Approaches and experiences implementing remote, electronic consent at the Leeds Clinical Trials Research Unit.

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.

Intervention to reduce sedentary behaviour and improve outcomes after stroke (Get Set Go): a study protocol for the process evaluation of a pilot cluster randomised controlled trial (RECREATE).

INTRODUCTION: Stroke survivors spend long periods of time engaging in sedentary behaviour (SB) even when their functional recovery is good. In the RECREATE programme, an intervention aimed at reducing SB ('Get Set Go') will be implemented and evaluated in a pragmatic external pilot cluster randomised controlled trial with embedded process and economic evaluations. We report the protocol for the process evaluation which will address the following objectives: (1) describe and clarify causal assumptions about the intervention, and its mechanisms of impact; (2) assess implementation fidelity; (3) explore views, perceptions and acceptability of the intervention to staff, stroke survivors and their carers; (4) establish the contextual factors that influence implementation, intervention mechanisms and outcomes. METHODS AND ANALYSIS: This pilot trial will be conducted in 15 UK-based National Health Service stroke services. This process evaluation study, underpinned by the Medical Research Council guidance, will be undertaken in six of the randomised services (four intervention, two control). Data collection includes the following: observations of staff training sessions, non-participant observations in inpatient and community settings, semi-structured interviews with staff, patients and carers, and documentary analysis of key intervention components. Additional quantitative implementation data will be collected in all sites. Training observations and documentary analysis data will be summarised, with other observational and interview data analysed using thematic analysis. Relevant theories will be used to interpret the findings, including the theoretical domains framework, normalisation process theory and the theoretical framework of acceptability. Anticipated outputs include the following: recommendations for intervention refinements (both content and implementation); a revised implementation plan and a refined logic model. ETHICS AND DISSEMINATION: The study was approved by Yorkshire & The Humber - Bradford Leeds Research Ethics Committee (REC reference: 19/YH/0403). Findings will be disseminated via peer review publications, and national and international conference presentations. TRIAL REGISTRATION NUMBER: ISRCTN82280581.

A cluster randomised controlled trial, process and economic evaluation of quality improvement collaboratives aligned to a national audit to improve the care for people with diabetes (EQUIPD): study protocol.

BACKGROUND: People with type 1 diabetes and raised glucose levels are at greater risk of retinopathy, nephropathy, neuropathy, cardiovascular disease, sexual health problems and foot disease. The UK National Institute for Health and Care Excellence (NICE) recommends continuous subcutaneous 'insulin pump' therapy for people with type 1 diabetes whose HbA1c is above 69 mmol/mol. Insulin pump use can improve quality of life, cut cardiovascular risk and increase treatment satisfaction. About 90,000 people in England and Wales meet NICE criteria for insulin pumps but do not use one. Insulin pump use also varies markedly by deprivation, ethnicity, sex and location. Increasing insulin pump use is a key improvement priority. Audit and feedback is a common but variably effective intervention. Limited capabilities of healthcare providers to mount effective responses to feedback from national audits, such as the National Diabetes Audit (NDA), undermines efforts to improve care. We have co-developed a theoretically and empirically informed quality improvement collaborative (QIC) to strengthen local responses to feedback with patients and carers, national audits and healthcare providers. We will evaluate whether the QIC improves the uptake of insulin pumps following NDA feedback. METHODS: We will undertake an efficient cluster randomised trial using routine data. The QIC will be delivered alongside the NDA to specialist diabetes teams in England and Wales. Our primary outcome will be the proportion of people with type 1 diabetes and an HbA1c above 69 mmol/mol who start and continue insulin pump use during the 18-month intervention period. Secondary outcomes will assess change in glucose control and duration of pump use. Subgroup analyses will explore impacts upon inequalities by ethnicity, sex, age and deprivation. A theory-informed process evaluation will explore diabetes specialist teams' engagement, implementation, fidelity and tailoring through observations, interviews, surveys and documentary analysis. An economic evaluation will micro-cost the QIC, estimate cost-effectiveness of NDA feedback with QIC and estimate the budget impact of NHS-wide QIC roll out. DISCUSSION: Our study responds to a need for more head-to-head trials of different ways of reinforcing feedback delivery. Our findings will have implications for other large-scale audit and feedback programmes. TRIAL REGISTRATION: ISRCTN82176651 Registered 18 October 2022.

RECREATE: a study protocol for a multicentre pilot cluster randomised controlled trial (cRCT) in UK stroke services evaluating an intervention to reduce sedentary behaviour in stroke survivors (Get Set Go) with embedded process and economic evaluations.

INTRODUCTION: Sedentary behaviour (sitting or lying during waking hours without being otherwise active) is strongly associated with adverse health outcomes, including all-cause, cancer and cardiovascular mortality in adults. Stroke survivors are consistently reported as being more sedentary than healthy age-matched controls, spending more hours sedentary daily and sustaining longer unbroken bouts of sedentary time. An evidence-based and clinically feasible intervention ('Get Set Go') was developed. A pragmatic definitive trial to evaluate Get Set Go was planned; however, due to the unprecedented effects of the COVID-19 pandemic on National Health Service (NHS) services this study was reduced in size and scope to become an external pilot trial. We report the protocol for this external pilot trial, which aims to undertake a preliminary exploration of whether Get Set Go is likely to improve ability to complete extended activities of daily living in the first year post-stroke and inform future trial designs in stroke rehabilitation. METHODS AND ANALYSIS: This study is a pragmatic, multicentre, two-arm, external pilot cluster randomised controlled trial with embedded process and economic evaluations. UK-based stroke services will be randomised 1:1 to the intervention (usual care plus Get Set Go) or control (usual care) arm. Fifteen stroke services will recruit 300-400 stroke inpatient and carer participants, with follow-up at 6, 12 and 24 months. The proposed primary endpoint is stroke survivor self-reported Nottingham Extended Activities of Daily Living scale at 12 months. Endpoint analyses will be exploratory and provide preliminary estimates of intervention effect. The process evaluation will provide valuable information on intervention fidelity, acceptability and how it can be optimised. ETHICS AND DISSEMINATION: The study has been approved by Yorkshire and The Humber - Bradford-Leeds Research Ethics Committee (Ref: 19/YH/0403). Results will be disseminated through journal publications and conference presentations. TRIAL REGISTRATION NUMBER: This trial was registered prospectively on 01 April 2020 (ISRCTN ref: ISRCTN82280581).

An intervention to support stroke survivors and their carers in the longer term: results of a cluster randomised controlled feasibility trial (LoTS2Care).

BACKGROUND: To address the limited provision of longer-term stroke care, we conducted a programme of research (LoTS2Care) to develop and test an intervention to form part of a replicable longer-term care strategy. New Start, a programme of facilitated self-management, was developed to be delivered at 6 months post-stroke by trained facilitators. Here, we report the findings from the final workstream of this programme, which aimed to evaluate the feasibility and acceptability of implementing a future definitive cluster randomised controlled trial of the developed intervention (New Start) to support stroke survivors and their carers in the longer term. METHODS: A feasibility cluster randomised controlled trial was conducted in English and Welsh NHS stroke services. Stroke services (clusters) were randomised on a 1:1 basis to implement New Start or continue with usual care only. Community-dwelling stroke survivors between 4 and 6 months post-stroke were invited to participate in the trial by post. Outcome measures were collected via post at 3, 6 and 9 months after recruitment. Recruitment and follow-up rates, delivery and uptake of the intervention, data collection feasibility (including postal outcome measures of health and disability, mental well-being at 3, 6, and 9 months post-recruitment) and safety were assessed. RESULTS: Ten stroke services were recruited. A total of 1127 stroke survivors were screened for participation, and 269 were registered (New Start, n = 145; usual care, n = 124). Retention was high with 239 (89%) stroke survivors being available for follow-up at 9 months, and high return rates of postal questionnaires were achieved (80.3% at 9 months). Intervention training was successfully delivered, and New Start was offered to 95.2% of trial participants in the intervention arm. Uptake was variable, however, ranging from 11.8 to 75.0%. There were no safety concerns. CONCLUSIONS: Stroke service recruitment and longer-term stroke survivor postal recruitment and outcome data collection are feasible; however, refinement of intervention targeting and delivery is required prior to undertaking a definitive trial. TRIAL REGISTRATION: ISRCTN38920246. Registered 22 June 2016 ( http://www.isrctn.com/ISRCTN38920246 ).

Using routine healthcare data to evaluate the impact of the Medicines at Transitions Intervention (MaTI) on clinical outcomes of patients hospitalised with heart failure: protocol for the Improving the Safety and Continuity Of Medicines management at Transitions of care (ISCOMAT) cluster randomised controlled trial with embedded process evaluation, health economics evaluation and internal pilot.

INTRODUCTION: Heart failure affects 26 million people globally, approximately 900 thousand people in the UK, and is increasing in incidence. Appropriate management of medicines for heart failure at the time of hospital discharge reduces readmissions, improves quality of life and increases survival. The Improving the Safety and Continuity Of Medicines management at Transitions (ISCOMAT) trial tests the effectiveness of the Medicines at Transition Intervention (MaTI), which aims to enhance self-care and increase community pharmacy involvement in the medicines management of heart failure patients. METHODS AND ANALYSIS: ISCOMAT is a parallel-group cluster randomised controlled trial, randomising 42 National Health Service trusts with cardiology wards in England on a 1:1 basis to implement the MaTI or treatment as usual. Around 2100 patients over the age of 18 admitted to hospital with heart failure with at least moderate left ventricular systolic dysfunction within the last 5 years, and planned discharge to the geographical area of the cluster will be recruited. The MaTI consists of training for staff, a toolkit for participants, transfer of discharge information to community pharmacies and a medicines reconciliation/review. Treatment as usual is determined by local policy and practices. The primary outcome is a composite of all-cause mortality and heart failure-related hospitalisation at 12 months postregistration obtained from national electronic health records. The key secondary outcome is continued prescription of guideline-indicated therapies at 12 months measured via patient-reported data and Hospital Episode Statistics. The trial contains a parallel mixed-methods process evaluation and an embedded health economics study. ETHICS AND DISSEMINATION: The study obtained approval from the Yorkshire and the Humber-Bradford Leeds Research Ethics Committee; REC reference 18/YH/0017. Findings will be disseminated via academic and policy conferences, peer-reviewed publications and social media. Amendments to the protocol are disseminated to all relevant parties as required. TRIAL REGISTRATION NUMBER: ISRCTN66212970; Pre-results.

Effectiveness of Enhanced Performance Feedback on Appropriate Use of Blood Transfusions: A Comparison of 2 Cluster Randomized Trials.

Importance: Auditing and feedback are frequently used to improve patient care. However, it remains unclear how to optimize feedback effectiveness for the appropriate use of treatments such as blood transfusion, a common but costly procedure that is more often overused than underused. Objective: To evaluate 2 theoretically informed feedback interventions to improve the appropriate use of blood transfusions. Design, Setting, and Participants: Two sequential, linked 2 × 2 cluster randomized trials were performed in hospitals in the UK participating in national audits of transfusion for perioperative anemia and management of hematological disorders. Data were collected for a surgical trial from October 1, 2014, to October 31, 2016, with follow-up completed on October 31, 2016. Data were collected for a hematological trial through follow-up from July 1, 2015, to June 30, 2017. Trial data were analyzed from November 1, 2016, to June 1, 2019. Interventions: Hospitals were randomized to standard content or enhanced content to improve feedback clarity and usability and to standard support or enhanced support for staff to act on feedback. Main Outcomes and Measures: The primary end point was appropriateness of transfusions audited at 12 months. Secondary end points included volume of transfusions (aiming for reductions at patient and cluster levels) and transfusion-related adverse events and reactions. Results: One hundred thirty-five of 152 eligible clusters participated in the surgical audit (2714 patients; mean [SD] age, 74.9 [14.0] years; 1809 women [66.7%]), and 134 of 141 participated in the hematological audit (4439 patients; median age, 72.0 [IQR, 64.0-80.0] years; 2641 men [59.5%]). Fifty-seven of 69 clusters (82.6%) in the surgical audit randomized to enhanced content downloaded reports compared with 52 of 66 clusters (78.8%) randomized to standard reports. Fifty-nine of 68 clusters (86.8%) randomized to enhanced support logged onto the toolkit. The proportion of patients with appropriate transfusions was 0.184 for standard content and 0.176 for enhanced content (adjusted odds ratio [OR], 0.91 [97.5% CI, 0.61-1.36]) and 0.181 for standard support and 0.180 for enhanced support (adjusted OR, 1.05 [97.5% CI, 0.68-1.61]). For the hematological audit, 53 of 66 clusters (80.3%) randomized to enhanced content downloaded the reports compared with 53 of 68 clusters (77.9%) randomized to standard content. Forty-nine of 67 clusters sites (73.1%) assigned to enhanced support logged into the toolkit at least once. The proportion of patients with appropriate transfusions was 0.744 for standard content and 0.714 for enhanced content (adjusted OR, 0.81 [97.5% CI, 0.56-1.12]), and 0.739 for standard support and 0.721 for enhanced support (adjusted OR, 0.96 [97.5% CI, 0.67-1.38]). Conclusions and Relevance: This comparison of cluster randomized trials found that interventions to improve feedback usability and guide local action were no more effective than standard feedback in increasing the appropriate use of blood transfusions. Auditing and feedback delivered at scale is a complex and costly program; therefore, effective responses may depend on developing robust local quality improvement arrangements, which can be evaluated using rigorous experimental designs embedded within national programs. Trial Registration: isrctn.org Identifier: ISRCTN15490813.

An intervention to support stroke survivors and their carers in the longer term (LoTS2Care): study protocol for a cluster randomised controlled feasibility trial.

BACKGROUND: Despite the evidence that many stroke survivors report longer term unmet needs, the provision of longer term care is limited. To address this, we are conducting a programme of research to develop an evidence-based and replicable longer term care strategy. The developed complex intervention (named New Start), which includes needs identification, exploration of social networks and components of problem solving and self-management, was designed to improve quality of life by addressing unmet needs and increasing participation. METHODS/DESIGN: A multicentre, cluster randomised controlled feasibility trial designed to inform the design of a possible future definitive cluster randomised controlled trial (cRCT) and explore the potential clinical and cost-effectiveness of New Start. Ten stroke services across the UK will be randomised on a 1:1 basis either to implement New Start or continue with usual care only. New Start will be delivered by trained facilitators and will be offered to all stroke survivors within the services allocated to the intervention arm. Stroke survivors will be eligible for the trial if they are 4-6 months post-stroke and residing in the community. Carers (if available) will also be invited to take part. Invitation to participate will be initiated by post and outcome measures will be collected via postal questionnaires at 3, 6 and 9 months after recruitment. Outcome data relating to perceived health and disability, wellbeing and quality of life as well as unmet needs will be collected. A 'study within a trial' (SWAT) is planned to determine the most acceptable format in which to provide the postal questionnaires. Details of health and social care service usage will also be collected to inform the economic evaluation. The feasibility of recruiting services and stroke survivors to the trial and of collecting postal outcomes will be assessed and the potential for effectiveness will be investigated. An embedded process evaluation (reported separately) will assess implementation fidelity and explore and clarify causal assumptions regarding implementation. DISCUSSION: This feasibility trial with embedded process evaluation will allow us to gather important and detailed data regarding methodological and implementation issues to inform the design of a possible future definitive cRCT of this complex intervention. TRIAL REGISTRATION: ISRCTN38920246 . Registered 22 June 2016.