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Abstract
Objectives Designing 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.
Design A 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.
Results There 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.
Conclusions Systematic 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.
- STATISTICS & RESEARCH METHODS
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Collaborators The authors would like to acknowledge contributions from the following specialists who attended and contributed to the Internal Pilot Trials specialist workshop supported by the Hubs for Trials Methodology Research in March 2014, and who thereby contributed to this paper: Natalie Blencowe, University of Bristol; Carol Bugge, University of Stirling; Michael Campbell, University of Sheffield; Michelle Collinson, University of Leeds; Cindy Cooper, University of Sheffield; Janet Darbyshire, Arthritis Research UK; Munya Dimairo, University of Sheffield; Caroline Doré, Medical Research Council Clinical Trials Unit, University College London; Sandra Eldridge, Centre for Primary Care and Public Health, Queen Mary University of London; Amanda Farrin, University of Leeds; Nadine Foster, Keele University; Simon Gilbody, University of York; Steve Goodacre, University of Sheffield; Lisa Hampson, Lancaster University; Angelos G Kolias, Cambridge Clinical Trials Unit and University of Cambridge; Sallie Lamb, University of Warwick, University of Oxford; Athene Lane, University of Bristol; Lisa Maguire, Queen's University Belfast; John Norrie, University of Aberdeen; Ruth Pickering, University of Southampton; Gillian Shorter, Ulster University and Australian National University; Shaun Treweek, University of Aberdeen, members of the Internal Pilot Trials Workshop supported by the Hubs for Trials Methodology Research.
Contributors KNLA, PRW, CG, EOF, CM, PD and JMB contributed to the study conception and research design. KNLA and JMB led on all aspects of workshop design and conduct and on drafting of the manuscript. KNLA, PRW, CG, EOF, CM, PD, HW and JMB each contributed to drafting of the manuscript. KNLA, JMB, CG, SGi, CD, CC and PD presented data at the workshop. All authors attended the workshop and participated in workshop discussions. They also contributed to analysis and interpretation of data and directly commented on, and contributed to, the manuscript. All authors have seen and given final approval of the version to be published.
Funding This work was supported by the Medical Research Council (MRC) Network of Hubs for Trials Methodology Research (MR/L004933/1- R41). This work was undertaken with the support of the MRC ConDuCT-II (Collaboration and innovation for Difficult and Complex randomised controlled Trials In Invasive procedures) Hub for Trials Methodology Research (MR/K025643/1) and the MRC North West Hub for Trials Methodology Research (MR/K025635/1).
Disclaimer The views expressed in this publication are those of the authors and not necessarily those of the Medical Research Council.
Competing interests All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/coi_disclosure.pdf and declare: SL is Chair of the National Institute for Health Research Health Technology Assessment Programme Clinical Evaluation and Trials Board. HW is Chair of the National Institute for Health Research Health Technology Assessment Programme Commissioning Board and Programme Director for the NIHR HTA Programme.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement No additional data are available.