Initial workshop
Following initial discussions within the UKCRC Registered Clinical Trials Unit (CTU) Network about the problem of managing participation changes in clinical trials, a workshop was held in October 2019, in-person at the Institute of Clinical Trials and Methodology, University College London. In line with Network policy, each of the UKCRC Registered CTUs was invited to identify one representative to attend. Around 40 people attended the workshop to represent various roles and disciplines, including in statistics, data management, trial management, quality assurance, and CTU leadership roles.
The workshop agenda included introductory presentations exploring challenges currently experienced with managing participation changes in trials. Attendees were formed into small, multidisciplinary groups and asked to participate in a ‘structured brainstorm’ exercise. This involved discussing the question ‘how should withdrawal and loss to follow-up ideally be handled in ongoing trials’, in the context of six different areas: protocols, patient information, site training, further data processing, reporting requests [to CTUs] and trial reporting.
Attendees were asked to consider barriers and facilitators to their suggestions. Attendees were then shown additional suggestions developed by a working group at the Clinical Trials Research Unit (CTRU), University of Leeds.
In the second half of the workshop, attendees were asked to join new groups to discuss whichever of the six areas they were most interested to focus on. In these new groups, attendees were asked to review and refine the suggestions made so far, for example to combine points made and suggest wording for possible guiding principles. Notes from all discussions during the day were retained.
Further drafting of principles
Following the workshop, attendees were invited to participate in remotely-working ‘writing groups’ to further develop the draft principles within each of the same areas mentioned above. There was additionally a writing group for ‘overarching’ issues, the need for which had been identified at the workshop. Each group had one or two leads to coordinate the work, who would later form the project steering group.
Each writing group was asked to further refine the draft principles until they were ready for wider review (see example collaborative worksheet here). Groups were given guidance to aim for principles that were simple, broad, clearly expressed and specific to the topic area. They were asked to add a justification or explanation for each proposed principle, to enable anyone reading to understand to rationale. Groups were provided with a copy of the relevant notes from the workshop, and a list of discussion points relevant to each topic area. During this and subsequent phases of the project, we aimed for an inclusive approach, incorporating all new ideas as long as they were within scope. Once this stage was complete, the output from all the groups was brought together and members of all groups were asked to review the combined document.
Following further review and discussion across members of the writing groups, the existing content was formed into a single document listing the draft principles, each with a short explanation. This was shared with the whole PeRSEVERE collaborative group (i.e. everyone involved in the initial workshop, plus others who had not been able to attend that as they were not members of a UKCRC Registered CTU) in June 2020 for further feedback.
Feedback was logged in a standardised format and categorised based on its implications, including whether the feedback was suggesting a change and if so, the magnitude of the suggested change. Project leads were asked to respond to each point of feedback, with the PeRSEVERE project lead providing a second opinion where required and a suggested response where the feedback did not apply to a single draft principle.
The PeRSEVERE steering group agreed a general approach to handling feedback. All feedback and the proposed responses were made available to the PeRSEVERE steering group members.
In response to the feedback, a new draft of the principles document was created in August 2020. Following a steering group decision that the wording of the principles and accompanying explanations should be accessible to as many people as possible, this draft incorporated a patient contributor’s suggestions for simplified wording. The new draft was then turned into a ‘principles and explanation’ document in early 2021.
Further consultation
Following this initial work, there were 16 draft principles which we included in a public consultation, which generated further feedback to inform our final PeRSEVERE principles. The results of the public consultation will be reported in a journal article in due course.
Throughout the process of developing our principles, we have been guided by the high-level principles of ethical research conduct (including good clinical practice), our knowledge and understanding of existing clinical research regulations and guidance, and our collective experience of designing, running, analysing, reporting on and participating in clinical trials and other research.