Standard Operating Procedures

Acknowledge that there may be ‘levels’ of participation, with participants taking part in all, some, few or no aspects of the trial depending on how their participation has changed.

Participation can also change without reducing, e.g. change in nature (such as a change in mode of follow-up) or increase (after having previously reduced).

Use language and terminology accordingly, recognising the complexity and communicating how participation has changed in each case. The general expectation should be that the nature and extent of participation changes is based on informed and freely-given decisions by participants. 

Decisions to make for each trial might include:

• Whether aspects of participation will be formally organised into tiers for practical reasons (see Protocol Development).
• What level of flexibility may be acceptable, from a trial integrity point of view, regarding what the protocol requires participants to do (e.g. in follow-up schedules – see principle D1). Alternatively, it may be important to specify any limitations on how participation could change. Trial teams should decide to what extent any flexibility (or lack thereof) needs to be communicated to participants and/or trial site staff.
• Whether there may be any alternative follow-up or data collection mechanisms or schedules (see principle D1), available to offer to participants who are struggling to stick to the default mechanism/schedule.
  • Examples may include follow-up by a different mode (e.g. phone calls instead of in-person visits) or data collection from a different source (e.g. using routinely-collected healthcare data instead of trial-specific data collection).
  • The alternative follow-up options may not need to be communicated to participants up front, and it may even be unhelpful to do this (see Informing Potential Participants).
  • Alternative arrangements should focus on collection of data required for the primary outcome measure and any other key outcome measures.
  • Teams should consider whether these alternatives, if they are less burdensome for all involved, should in fact be the default follow-up method for the trial.
  • If it is agreed that alternative follow-up options are not needed or useful, this decision could also be documented and explained within the trial master file. This might be the right approach where alternatives are not feasible, or where they might impair rather than help the trial achieve its research objectives.

• Trial teams should decide how they will manage loss of contact between participants and trial staff (see principle O4). This includes trial-specific instructions for trying to re-gain contact and when to stop trying. Teams should consider whether any methods to try to re-gain contact or collect further data may be considered intrusive by participants and should therefore only be done with participants’ consent. The general aim should be to reduce as far as possible the potential effects of loss of contact on the robustness of each trial’s results. The likelihood of many participants losing contact with the trial should be assessed in the pre-trial risk assessment.  
• Teams should consider if there are any trial-specific considerations affecting the general principle that data already collected is retained. This may include where it is considered fair to give participants a period to change their mind about providing data (as is done in some qualitative, interview-based research). Complexities around informed consent may also apply, e.g. use of a deferred consent model, or issues to do with loss of capacity to consent.
• Whether there may be any trial-specific aspects to which a ‘presumed ongoing consent’ approach to consent could be applied, i.e. where participants can say they want those aspects to stop, but the activities will otherwise continue unless and until participants do say that. Any such consent approaches must meet the conditions set out in the PeRSEVERE principles (especially principle O5):
  • The participation aspects affected must be low impact on participants (in terms of safety, time or emotional burden or anything else) and must be necessary.
  • The consent approach must be made clear to participants in advance.
  • It must be clear for participants how to say that they want the activity to stop.
  • Trial staff must make reasonable efforts to find out participants’ wishes about the different aspects of participation, when participants say they want to stop or reduce their participation.
  • If there is a suitable mechanism, participants should be reminded of what trial activity is still ongoing (if any) after they change their participation.
  • Any trial activity continuing on the basis of this approach must still be in line with the consent previously given.
  • Each case should nonetheless be reviewed on its own rather than applying a blanket rule. This includes allowing a route for the activity to stop if there is any doubt about the appropriateness of continuing (e.g. because of changes in a participant’s health, personal circumstances or capacity to consent).

• Any trial-specific processes in place to help record and maintain information about participants’ contact details and preferences for contact about the trial (e.g. for trial updates and the overall trial results). This includes checking if participants’ preferences change when they stop or reduce their participation (see Patient Information, Participant Communication and Consent).
  • Trial teams should decide their approach to sharing information about the trial (such as the trial’s results) with participants’ relatives or carers in the event the participant loses capacity to consent or dies while the trial is ongoing. The best approach will depend on the trial and should be decided with the help of the trial’s patient contributors.
• Whether any specific features of the trial might make handling participation changes more difficult. For example, in international trials different rules around clinical research or data protection may apply. There may be other specific issues  highlighted through the trial risk assessment.

This can include:

• Participants’ right to withdraw their consent at any time, without having to give a reason (unless they want to) and without their standard of care being affected.
• Recommended action for participants to take if they decide they want to stop or reduce their participation.
• Limitations on stopping or undoing any aspects of participation.
• Any aspects of participation that would continue until the participant explicitly says they want it to stop (see above for more on ‘presumed ongoing consent’ approaches).
• Where appropriate, the possibility of aspects of participation being stopped by someone else.
• The value to the trial of collecting as much of the planned data as possible (see principle O3).

Steps to follow can include:

• An expectation for CTU staff to discuss with trial site staff (where applicable) to establish exactly how the participant wants their participation to change, and their preferences for further contact about the trial. This process may include reminding trial site staff about what options are available to the participant.
  • Available options could routinely include consideration of whether transferring the participants’ care to a different trial site could allow the participant to continue taking part in the trial, if they want to and subject to the participant’s and other site’s agreement to the transfer.
• What level of evidence would be expected to be available – for example, in participants’ medical notes – to document a participant’s wish to stop all aspects of participation (including ‘active’ and ‘passive’ aspects).
• Ensuring a clear record of the participant’s wishes are conveyed to the CTU.
• Ensuring the participants’ wishes are recorded in the trial database and reported in line with the CONSORT statement and PeRSEVERE principle R2.
• Ensuring all steps are taken to carry out participants’ wishes. For example, if the participant does not want to complete any more trial questionnaires, preventing all further requests for questionnaires to be completed.
• If any aspects of participation are affected by ‘presumed ongoing consent’ approaches mentioned above, ensuring these are implemented in a consistent and fair manner and not applied in a blanket fashion.
• Carrying out any participant communications planned around the time of participation ending, such as an end of participation information sheet.
• Any expectations around monitoring of participation changes, both at trial-wide level and review of individual cases (see principle M2).

See Resources for template checklists to use when managing individual participation changes.

• SOPs could also explain any general exemptions to the data retention principle, for example if a participant’s original informed consent is called into question.
• Standard processes could include how to consider individual cases where it is requested or proposed that trial data be deleted. For example, who would need to be informed of such cases, and who would ultimately decide what should happen to the data, including the relevant Data Protection Officer(s) if required by local policies.
• If there is an expectation that retained data will be de-identified or otherwise have its identifiability reduced, steps for doing this could be explained.

For example, if data exists but only in confidential medical notes that would need to be accessed by trial staff based on participant consent, then this may not be so straightforward.

In that case, trial teams could in theory decide to apply a ‘presumed ongoing consent’ approach (see above), meaning that that accessing of confidential medical notes would continue until participants say they want it to stop. This could only be for the purpose of collecting data generated until the point the participant said they wanted data collection to stop.

However, in this scenario, it might be challenging to meet the conditions for ‘presumed ongoing consent’ to be done in a fair and transparent way, as mentioned above and in PeRSEVERE principle O5.

Where it is agreed to make such contact with those who have stopped, SOPs could set out the process to go through to share this information. This could include specific approval from a Research Ethics Committee (REC) to share the information, particularly if this would involve contacting participants who had said they did not want any further contact about the trial.