Undertaking studies within a trial to evaluate recruitment and retention strategies for RCTs: lessons learnt from the PROMETHEUS research programme.

Background
Randomised controlled trials (‘trials’) are susceptible to poor participant recruitment and retention. Studies Within A Trial (SWATs) are the strongest methods for testing the effectiveness of strategies to improve recruitment and retention. However, relatively few of these have been conducted.
Aims
PROMoting THE USE of Studies Within A Trial (PROMETHEUS) aimed to facilitate at least 25 SWATs evaluating recruitment or retention strategies. We share our experience of delivering the PROMETHEUS programme, and the lessons learnt for undertaking randomised SWATs.
Design
A network of 10 Clinical Trials Units (CTUs) and one primary care research centre committed to conducting randomised controlled SWATs of recruitment and/or retention strategies was established. Promising recruitment and retention strategies were identified from various sources including Cochrane systematic reviews, the SWAT Repository, and existing prioritisation exercises, which were reviewed by patient and public (PPI) members to create an initial priority list of seven recruitment and eight retention interventions. Host trial teams could apply for funding and receive support from the PROMETHEUS team to undertake SWATs. We also tested the feasibility of undertaking coordinated SWATs, across multiple
host trials simultaneously.
Setting
CTU-based trials recruiting or following up participants in any setting in the UK were eligible.
Participants
CTU-based teams undertaking trials in any clinical context in the UK.
Interventions
Funding of up to £5,000 and support from the PROMETHEUS team to design, implement, and report SWATs.
Main outcome measures
Number of host trials funded.
Results
42 SWATs were funded (31 host trials), across 12 CTUs. The mean cost of a SWAT was £3,535. Twelve SWATs tested the same strategy across multiple host trials using a coordinated SWAT design, and four used a factorial design. Two recruitment and five retention strategies were evaluated in more than one host trial. PROMETHEUS will add 18% more SWATs to the Cochrane systematic review of recruitment strategies, and 79% more SWATs to the Cochrane review of retention
strategies. For retention, we found that pre-notifying participants by card, letter or email before sending questionnaires was effective, as was the use of pens, and sending personalised text messages to improve questionnaire response. We highlight key lessons learnt to guide others planning SWATs, including involving PPI partners; prioritising and selecting strategies to evaluate and elements to consider when designing a SWAT; obtaining governance approvals; implementing
SWATs, including individual and coordinated SWATs, and; reporting SWATs.
Limitations
The COVID-19 pandemic negatively impacted five SWATs, being either delayed (n=2) or prematurely terminated (n=3).
Conclusions
PROMETHEUS significantly increased the evidence base for recruitment and retention strategies. When provided with both funding and practical support, host trial teams successfully implemented SWATs.
Future research
Future research should identify and target gaps in the evidence base, including widening SWAT uptake, undertaking more complex SWATs, and translating SWAT evidence into practice.
Study registration
All SWATs had to be registered with the Northern Ireland Network for Trials Methodology Research SWAT Repository.
Funding details
This project was funded by the Medical Research Council (MR/R013748/1) and National Institute for Health Research as part of the MRC–NIHR Methodology Research programme.