Funding, protocol development and statistical planning

Research grant applications:

• Consider how to ensure there is adequate resource to support all study follow-up activity, including for participants whose participation changes during their time on study, and those who ‘complete’ all aspects of participation.
  

Protocol development:

• Protocols should retain the standard confirmation that participants have the right to withdraw their consent at any time.
• Protocol content should be written with an understanding that participation changes can take many forms. Use language to convey this complexity.
• All members of the study team can make important contributions to the protocol. For agreeing content about participation changes, there may be particularly important roles for statisticians and patient contributors.
• Consider presenting content about broad sorts of participation change in different sections.
• Consider referencing the PeRSEVERE principles and related guidance in the protocol, if these guide your study’s approaches.
• Consider using the protocol to emphasise some of the positions given in the PeRSEVERE principles, about how participation changes should be managed in the study.
• The protocol should explain what needs to happen when a participant says they want to stop or reduce their participation in the study.
• The protocol should include instructions for study staff in case they lose contact with participants.
• The protocol should be clear about any data collection that needs to continue in all cases.
• Options for reduced or alternative follow-up schedules or methods should be referenced, with instructions for how and when to broach them with participants.
• The protocol should contain any definitions of study-specific participation changes that are anticipated.
• The protocol could include guidance about what should happen if a participant wants to increase their level of involvement after having previously reduced it (especially if this is expected to happen relatively frequently, for any reason).
• Participating study sites might be encouraged to contact the clinical trials unit/research organisation to discuss the best action to take if any particularly complex or challenging situations arise.

Statistical analysis plans (SAPs):

• Given the breadth of existing guidance around content of SAPs, we have not given detailed recommendations within the PeRSEVERE guidance.
• However, we suggest that, as with other study documents, the language and terminology used in SAPs reflects the complexity of participation changes.
• If it has been agreed that participants who want to stop taking part can continue to contribute with less commitment via alternative follow-up schedules or methods, then the SAP could cover any implications for how the study outcome data will be analysed (i.e. if some data was collected in different ways).