Do investigator meetings improve recruitment rates in clinical trials? A retrospective before-and-after study of data from nine multi-centre clinical trials

© 2020 The Author(s). Background: Poor recruitment in clinical trials is well-documented. In large, multi-centre trials, communication between the coordinating centre and trial sites is essential. A commonly used communication tool is the hosting of an investigator/collaborator meeting, which offers an opportunity for sites to re-train and receive trial updates, learn from each other, share best practice and troubleshoot issues. Anecdotally, there is a perception that recruitment rates may increase after holding such a meeting. The aim of this before-and-after study was to examine any changes in recruitment after an investigator meeting. Methods: We conducted a retrospective study of nine trials at the Nottingham Clinical Trials Unit (NCTU) that were open to recruitment between 2014 and 2018. In the 8 weeks prior to the date of the investigator meeting, 82 sites (across nine trials) were open to recruitment; 60 of which attended the meeting, 22 who did not. Using meeting attendance data available in Trial Master Files (TMF) and recruitment data from randomisation datasets, we examined recruitment rates in the 8 weeks prior to and following the date of the investigator meeting. Results: For the 82 sites included, 284 participants were recruited in the 8 weeks prior to the meeting, with a further 300 participants recruited in the 8 weeks post meeting. This gives a mean change in weekly recruitment of 0.073 (- 0.129, 0.275) per site, demonstrating no statistically significant increase in recruitment after the investigator meeting. For the 60 attending sites, recruitment increased from 254 participants prior to the meeting to 271 post meeting, giving a 0.100 (- 0.160, 0.360) mean change in weekly recruitment per site, providing no evidence that recruitment rates increase following an investigator meeting. Conclusion: There is no statistical evidence to conclude that holding an investigator meeting increases recruitment in the 8 weeks following the meeting. Thus, if the meeting has been held in the belief that it will have a positive impact upon recruitment, trialists may wish to consider other evidence-based strategies known to increase recruitment rates. However, since there are a variety of reasons why an investigator meeting may be held, trialists should continue to consider this as a communication strategy with sites

Value and engagement : what can clinical trials learn from techniques used in not-for-profit marketing?

No funding has been received for this work.Peer reviewedPublisher PD

Value and engagement: what can clinical trials learn from techniques used in not-for-profit marketing?

Marketing is a core business function in commercial companies but is also frequently used by not-for-profit organisations. Marketing focuses on understanding what people value to make choices about engaging with a product or service: a concept also key to understanding why people may choose to engage with a clinical trial. Understanding the needs and values of stakeholders, whether they are participants, staff at recruiting sites or policy-makers, is critical for a clinical trial to be a success. As many trials fail to recruit and retain participants, perhaps it’s time for us to consider approaches from other disciplines? Though clinical trial teams may consider evidence- and non-evidence-based recruitment and retention strategies, this is rarely done in a systematic, streamlined way and is often in response to challenges once the trial has started. In this short commentary, we argue the need for a formal marketing approach to be applied to clinical trials, from the outset, as a potential prevention to recruitment and retention problems

Recruitment of older adults to three preventative lifestyle improvement studies

YesBackground: Recruiting isolated older adults to clinical trials is complex, time-consuming and difficult. Previous studies have suggested querying existing databases to identify appropriate potential participants. We aim to compare recruitment techniques (general practitioner (GP) mail-outs, community engagement and clinician referrals) used in three randomised controlled trial (RCT) studies assessing the feasibility or effectiveness of two preventative interventions in isolated older adults (the Lifestyle Matters and Putting Life In Years interventions). Methods: During the three studies (the Lifestyle Matters feasibility study, the Lifestyle Matters RCT, the Putting Life In Years RCT) data were collected about how participants were recruited. The number of letters sent by GP surgeries for each study was recorded. In the Lifestyle Matters RCT, we qualitatively interviewed participants and intervention facilitators at 6 months post randomisation to seek their thoughts on the recruitment process. Results: Referrals were planned to be the main source of recruitment in the Lifestyle Matters feasibility study, but due to a lack of engagement from district nurses, community engagement was the main source of recruitment. District nurse referrals and community engagement were also utilised in the Lifestyle Matters and Putting Life In Years RCTs; both mechanisms yielded few participants. GP mail-outs were the main source of recruitment in both the RCTs, but of those contacted, recruiting yield was low (< 3%). Facilitators of the Lifestyle Matters intervention questioned whether the most appropriate individuals had been recruited. Participants recommended that direct contact with health professionals would be the most beneficial way to recruit. Conclusions: Recruitment to the Lifestyle Matters RCT did not mirror recruitment to the feasibility study of the same intervention. Direct district nurse referrals were not effective at recruiting participants. The majority of participants were recruited via GP mail-outs, which may have led to isolated individuals not being recruited to the trials. Further research is required into alternative recruitment techniques, including respondent-driven sampling plus mechanisms which will promote health care professionals to recruit vulnerable populations to research.The Lifestyle Matters RCT was funded by the Medical Research Council (grant number G1001406); Sheffield Health and Social Research Consortium; National Institute for Health Research Public Health Research programme (project number 09/ 3004/01

The implementation of Journeying through Dementia : strategies to run a successful pragmatic multicenter trial of a complex intervention

Objective A key challenge in delivering pragmatic trials of complex interventions is effective implementation within the study period and beyond. We describe a trial of an intervention to improve quality of life in mild dementia (Journeying through Dementia), describe some of the challenges raised in terms of implementation, and illustrate the methods used to ensure effective implementation. Method The intervention was delivered by staff within local services and supervised by more experienced clinicians within those services in order to test the intervention in real-world settings and establish the potential for future embedding into practice. Researchers delivered training sessions for all facilitators and supervisors, met at regular intervals with intervention supervisors, and provided feedback on summaries of intervention sessions created by facilitators. We conducted a thematic analysis of the content of meetings and written correspondence between the researchers and intervention supervisors regarding implementation issues. Results Key themes relating to difficulties with implementation were: staff absences and staff leaving posts; participant lack of engagement with intervention; difficulties with delivery of supervision; difficult group dynamics; lack of time to deliver the intervention; and lack of adherence to the intervention and its ethos. Conclusion We provide guidance for researchers involved in the trialing of other complex interventions in how these challenges might be overcome. These include: recruiting additional staff to deliver the intervention; having clear protocols in place for managing staff absences; using supervision to problem solve participant attendance at intervention sessions and difficult group dynamics; monitoring staff engagement in supervision and addressing problems with engagement with staff and managers when this occurs; giving staff ring-fenced time to deliver the intervention and engage in supervision; and regular monitoring and feedback in relation to the content of the intervention to ensure that it is consistent with ethos and content of the intervention manual

Journeying through dementia randomised controlled trial of a psychosocial intervention for people living with early dementia: embedded qualitative study with participants, carers and interventionists

Objective: To identify the barriers and facilitators to the implementation of a complex psychosocial intervention though a study exploring the experiences of participants, carers and interventionists during a trial. Methods: Individual semi-structured interviews were conducted with participants, their carers, and interventionists from a sample of recruiting sites that took part in the Journeying through Dementia randomized controlled trial (RCT). Interview data were transcribed and analysed using framework analysis. Co-researcher data analysis workshops were also conducted to explore researcher interpretations of the data through the lens of those with lived experience of dementia. Triangulation enabled comparison of findings from the interviews with findings from the co-researcher workshops. Results: Three main themes emerged from the interview data: being prepared; intervention engagement; and participation and outcomes from engagement. From these themes, a number of factors that can moderate delivery and receipt of the intervention as intended were identified. These were context and environment; readiness, training, skills and competencies of the workforce; identifying meaningful participation and relationships. Conclusion: This study highlighted that the observed benefit of the intervention was nuanced for each individual. Mechanisms of change were influenced by a range of individual, social and contextual factors. Future research should therefore consider how best to identify and measure the multifaceted interplay of mechanisms of change in complex interventions. Trial Registration: ISRCTN17993825

Embedding patient and public involvement in dementia research: Reflections from experiences during the ‘Journeying through Dementia’ randomised controlled trial

Background: The involvement of people with a diagnosis of dementia in patient and public involvement and engagement (PPIE) in research is an emerging field in the delivery of studies. Researchers need to understand and use the learning derived from various projects so that this growing body of knowledge can be applied in future research. Objective: To embed PPIE throughout a randomised controlled trial of a psychosocial intervention called Journeying through Dementia. We identify and discuss the approaches to involvement that worked well and those where improvements were indicated. Design: The Guidance for Reporting Involvement of Patients and the Public Short Form (GRIPP2-SF) is used to describe and critically appraise the approaches taken and the impact of PPIE involvement upon study processes, the study team and those people with dementia and their supporters who acted as advisors. Findings: The involvement of people with a diagnosis of dementia and supporters as study advisors improved the accessibility and relevance of the research for people living with dementia. It also highlighted issues that researchers may have otherwise overlooked. Successful engagement of people with dementia and their supporters in the study was associated with staff skills and particularly use of techniques to scaffold meaningful involvement, as well as participants’ memory and cognitive capacity. However, embedding robust and meaningful involvement processes required significant time and resources. Discussion: We propose that certain research processes need to be adapted to be accessible and appropriate for people living with dementia. Recruitment of PPIE advisors needs to reflect population diversity. There also needs to be greater parity of voice between people with lived experience of dementia and researchers. These steps will increase the impact of PPIE in research and improve the experience for those who volunteer to be PPIE advisors

A randomised feasibility trial comparing needle fasciotomy with limited fasciectomy treatment for Dupuytren’s contractures

© 2020 The Author(s). Purpose: The purpose of this study is to assess the feasibility of conducting a large, multicentre randomised controlled trial (RCT) comparing needle fasciotomy with limited fasciectomy for treatment of Dupuytren's contractures. Design: The design of this study is a parallel, two-arm, multicentre, randomised feasibility trial with embedded QuinteT Recruitment Intervention. Participants: Patients aged 18 years or over who were referred from primary to secondary care for treatment of a hand with Dupuytren's contractures of one or more fingers of more than 30° at the metacarpophalangeal (MCP) and/or proximal interphalangeal (PIP) joints and well-defined cord(s). Patients were excluded if they had undergone previous Dupuytren's contracture surgery on the same hand. Methods: Potential participants were screened for eligibility. Recruited participants randomised (1:1) to treatment with either needle fasciotomy or limited fasciectomy and followed-up for up to 6 months after treatment. Data on recruitment rates, completion of follow-up, and procedure costs were collected. Four patient reported outcome measures (PROMs) and objective outcome measures were collected before intervention and 6 weeks and 6 months afterwards. Results: One hundred and fifty-three of 267 (57%) primary-care referrals for Dupuytren's contractures met the eligibility criteria for the study. Seventy-one of the 153 (46%) agreed to participate and were randomly allocated to treatment with needle fasciotomy or limited fasciectomy. Sixty-seven of these underwent their allocated treatment, two were crossovers from limited fasciectomy to needle fasciotomy, and two (both allocated limited fasciectomy) received no treatment. Fifty-nine participants (85%) completed 6-month follow-up PROMs. Participants felt the MYMOP, PEM and URAM PROMs allowed them to better describe how their treatment affected their hand function than the DASH PROM. The estimated costs of limited fasciectomy (in an operating theatre) and needle fasciotomy (in a clinic room) were £777 and £111 respectively. Conclusion: A large RCT comparing treatment of Dupuytren's contractures by needle fasciotomy and limited fasciectomy is feasible. Data from this study will help determine the number of sites and duration of recruitment required to complete an adequately powered RCT and will assist the selection of PROMs in future studies on the treatment of Dupuytren's contractures. (Level 1 feasibility study)

Precision computerised cognitive behavioural therapy (cCBT) for adolescents with depression: a pilot and feasibility randomised controlled trial protocol for SPARX-UK

Background A serious game called SPARX (Smart, Positive, Active, Realistic, X-factor thoughts), originally developed in New Zealand and incorporating cognitive behavioural therapy (CBT) principles, has been shown to help reduce symptoms of depression and anxiety in adolescents with mild to moderate depression in studies undertaken in Australasia. However, SPARX has never been trialled in the United Kingdom (UK), and there have been issues relating to low engagement when it has been used in a real-world context. Aims To conduct the first pilot and feasibility randomised controlled trial (RCT) in England to explore the use of SPARX in different settings. The trial will explore whether SPARX supported by an e-coach (assistant psychologists) improves adherence and engagement compared with self-directed (i.e. self-help) use. The trial results will be used to inform the optimal mode of delivery (SPARX supported vs. SPARX self-directed), to calculate an appropriate sample size for a full RCT, and to decide which setting is most suitable. Methods Following consultation with young people to ensure study suitability/appropriateness, a total of 120 adolescents (11–19 years) will be recruited for this three-arm study. Adolescents recruited for the study across England will be randomised to receive either SPARX with human support (from an e-coach), self-directed SPARX, or a waitlist control group. Assessments will be conducted online at baseline, week 4, and 8–10-week post-randomisation. The assessments will include measures which capture demographic, depression (Patient Health Questionnaire modified for adolescents [PHQ-A]) and anxiety (Revised Child Anxiety and Depression Scale [RCADS]) symptomatology, and health-related quality-of-life data (EQ-5D-Y and proxy version). Analyses will be primarily descriptive. Qualitative interviews will be undertaken with a proportion of the participants and clinical staff as part of a process evaluation, and the qualitative data gathered will be thematically analysed. Finally, feasibility data will be collected on recruitment details, overall study uptake and engagement with SPARX, participant retention, and youth-reported acceptability of the intervention. Discussion The findings will inform the design of a future definitive RCT of SPARX in the UK. If the subsequent definitive RCT demonstrates that SPARX is effective, then an online serious game utilising CBT principles ultimately has the potential to improve the provision of care within the UK’s health services if delivered en masse

Eicosapentaenoic acid and aspirin, alone and in combination, for the prevention of colorectal adenomas (seAFOod Polyp Prevention trial): a multicentre, randomised, double-blind, placebo-controlled, 2 × 2 factorial trial

YesBackground: The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) and aspirin both have proof of concept for colorectal cancer chemoprevention, aligned with an excellent safety profile. Therefore, we aimed to test the efficacy of EPA and aspirin, alone and in combination and compared with a placebo, in individuals with sporadic colorectal neoplasia detected at colonoscopy. Methods: In a multicentre, randomised, double-blind, placebo-controlled, 2 × 2 factorial trial, patients aged 55–73 years who were identified during colonoscopy as being at high risk in the English Bowel Cancer Screening Programme (BCSP; ≥3 adenomas if at least one was ≥10 mm in diameter or ≥5 adenomas if these were <10 mm in diameter) were recruited from 53 BCSP endoscopy units in England, UK. Patients were randomly allocated (1:1:1:1) using a secure web-based server to receive 2 g EPA-free fatty acid (FFA) per day (either as the FFA or triglyceride), 300 mg aspirin per day, both treatments in combination, or placebo for 12 months using random permuted blocks of randomly varying size, and stratified by BCSP site. Research staff and participants were masked to group assignment. The primary endpoint was the adenoma detection rate (ADR; the proportion of participants with any adenoma) at 1 year surveillance colonoscopy analysed in all participants with observable follow-up data using a so-called at-the-margins approach, adjusted for BCSP site and repeat endoscopy at baseline. The safety population included all participants who received at least one dose of study drug. The trial is registered with the International Standard Randomised Controlled Trials Number registry, number ISRCTN05926847. Findings: Between Nov 11, 2011, and June 10, 2016, 709 participants were randomly assigned to four treatment groups (176 to placebo, 179 to EPA, 177 to aspirin, and 177 to EPA plus aspirin). Adenoma outcome data were available for 163 (93%) patients in the placebo group, 153 (85%) in the EPA group, 163 (92%) in the aspirin group, and 161 (91%) in the EPA plus aspirin group. The ADR was 61% (100 of 163) in the placebo group, 63% (97 of 153) in the EPA group, 61% (100 of 163) in the aspirin group, and 61% (98 of 161) in the EPA plus aspirin group, with no evidence of any effect for EPA (risk ratio [RR] 0·98, 95% CI 0·87 to 1·12; risk difference –0·9%, –8·8 to 6·9; p=0·81) or aspirin (RR 0·99 (0·87 to 1·12; risk difference –0·6%, –8·5 to 7·2; p=0·88). EPA and aspirin were well tolerated (78 [44%] of 176 had ≥1 adverse event in the placebo group compared with 82 [46%] in the EPA group, 68 [39%] in the aspirin group, and 76 [45%] in the EPA plus aspirin group), although the number of gastrointestinal adverse events was increased in the EPA alone group at 146 events (compared with 85 in the placebo group, 86 in the aspirin group, and 68 in the aspirin plus placebo group). Six upper-gastrointestinal bleeding events were reported across the treatment groups (two in the EPA group, three in the aspirin group, and one in the placebo group). Interpretation Neither EPA nor aspirin treatment were associated with a reduction in the proportion of patients with at least one colorectal adenoma. Further research is needed regarding the effect on colorectal adenoma number according to adenoma type and location. Optimal use of EPA and aspirin might need a precision medicine approach to adenoma recurrence.Efficacy and Mechanism Evaluation Programme, a UK Medical Research Council and National Institute for Health Research partnership.Research Development Fund Publication Prize Award winner, November 2018