Informing efficient randomised controlled trials: exploration of challenges in developing progression criteria for internal pilot studies

Abstract

ObjectivesDesigning studies with an internal pilot phase may optimise the use of pilot work to inform more efficient randomised controlled trials (RCTs). Careful selection of preagreed decision or ‘progression’ criteria at the juncture between the internal pilot and main trial phases provides a valuable opportunity to evaluate the likely success of the main trial and optimise its design or, if necessary, to make the decision not to proceed with the main trial. Guidance on the appropriate selection and application of progression criteria is, however, lacking. This paper outlines the key issues to consider in the optimal development and review of operational progression criteria for RCTs with an internal pilot phase.DesignA structured literature review and exploration of stakeholders' opinions at a Medical Research Council (MRC) Hubs for Trials Methodology Research workshop. Key stakeholders included triallists, methodologists, statisticians and funders.ResultsThere is considerable variation in the use of progression criteria for RCTs with an internal pilot phase, although 3 common issues predominate: trial recruitment, protocol adherence and outcome data. Detailed and systematic reporting around the decision-making process for stopping, amending or proceeding to a main trial is uncommon, which may hamper understanding in the research community about the appropriate and optimal use of RCTs with an internal pilot phase. 10 top tips for the development, use and reporting of progression criteria for internal pilot studies are presented.ConclusionsSystematic and transparent reporting of the design, results and evaluation of internal pilot trials in the literature should be encouraged in order to facilitate understanding in the research community and to inform future trials.

Nutrimetabolomics: An Integrative Action for Metabolomic Analyses in Human Nutritional Studies

“…Moreover, they help identify challenges in implementing a full‐scale trial to evaluate food matrix issues or to ascertain the dose or quantity of food to be consumed. Further, pilot studies form the basis of power calculations for subsequent controlled studies …”

A review of current practice in the design and assessment of internal pilots in UK NIHR clinical trials

“…Recommendations are made in the literature for developing these criteria including: basing recruitment targets on rates per centre per unit time, as opposed to an overall target number at a set time point, to account for unpredictability in site openings; inclusion of intervention adherence and cross-over; event rates; and review of missing data in terms of primary and secondary outcomes. Inclusion of both the funders and Trial Steering Committee (TSC) in the internal pilot review process is recommended [4]. …”

“…In terms of choosing the pilot sites, it is advised that these must be representative of the sites to be included in the main trial [4, 5]. The protocol should detail the timing of the internal pilot analysis and outline the progression criteria [2, 4, 5].…”

“…The protocol should detail the timing of the internal pilot analysis and outline the progression criteria [2, 4, 5]. …”

“…Little is known, however, about internal pilot trials in practice [4] and few empirical studies are undertaken yet they are widely recommended by funding bodies. The aim of this study was to provide an insight into current practice regarding internal pilots in clinical trials, specifically the design and review process, by assessing a cohort of studies funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme.…”