The overlap between randomised evaluations of recruitment and retention interventions: An updated review of recruitment (Online Resource for Recruitment in Clinical triAls) and retention (Online Resource for Retention in Clinical triAls) literature.

BACKGROUND: The Online Resource for Recruitment in Clinical triAls (ORRCA) and the Online Resource for Retention in Clinical triAls (ORRCA2) were established to organise and map the literature addressing participant recruitment and retention within clinical research. The two databases are updated on an ongoing basis using separate but parallel systematic reviews. However, recruitment and retention of research participants is widely acknowledged to be interconnected. While interventions aimed at addressing recruitment challenges can impact retention and vice versa, it is not clear how well they are simultaneously considered within methodological research. This study aims to report the recent update of ORRCA and ORRCA2 with a special emphasis on assessing crossover of the databases and how frequently randomised studies of methodological interventions measure the impact on both recruitment and retention outcomes. METHODS: Two parallel systematic reviews were conducted in line with previously reported methods updating ORRCA (recruitment) and ORRCA2 (retention) with publications from 2018 and 2019. Articles were categorised according to their evidence type (randomised evaluation, non-randomised evaluation, application and observation) and against the recruitment and retention domain frameworks. Articles categorised as randomised evaluations were compared to identify studies appearing in both databases. For randomised studies that were only in one database, domain categories were used to assess whether the methodological intervention was likely to impact on the alternate construct. For example, whether a recruitment intervention might also impact retention. RESULTS: In total, 806 of 17,767 articles screened for the recruitment database and 175 of 18,656 articles screened for the retention database were added as result of the update. Of these, 89 articles were classified as 'randomised evaluation', of which 6 were systematic reviews and 83 were randomised evaluations of methodological interventions. Ten of the randomised studies assessed recruitment and retention and were included in both databases. Of the randomised studies only in the recruitment database, 48/55 (87%) assessed the content or format of participant information which could have an impact on retention. Of the randomised studies only in the retention database, 6/18 (33%) assessed monetary incentives, 4/18 (22%) assessed data collection location and methods and 3/18 (17%) assessed non-monetary incentives, all of which could have an impact on recruitment. CONCLUSION: Only a small proportion of randomised studies of methodological interventions assessed the impact on both recruitment and retention despite having a potential impact on both outcomes. Where possible, an integrated approach analysing both constructs should be the new standard for these types of evaluations to ensure that improvements to recruitment are not at the expense of retention and vice versa.

Understanding implementation of findings from trial method research: a mixed methods study applying implementation frameworks and behaviour change models.

BACKGROUND: Trial method research produces recommendations on how to best conduct trials. However, findings are not routinely implemented into practice. To better understand why, we conducted a mixed method study on the challenges of implementing trial method research findings into UK-based clinical trial units. METHODS: Three stages of research were conducted. Firstly, case studies of completed projects that provided methodological recommendations were identified within trial design, conduct, analysis, and reporting. These case studies were used as survey examples to query obstacles and facilitators to implementing method research. Survey participants were experienced trial staff, identified via email invitations to UK clinical trial units. This survey assessed the case studies' rates of implementation, and demographic characteristics of trial units through the Consolidated Framework for Implementation Research. Further, interviews were conducted with senior members of trial units to explore obstacles and facilitators in more detail. Participants were sampled from trial units that indicated their willingness to participate in interviews following the survey. Interviews, and analysis, were structured via the Capability, Opportunity, Motivation Model of Behaviour. Finally, potential strategies to leverage lessons learned were generated via the Behaviour Change Wheel. RESULTS: A total of 27 UK trial units responded to the survey. The rates of implementation across the case studies varied, with most trial units implementing recommendations in trial conduct and only few implementing recommendations in reporting. However, most reported implementing recommendations was important but that they lacked the resources to do so. A total of 16 senior members of trial units were interviewed. Several themes were generated from interviews and fell broadly into categories related to the methods recommendations themselves, the trial units, or external factors affecting implementation. Belief statements within themes indicated resources issues and awareness of recommendations as frequent implementation obstacles. Participation in trial networks and recommendations packaged with relevant resources were cited frequently as implementation facilitators. These obstacles and facilitators mirrored results from the survey. Results were mapped, via the Behaviour Change Wheel, to intervention functions likely to change behaviours of obstacles and facilitators identified. These intervention functions were developed into potential solutions to reduce obstacles and enhance facilitators to implementation. CONCLUSIONS: Several key areas affecting implementation of trial method recommendations were identified. Potential methods to enhance facilitators and reduce obstacles are suggested. Future research is needed to refine these methods and assess their feasibility and acceptability.

Developing strategies to address disparities in retention communication during the consent discussion: development of a behavioural intervention.

BACKGROUND: Clinical trials are essential to evidence-based medicine. Their success relies on recruitment and retention of participants: problems with either can affect validity of results. Past research on improving trials has focused on recruitment, with less on retention, and even less considering retention at the point of recruitment, i.e., what retention-relevant information is shared during consent processes. The behaviour of trial staff communicating this information during consent is likely to contribute to retention. So, developing approaches to mitigate issues in retention at the point of consent is necessary. In this study, we describe the development of a behavioural intervention targeting the communication of information important to retention during the consent process. METHODS: We applied the Theoretical Domains Framework and Behaviour Change Wheel to develop an intervention aimed at changing the retention communication behaviours of trial staff. Building on findings from an interview study to understand the barriers/facilitators to retention communication during consent, we identified behaviour change techniques that could moderate them. These techniques were grouped into potential intervention categories and presented to a co-design group of trial staff and public partners to discuss how they might be packaged into an intervention. An intervention was presented to these same stakeholders and assessed for acceptability through a survey based on the Theoretical Framework of Acceptability. RESULTS: Twenty-six behaviour change techniques were identified with potential to change communication of retention-information at consent. Six trial stakeholders in the co-design group discussed means for implementing these techniques and agreed the available techniques could be most effective within a series of meetings focussed on best practices for communicating retention at consent. The proposed intervention was deemed acceptable through survey results. CONCLUSION: We have developed an intervention aimed at facilitating the communication of retention at informed consent through a behavioural approach. This intervention will be delivered to trial staff and will add to the available strategies for trials to improve retention.

What influences communication about retention in randomised trials: a multi-trial, theory-based analysis exploring trial staff perspectives.

BACKGROUND: Retention (participants completing a trial) is a persistent, and often under-studied, challenge within clinical trials. Research on retention has focussed on understanding the actions of participants who decide to remain or withdraw from trial participation and developing interventions to target improvements. To better understand how trial staff may influence participants to remain or withdraw from trials, it is important to explore the experiences of staff that recruit and retain said participants and how the process of recruitment impacts retention. METHODS: Two qualitative interview studies informed by the Theoretical Domains Framework (TDF) were conducted with staff involved in various stages of clinical trials. The first set of interviews were focussed on staff perceptions about why participants failed to be retained and what helped to keep others engaged in trials, but also explored more generally what strategies or factors contributed to retention in trials. The second set of interviews were focussed on staff perceptions specifically about the recruitment and informed consent process and how that may influence trial retention. All interviews were analysed using the TDF and assigned to relevant behavioural domains according to perceived barriers/facilitators of the target behaviour. Belief statements were generated, summarising the narrative content of related responses within these behavioural domains. These belief statements were further analysed for themes that captured higher order relationships between separate beliefs within and between behavioural domains. RESULTS: Twenty-five participants (9 retention staff and 16 recruitment staff) were interviewed. Themes describing the barriers/facilitators to retention broadly, and to communication of retention information at consent, were generated. Four themes on retention broadly and six themes on communication of retention information at consent were identified. Overall, beliefs within all fourteen TDF domains populated these themes. CONCLUSIONS: This study explored staff perspectives on retention and how they interpret their behaviour as contributing to retention success. Perspectives varied considerably but several key themes regarding communication were seen consistently. Specific barriers and facilitators within these findings will serve to guide the design of a behavioural intervention aimed at addressing issues within retention. Findings contribute to a notable gap in the literature on staff behaviour in trials and on retention generally.

Behavioural optimisation to address trial conduct challenges: case study in the UK-REBOA trial.

BACKGROUND: Clinical trials comprise multiple processes at various stages of the trial lifecycle. These processes often involve complex behaviours such as recruiting vulnerable patient populations and clinicians having to deliver complex trial interventions successfully. Few studies have utilised a behavioural framework to assess challenges and develop strategies for effective trial recruitment and delivery of trial interventions. This study reports the application of an innovative methodological approach to understand core trial processes, namely recruitment and intervention delivery, using a behavioural science approach to develop strategies designed to mitigate trial process problems. METHODS: The UK-REBOA trial aims to evaluate the clinical and cost-effectiveness of resuscitative endovascular balloon occlusion of the aorta (a novel intervention) in injured patients with exsanguinating haemorrhage. A behavioural investigation ('diagnosis') was conducted using theory-informed (Theoretical Domains Framework, TDF) semi-structured interviews with site staff from the UK-REBOA trial to examine trial processes which could be improved in relation to trial recruitment and delivery of the intervention. Interviews were analysed using the TDF to identify influences on behaviour, which were then mapped to techniques for behaviour change and developed into potential solutions. RESULTS: The behavioural diagnosis of the challenges experienced during trial processes highlighted factors relevant to a range of TDF domains: Skills, Environmental context and resources, Beliefs about capabilities, Beliefs about consequences, Social influences, and Memory, attention, and decision-making processes. Within the solution development phase, we identified 24 suitable behaviour change techniques that were developed into proposed solutions to target reported process problems with the aim of changing behaviour to improve recruitment and/or intervention delivery. Proposed solutions included targeted changes to trial training content, suggestions to restructure the environment (e.g. reinforced the purpose of the trial with information about the social and environmental consequences) and other strategies to reduce barriers to recruitment and intervention delivery. CONCLUSIONS: This study demonstrates the feasibility of applying a behavioural approach to investigate ('diagnose') behavioural trial process problems and subsequently develop and implement targeted solutions ('treatment') in an active trauma trial. Understanding the factors that affected behaviour, attitudes and beliefs in this trauma trial allowed us to implement theoretically informed, evidence-based solutions designed to enhance trial practices. TRIAL REGISTRATION: ISRCTN 16,184,981.

Behavioural approaches to recruitment and retention in clinical trials: a systematic mapping review.

OBJECTIVES: To identify studies that applied behavioural approaches to issues of recruitment and/or retention to trials; to describe these approaches; and to identify gaps for future research. DESIGN: Systematic mapping review of research undertaken in clinical trials within peer-reviewed sources. Review participants were individuals involved in clinical trials, including trial staff, participants, potential participants and former participants. DATA SOURCES: MEDLINE, EMBASE, CINAHL, ERIC, PsycINFO, Web of Science and ASSIA from inception to 15 January 2020 with no date or language restrictions. ELIGIBILITY CRITERIA: Studies within the context of clinical trials reporting the barriers/facilitators to recruitment and retention, or developing/evaluating solutions to said barriers/facilitators, using a behavioural approach. RESULTS: 31 articles were included. Recruitment-focused studies (n=22, 71%) represented the majority. Studies tended to focus on participant behaviours (n=22, 71%). Underserved populations (n=11, 35%) were a notable subset of studies. Most studies (n=23, 74%) were exploratory but those that evaluated interventions (n=8, 26%) often did so within underserved populations (n=6). A majority of studies (n=30, 97%) did not specify their behaviours consistent with guidelines from behavioural scientists. The most used approaches were social cognitive theory (n=8, 26%), the theory of planned behaviour (n=6, 19%) and the theoretical domains framework (n=5, 16%). CONCLUSIONS: A range of behavioural approaches have been applied to recruitment and retention to trials. The multitude of recruitment research here is consistent with trials research generally and emphasises the need for research into retention. Authors report target behaviours minimally, which is not conducive to replication. Further research should build on lessons here, such as clearly specifying behaviours. Increased methodological rigour and transparency will lead to robust evidence bases and less research waste in poor recruitment and retention. Overall, trials informed by behavioural approaches promises to be efficient and more participant focused.

Fatty infiltration of the cervical multifidus musculature and their clinical correlates in spondylotic myelopathy.

Cervical spondylotic myelopathy (CSM) is among the most common spinal cord disorders of the elderly. Muscle fat infiltration (MFI), a potential pathological sign of muscle adiposity, may contribute to or be associated with pain/disability/impairments in patients with CSM. We examined the relationship between MFI and CSM's clinical manifestations by enrolling nine CSM patients and five aged-matched controls to undergo MRI imaging of the cervical spine with MFI. A blinded investigator calculated MFI for each of the bilateral multifidii muscles from C3 to C7 on the MRI images. Nurick scores, Neck Disability Index, and modified Japanese Orthopedic Association scores were collected for all patients. CSM patients and controls were equivalent with respect to age, height, weight, gender, race, smoking status, and employment status. MFI was higher in patients with CSM than in controls (31.7% v. 24.6%, respectively, p = 0.0178). Higher MFI was associated with increased disability on the Nurick scale (p = 0.0371). MJOA scores correlated linearly with MFI (R = 0.542, p = 0.0453), but not NDI (p = 0.3125). Increased MFI of the multifidus muscles is associated with cervical myelopathy and a clinically significant decline in sensorimotor function as measured by mJOA and Nurick scores. Spinal injury in CSM may lead to secondary muscle loss and muscle fat infiltration.