Transitioning from Feasibility to Main trial: transparent Reporting of Modifications and Adaptations of Trial design Elements (TRANSFoRMATE)

Research question In studies determining the efficacy of complex interventions, where an external pilot or feasibility study precedes the definitive study and the outcome is “continue to main trial but modify protocol (feasible with modifications)”: • Which study design elements get modified, and to what extent, when progressing to the main trial? • What degree of modification is acceptable for the external pilot/feasibility findings to remain valid for the main phase?

Background Pilot and feasibility studies are essential in developing complex interventions, especially in preparing for larger randomized controlled trials (RCTs).

They help prevent resource wastage by avoiding investment in unviable full trials while offering valuable insights for refining interventions and trial designs.

However, there is a gap in understanding how these preliminary studies inform subsequent trials and lack of guidance on reporting modifications between pilot/feasibility and main trials.

Clearer specifications are needed on evaluating pilot/feasibility results and understanding how modifications affect the main study's design and success.

Concerns about the credibility of feasibility post-modifications may lead to research and funding inefficiencies, highlighting the urgency of addressing these gaps in current practices. Aims We will develop a tool for the systematic assessment and reporting of these modifications. Methods Workpackage 1a.

Systematic review.

We will examine a recent large representative sample of protocols of main trials of complex interventions which had a published preceding external randomised pilot/feasibility trial to record any protocol modification between the pilot/feasibility and the main trial. Workpackage 1b. Design of the Delphi study.

Findings from 1a will inform the development of questions and statements for inclusion in the Delphi study. Workpackage 2. Delphi study.

Through a Delphi process we will engage with diverse stakeholders to get consensus on what modifications are acceptable, who should be involved in the decisions on modifications, and what should be the format of the tool to report these modifications. Workpackage 3. Reporting tool.

We will develop a tool for reporting modifications and extent of modifications, who was responsible for evaluating the modification and potential consequences for the main trial design and conduct. The format of the tool will be informed by workpackage 2. We will adapt the reporting tool to make it understandable to participants, PPIE and members of the public.

Timelines for delivery 18 months Anticipated impact Researchers can use this reporting tool: a) in support of grant applications for the main study, b) for reporting the results of the pilot study, c) for recording what has been modified and reasons for modifications and d) to communicate changes to the protocol with PPIE members and to participants in both pilot/feasibility and main trial.

Dissemination Research outcomes will be disseminated through presentations at international conferences focused on trial methodology, as well as through publication in peer-reviewed journals.

We will share findings with the project Expert Advisory Group (EAG) and will solicit guidance from the EAG regarding the most effective strategies for disseminating the results. We will engage public members in presenting and developing blog posts for a wider audience.