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Abstract Background Animated short videos used to explain a concept or project are often called animated explainer videos (AEVs). AEVs can supplement or provide an alternative to participant information sheets as a means of giving information about clinical research to potential participants. Current use of AEVs tends to focus on the specifics of a particular trial, yet there are many common aspects of clinical research regardless of the interventions being investigated that can be poorly covered in current trial materials. The EXPLAIN initiative aimed to determine the top generic clinical trial topics considered most important by different UK trial stakeholders. The top three topics were then turned into AEVs and have been made freely available for use. Method A list of generic clinical trial topics which often need explaining to potential trial participants when they are approached to take part in research was developed. Using a two-round Delphi survey of stakeholder groups (trial participants, patients, members of the public, site staff and clinical trials unit staff), the list of topics was expanded and prioritised to identify the topics most in need of clear explanation. The top three topics formed the basis of three AEVs, co-developed with patient and public partners. Results Two hundred twenty-eight responses were received to the first round of the Delphi survey, and 167 of these respondents also completed the second round of the survey. The three topics prioritised for creation of animated explainer videos were as follows: (1) What is consent? (2) Who decides what treatment I get/What is randomisation? (3) Is it safe to take part in a trial/How do you know a trial is safe? Following virtual meetings with patient and public partners recruited from the Delphi respondents, a script for each AEV was co-produced before being developed into an AEV by a company specialising in animated video production. Conclusion There are a wide range of generic concepts in which the use of animated explainer videos could be useful to improve participant understanding of clinical research. Via consensus survey across multiple stakeholders, we have determined a hierarchy of the importance of explaining these concepts. We envisage that the three AEVs created from this project will form the basis of a readily accessible library of animations to be utilised by trialists.

Abstract Background Digital technologies, such as wearable devices and smartphone applications (apps), can enable the decentralisation of clinical trials by measuring endpoints in people’s chosen locations rather than in traditional clinical settings. Digital endpoints can allow high-frequency and sensitive measurements of health outcomes compared to visit-based endpoints which provide an episodic snapshot of a person’s health. However, there are underexplored challenges in this emerging space that require interdisciplinary and cross-sector collaboration. A multi-stakeholder Knowledge Exchange event was organised to facilitate conversations across silos within this research ecosystem. Methods A survey was sent to an initial list of stakeholders to identify potential discussion topics. Additional stakeholders were identified through iterative discussions on perspectives that needed representation. Co-design meetings with attendees were held to discuss the scope, format and ethos of the event. The event itself featured a cross-disciplinary selection of talks, a panel discussion, small-group discussions facilitated via a rolling seating plan and audience participation via Slido. A transcript was generated from the day, which, together with the output from Slido, provided a record of the day’s discussions. Finally, meetings were held following the event to identify the key challenges for digital endpoints which emerged and reflections and recommendations for dissemination. Results Several challenges for digital endpoints were identified in the following areas: patient adherence and acceptability; algorithms and software for devices; design, analysis and conduct of clinical trials with digital endpoints; the environmental impact of digital endpoints; and the need for ongoing ethical support. Learnings taken for next generation events include the need to include additional stakeholder perspectives, such as those of funders and regulators, and the need for additional resources and facilitation to allow patient and public contributors to engage meaningfully during the event. Conclusions The event emphasised the importance of consortium building and highlighted the critical role that collaborative, multi-disciplinary, and cross-sector efforts play in driving innovation in research design and strategic partnership building moving forward. This necessitates enhanced recognition by funders to support multi-stakeholder projects with patient involvement, standardised terminology, and the utilisation of open-source software.

Abstract Background It is essential that electronic data collection (EDC) systems are both compliant with regulations and the principles of Good Clinical Practice (GCP) to allow for the timely and accurate reporting of data including safety data. For clinical trials of investigational medicinal products (CTIMPs), investigators must immediately report to the sponsor any serious adverse event (SAE) that occurs in a site for which they are responsible. It is therefore expected that sponsors provide systems for timely review and reporting should a SAE be classified as a suspected unexpected serious adverse reaction (SUSAR). Challenges arise when data related to adverse events (AEs) needs to be re-entered for SAEs; this can be prone to error and may delay reporting. Additionally, recognising what has changed from an initial SAE report when an investigator responds to queries raised can cause errors. Method A multi-disciplinary working group came together from a UK academic clinical trials unit (CTU) to establish if an electronic system could be created in the unit’s open-source EDC system—REDCap, to manage SAEs in an efficient way. Results A module has been created in REDCap to facilitate electronic SAE reporting: enabling an AE form to automatically trigger an SAE form for any AE which is also a SAE, prepopulating relevant fields of the SAE form, reducing the risk of delay and error when entering data into the SAE form. The system has also been developed with an embedded code to allow for instant visual recognition of any data updated following reporting to allow the sponsor to immediately review and resolve SAEs in a timely manner, complying with UK regulatory reporting. This functionality ‘The eSAE Project’ is now an active project for all of our new trials where data collection is undertaken using the REDCap system. Conclusion The eSAE Project coded into REDCap offers a unique way of populating SAE forms with information already entered in the initial AE forms as applicable, coupled with highlighting any updates during the lifetime of the SAE for sponsors to identify any new information that needs to be reassessed to process and report the SAE.

Abstract 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 Background Use of a person’s name in a text message has been shown to be effective in instigating behaviour change. We evaluated the effectiveness of a personalised text message (including the recipient’s name) versus a standardised text message for prompting a response from trial participants to complete and return postal follow-up questionnaires. Methods Using a randomised study within a trial (SWAT) embedded within the host GRASP (Getting it Right: Addressing Shoulder Pain) trial, participants who provided a mobile telephone number were randomised (1:1) by a central computer system to receive either (1) a personalised text message which included their name or (2) a standard text message. Text messages were sent by the trial office on the same day as the 6-month GRASP follow-up questionnaire. The primary outcome was questionnaire response rate, defined as the proportion of 6-month GRASP follow-up questionnaires returned by participants. Secondary outcomes included time to response, the proportion of participants sent a reminder follow-up questionnaire, and cost. Results Between March 2017 and May 2019 (recruitment period for GRASP trial), 618 participants were randomised to a personalised (n = 309) or standard (n = 309) text message and all were included in the analysis. The overall questionnaire response rate was 87% (n = 537/618); 90% (n = 277/309) of participants responded in the personalised text message group compared to 84% (n = 260/309) in the standard text message group (relative risk (RR) 1.07; 95% CI 1.00 to 1.13). Participants randomised to receive the personalised text message were more likely to return their initial postal questionnaire than those who received the standard text message (n = 185/309; 60% vs. n = 160/309; 52%) (RR 1.16; 95% CI 1.00 to 1.33); this represents an absolute percentage difference between intervention groups of 8%. Post hoc subgroup analysis showed that males under 65 years were the group most likely to return their initial questionnaire if they received a personalised text message. Conclusion Overall, participants who received a personalised text message were more likely to return their questionnaire than those who received the standard text message. Trial registration GRASP Trial ISRCTN16539266 ; SWAT Repository ID 35

Abstract Background Hand osteoarthritis (OA) is a common condition, causing pain, stiffness and reduced quality of life. Incidence is higher amongst women, particularly around the age of the menopause. Whilst the relationship between sex hormones and OA has been studied in vitro, in epidemiological studies and in clinical trials of hormone replacement therapy (HRT), this study is the first to investigate the effect of estrogen-containing therapy on hand pain in post-menopausal women with symptomatic hand OA in a randomised study design. Methods This is a feasibility study of a double-blinded placebo-controlled intervention with 1:1 randomisation to either a combination of conjugated estrogens 0.45 mg and bazedoxifene acetate 20 mg (Duavive) or placebo. The target population is post-menopausal women with symptomatic hand OA, aiming to recruit 60–90 study participants. The primary objective is to assess the feasibility of a future fully powered randomised controlled trial (RCT). Participants will take the study medication for 24 weeks and be followed up for 28 weeks after randomisation. The primary outcomes used to determine feasibility are eligible participant identification rates and routes; recruitment, randomisation and retention rates of eligible participants; study medication compliance; and the likelihood of unintentional unblinding. Secondary outcomes include measures of hand pain, function, appearance and menopausal symptoms. An end of study questionnaire and focus groups will help to refine the final protocol for a full study. Discussion Identifying new treatments for symptomatic hand OA is a recognised research priority. The study will help us to understand whether there are sufficient interested and eligible individuals in this target population who would consider HRT for their hand symptoms. It will provide proof-of-concept RCT data on the effects of HRT on hand pain and other clinically relevant outcomes in this population. The study will gain valuable information on the feasibility of a full RCT and how best to run this. The findings will be published in a peer-reviewed journal and presented at a relevant conference. Trial registration ISRCTN12196200 registered on 15 January 2019.

Abstract Background Survivors of critical illness have significant psychopathological comorbidity. The treatments offered by primary health care professionals to affected patients are unstudied. Aim To report the psychological interventions after GPs received notification of patients who showed severe symptoms of anxiety, depression or Post-Traumatic Stress Disorder. Methods Design: Multi-centre prospective cohort sub-study of the ICON study. Setting: NHS primary care in the United Kingdom. Participants: Adult patients, November 2006–October 2010 who had received at least 24 h of intensive care, where the general practitioner recorded notification that the patient had reported severe symptoms or caseness using the Hospital Anxiety and Depression Scale (HADS) or the Post-Traumatic Stress Disorder Check List-Civilian (PCL-C). Interventions: We notified general practitioners (GPs) by post if a patient reported severe symptoms or caseness and sent a postal questionnaire to determine interventions after notification. Main outcome measure: Primary or secondary healthcare interventions instigated by general practitioners following notification of a patient’s caseness. Results Of the 11,726 patients, sent questionnaire packs containing HADS and PCL-C, 4361 (37%) responded. A notification of severe symptoms was sent to their GP in 25% (1112) of cases. Of notified GPs, 65% (725) responded to our postal questionnaire. Of these 37% (266) had no record of receipt of the original notification. Of the 459 patients where GPs had record of notification (the study group for this analysis), 21% (98) had pre-existing psychopathology. Of those without a pre-existing diagnosis 45% (162) received further psychological assessment or treatment. GP screening or follow-up alone occurred in 18% (64) whilst 27% (98) were referred to mental health services or received drug therapy following notification. Conclusions Postal questionnaire identifies a burden of psychopathology in survivors of critical illness that have otherwise gone undiagnosed following discharge from an intensive care unit (ICU). After being alerted to the presence of psychological symptoms, GPs instigate treatment in 27% and augmented surveillance in 18% of cases. Trial registration ISRCTN69112866 (assigned 02/05/2006).

Abstract Background Azithromycin is an orally active synthetic macrolide antibiotic with a wide range of anti-bacterial, anti-inflammatory and antiviral properties. It is a safe, inexpensive, generic licenced drug available worldwide and manufactured to scale and is a potential candidate therapy for pandemic coronavirus disease 2019 (COVID-19). Azithromycin was widely used to treat severe SARS-CoV and MERS-CoV, but to date, no randomised data are available in any coronavirus infections. Other ongoing trials are exploring short courses of azithromycin either in early disease, within the first 7 days of symptoms, when azithromycin’s antiviral properties may be important, or late in disease when anti-bacterial properties may reduce the risk of secondary bacterial infection. However, the molecule’s anti-inflammatory properties, including suppression of pulmonary macrophage-derived pro-inflammatory cytokines such as interleukins-1β, -6, -8, and -18 and cytokines G-CSF and GM-CSF may provide a distinct therapeutic benefit if given in as a prolonged course during the period of progression from moderate to severe disease. Methods ATOMIC2 is a phase II/III, multi-centre, prospective, open-label, two-arm randomised superiority clinical trial of azithromycin versus standard care for adults presenting to hospital with COVID-19 symptoms who are not admitted at initial presentation. We will enrol adults, ≥ 18 years of age assessed in acute hospitals in the UK with clinical diagnosis of COVID-19 infection where management on an ambulatory care pathway is deemed appropriate. Participants will be randomised in a 1:1 ratio to usual care or to azithromycin 500 mg orally daily for 14 days with telephone follow-up at days 14 and 28. The primary objective is to compare the proportion with either death or respiratory failure requiring invasive or non-invasive mechanical ventilation over 28 days from randomisation. Secondary objectives include mortality/respiratory failure in those with a PCR-confirmed diagnosis; all-cause mortality; progression to pneumonia; progression to severe pneumonia; peak severity of illness and mechanistic analysis of blood and nasal biomarkers. Discussion This trial will determine the clinical utility of azithromycin in patients with moderately severe, clinically diagnosed COVID-19 and could be rapidly applicable worldwide. Trial registration ClinicalTrials.gov NCT04381962 . Registered on 11 May 2020. EudraCT identifier 2020-001740-26 . Opened for accrual on 29 May 2020.