surgeon at the admitting site to confirm whether or not the admission was relevant to the trial knee. In REFLUX, participants were asked about hospital admissions for any reason. For participants who reported a re-operation, further information was sought from the lead surgeon at the admitting site to confirm this. In RECORD, participants were asked three questions regarding broken bones. Where low-trauma fractures were reported, clinical verification was sought, initially from the research nurse at the site. In CATHETER, participants were asked about urinary tract infections (UTIs), and a prescription of antibiotics was provided for the treatment of UTIs following urethral catheterisation. The GPs of those who reported a UTI were contacted to confirm that an antibiotic prescription had been issued for the suspected UTI. Results In KAT, 397 of 6882 (6%) participant-reported hospital admissions were confirmed as relevant to the trial knee. In REFLUX, 16 of 19 participants (84%) who appeared to have had a re-operation were confirmed as having had one. In RECORD, 473 of 781 (61%) fractures reported by participants were confirmed as being low-trauma fractures. In CATHETER, 429 of 830 participant-reported UTIs (52%) were confirmed as such by the GPs. Conclusions We used different approaches in our verification of participant-reported outcomes in clinical trials, and we believe there is no one optimal solution. Consideration of issues such as what information is sought from participants, the phrasing of questions, whether the medical records are a true ‘gold standard’ and costs and benefits to the RCT may help determine the appropriate approach.

Background Various washout policies are widely used in adults living with long-term catheters (LTC). There is currently insufficient evidence on the benefits and potential harms of prophylactic LTC washout policies in the prevention of blockages and other LTC-related adverse events, such as urinary tract infections. CATHETER II tests the hypothesis that weekly prophylactic LTC washouts (normal saline or citric acid) in addition to standard LTC care reduce the incidence of catheter blockage requiring intervention compared to standard LTC care only in adults living with LTC. Methods CATHETER II is a pragmatic three-arm open multi-centre superiority randomised controlled trial with an internal pilot, economic analysis, and embedded qualitative study. Eligible participants are adults aged ≥ 18 years, who have had a LTC in use for ≥ 28 days, have no plans to discontinue the use of the catheter, are able to undertake the catheter washouts, and complete trial documentation or have a carer able to help them. Participants are identified from general practitioner practices, secondary/tertiary care, community healthcare, care homes, and via public advertising strategies. Participants are randomised 1:1:1 to receive a weekly saline (0.9%) washout in addition to standard LTC care, a weekly citric acid (3.23%) washout in addition to standard LTC care or standard LTC care only. Participants and/or carers will receive training to administer the washouts. Patient-reported outcomes are collected at baseline and for 24 months post-randomisation. The primary clinical outcome is catheter blockage requiring intervention up to 24 months post-randomisation expressed per 1000 catheter days. Secondary outcomes include symptomatic catheter-associated urinary tract infection requiring antibiotics, catheter change, adverse events, NHS/ healthcare use, and impact on quality of life. Discussion This study will guide treatment decision-making and clinical practice guidelines regarding the effectiveness of various prophylactic catheter washout policies in men and women living with LTC. This research has received ethical approval from Wales Research Ethics Committee 6 (19/WA/0015). Trial registration ISRCTN ISRCTN17116445 . Registered prospectively on 06 November 2019

Background Stress urinary incontinence (SUI) is a frequent adverse effect for men undergoing prostate surgery. A large proportion (around 8% after radical prostatectomy and 2% after transurethral resection of prostate (TURP)) are left with severe disabling incontinence which adversely effects their quality of life and many are reliant on containment measures such as pads (27% and 6% respectively). Surgery is currently the only option for active management of the problem. The overwhelming majority of surgeries for persistent bothersome SUI involve artificial urinary sphincter (AUS) insertion. However, this is expensive, and necessitates manipulation of a pump to enable voiding. More recently, an alternative to AUS has been developed – a synthetic sling for men which elevates the urethra, thus treating SUI. This is thought, by some, to be less invasive, more acceptable and less expensive than AUS but clear evidence for this is lacking. The MASTER trial aims to determine whether the male synthetic sling is non-inferior to implantation of the AUS for men who have SUI after prostate surgery (for cancer or benign disease), judged primarily on clinical effectiveness but also considering relative harms and cost-effectiveness. Methods/design Men with urodynamic stress incontinence (USI) after prostate surgery, for whom surgery is judged appropriate, are the target population. We aim to recruit men from secondary care urological centres in the UK NHS who carry out surgery for post-prostatectomy incontinence. Outcomes will be assessed by participant-completed questionnaires and 3-day urinary bladder diaries at baseline, 6, 12 and 24 months. The 24-h urinary pad test will be used at baseline as an objective assessment of urine loss. Clinical data will be completed at the time of surgery to provide details of the operative procedures, complications and resource use in hospital. At 12 months, men will also have a clinical review to evaluate the results of surgery (including another 24-h pad test) and to identify problems or need for further treatment. Discussion A robust examination of the comparative effectiveness of the male synthetic sling will provide high-quality evidence to determine whether or not it should be adopted widely in the NHS. Trial registration International Standard Randomised Controlled Trial Registry: Number ISRCTN49212975 . Registered on 22 July 2013. First patient randomised on 29 January 2014.