Trial Forge Guidance 5: ethical considerations in randomised Studies Within A Trial (SWATs)

Background Randomised trials often struggle with recruitment, retention, and delays, impacting both finances and patient care. To improve trial processes, trialists can do Studies Within A Trial (SWATs) that compare trial process alternatives. Although SWATs are recognized by funders, there are differences in how they are implemented, such as different consent requirements in the UK and Ireland. This complicates SWAT conduct, raises ethical considerations, and highlights the need for standardised, ethical approaches to SWATs. The purpose of the current study was to devise guidance to address this. Methods We used existing systematic reviews, searched PubMed and the SWAT register, and contacted SWAT teams known to the authors to identify relevant randomised SWATs. We extracted information on any challenges in the SWAT approval process, as well as challenges implementing the SWAT. We held three consensus building forums, all including representatives from nine key stakeholder groups representing a broad range of roles in trials. We presented participants with two SWATs to start conversation on perceived ethical issues. Consensus building forums were recorded, transcribed, and analysed using NVivo, focusing on ethical principles, challenges, and solutions. Results We developed guidance on ethical considerations applicable to randomised SWATs. The guidelines cover all stages of a SWAT, from development and SWAT team selection to communication of results. Conclusions Studies Within a Trial are generally perceived to be low risk and low burden to participants. However, there are still variation in ethical standards applied to these studies by researchers, sponsors and ethics committees. In addition, SWATs are uniquely distinct from trials, presenting specific for their ethical conduct. These guidelines will be helpful to anyone planning or reviewing SWATs in understanding these differences and their ethical implications and provide a practical guide for the ethical conduct of SWATs.