The role of progression criteria in the design, conduct, analysis and reporting of external randomised pilot trials
Keywords: pilot
trialmethodology
clinicaltrial
feasibility

External randomised pilot trials aim to assess whether a future definitive Randomised Controlled Trial (RCT) is feasible. Prespecified progression criteria help guide the interpretation of pilot trial findings to decide whether, and how, a definitive RCT should be conducted. Transparent feasibility assessment is crucial to ensure that pilot trials do not progress to definitive RCTs inappropriately. The research presented in this thesis examined the development, assessment and reporting of progression criteria throughout different stages of external randomised pilot trials.
As part of this DPhil I conducted four distinct but complementary research studies: a methodological review of progression criteria reported in randomised pilot trial protocol and result publications (published between January 2018 and December 2019); a cross-sectional study of progression criteria proposed in external randomised pilot trial research funding applications submitted to NIHR Research for Patient Benefit (RfPB) (with a funding decision between July 2017 and July 2019); a qualitative research study of thirty-five semi-structured interviews with key stakeholders (between December 2020 and July 2021) to understand pilot trial team member experiences of developing and using progression criteria in practice; a web-based follow-up survey study (between January 2022 and February 2022) of corresponding authors of publications included in the methodological review to examine whether identified pilot trials met their progression criteria (if applicable), were considered feasible, and progressed to further research.
I found that progression criteria were not always prespecified in pilot trial funding applications or reported in pilot trial publications. Where specified, researchers rarely stated how they had developed progression criteria, what specific criteria or targets were based on, or who had decided on them. My qualitative study findings highlighted varied and inconsistent approaches to progression criteria development, and suggest that a lack of knowledge, time and resources can lead to challenges when developing progression criteria. My findings also highlighted limitations associated with trial feasibility assessment, including the potential for biased pilot trial progression criteria, uncertainty about how to account for qualitative research findings and contextual considerations, and inefficiencies associated with non-progression of pilot trials that researchers considered to be feasible. Taken together, these findings indicate that progression criteria for external pilot trials might not always provide a comprehensive assessment of trial feasibility.
To address the challenges identified, I developed a set of proposed recommendations for progression criteria to guide researchers when (1) designing, (2) conducting, (3) analysing and (4) reporting external randomised pilot trials. These recommendations were refined following input from key stakeholders at two consultation workshops held in July 2022. Further research is needed to evaluate whether these proposed recommendations should inform future development, or update, of established guidelines for the design, conduct, analysis and reporting of external randomised pilot trials.