Informing potential participants

Potential research participants must be made aware of their right to withdraw their informed consent at any time after having given it.

Trial staff must also be transparent with potential participants about the trial’s approaches to managing participation changes so that the individuals can take this information into account when deciding whether to take part in a clinical trial. This information can also inform decisions about their ongoing involvement if they do take part.

If some details of the approaches are not included in the pre-study information, it can be inappropriate (or even unethical or coercive) to mention them only later when a participant wants to stop taking part.

For this reason, some of the approaches we recommend (such as the ‘presumed ongoing consent’ approach*) can only be validly applied if they are mentioned up front.

Participants should not be surprised by any limitations on what they can stop or ‘undo’. Any such limitations must be made clear to potential participants before they agree to take part.

The practicalities around changing participation should also be clear – what participants can expect to happen if they stop or change their participation, and what might be expected of them at that time (if anything).

This collectively constitutes potentially quite a lot of information to convey to potential participants about participation changes. This has significant potential to be overwhelming or contribute to well acknowledged ‘information overload’ and over-long clinical trial information sheets.

Arguably, much of the detail about participation changing is not so relevant at the point when a patient is deciding to start participating and it might seem strange or unhelpful to give it too much emphasis then.

A possible solution is to ‘layer’ the information. This can be done in two complementary ways.

Firstly, layering of pre-trial information, with short-as-possible documents giving the key points that all potential participants need to know, and long-as-necessary detailed information available to those who want it (for example, online or on paper depending on patient preference).

Secondly, assuming participants are given information throughout their involvement in a trial (in line with the idea that consent should be ongoing), different sorts of information can be given different emphasis during the trial.

For example, at the start of the trial the most important thing might be to confirm that the participant can change their mind about taking part whenever they want.

At a later stage, should they be struggling to complete all trial activities, the information about participation changes becomes more relevant and can be highlighted. It may also be useful to consider what information the potential participant themselves is most interested to have.

More research is needed to define the optimal split of information across these different layers in the context of information about participation changes.

It would be valuable to agree template wording for information sheets that could be acceptable for participants, ethics committees (who need to review and approve written trial information for potential participants) and suitable for trialists’ needs. Use of graphics or visual aids could reduce the reliance on text.

It may also help avoid overwhelming participants to convey some points verbally as well as in writing (or potentially instead, though it may be important to always provide some of the points in writing). Trial staff training and experience and standardised processes can ensure the desired points are covered in discussions.

Trial staff should keep information balanced and calm, avoiding any risk of causing alarm. Others have suggested language emphasising ‘voluntariness’ and ‘encouragement’ over ‘requirement or expectation’ can reduce the risk of communications appearing coercive.

* This means participants’ consent to a particular trial activity is presumed to be ongoing if the participant has not said they want that activity to stop, as long as certain conditions are met. For more details, see PeRSEVERE principle O5.

Information for potential participants should be written with an understanding that participation changes can take many forms, rather than being a binary condition of participating/not, consenting/withdrawn (see principle O1).

Use language to convey this complexity. Suggestions for terminology to use are available in Resources.

When explaining about collecting as much as possible of the planned data, emphasise the main trial outcomes in particular. Make clear to potential participants what those are, how they are collected, when they are collected and how long they are collected for.

The point should also be made positively. Explain how it is good for the study to collect more of the planned data or put this in the context of valuing participants’ contributions, rather than referring to any potential negative impacts of missing data on trial results.

Others have suggested it could be useful to take time to discuss any concerns the patient may have about the data collection process.

The point about providing a reason or motivation for changing participation can make clear what sort of information might be useful.

This includes information to help trial statisticians assess whether the participation change has anything to do with the trial outcomes. Information on reasons for change can also inform the trial team about how they could improve the trial for participants.

Participants can therefore also be reassured that they would not need to provide lots of additional, potentially sensitive detail about why their participation was changing.

They should nonetheless be aware of the possibility that they may be asked if they would be happy to give a reason.

All these points must be made sensitively, using wording approved by a research ethics committee (REC).

Informing potential participants of these points gives them ‘balanced’ information (see principle D3) and allows them to make informed choices about stopping or changing their participation.

It is unethical to put pressure on participants to continue participating in a study, or to provide a reason for stopping.

However, it is also inappropriate to deny participants information about their choices, and information to guide those choices, if they may be keen to continue supporting the study as much as they can.

Participants should be reassured that whatever they decide is acceptable, and there are no ‘wrong’ decisions.

This does not mean they would have limitless options to change, as they would still need to participate in ways that are safe for them and help the trial meet its objectives.

Participants can be reassured that their choices would be made clear to them and that they would be offered help to understand their options and make the right choice for them.

This should include details of any particular action requested of participants, such as returning unused trial medication, providing trial outcome data, or attending a final trial clinic visit for safety monitoring or other reasons.

It should be clear that these requested actions are optional, or if they are more strongly encouraged, why that might be. Reasons for any requested actions should be made clear.

They can be advised to speak with their trial doctor or nurse (see principle D5 – encouraging dialogue) if they are finding participation difficult, in case something can be done to allow them to continue participating.

It should be obvious to participants how to get in contact with the relevant person, and they might be provided with more than one way to do this. It should be clear to participants why they might be advised to do this.

It may not be helpful to go into detail about the availability of reduced commitment options up front. Doing this might give a confusing message about what taking part in the study would involve or might encourage participants to opt immediately for the reduced option, therefore impairing the trial objectives.

It could nonetheless be sensible to mention, if there is more than one trial site and site transfers are allowed in the trial, that the participant could decide to move to a different trial site (subject to that site’s agreement). A link to further information (for example, online) about where the trial is running could be provided.

It is still critical for trial teams to ensure that their ‘standard’ level of participation is as burden-free as possible for participants, and that they are only collecting data that is definitely necessary.

This may not be useful if it could cause participants unnecessary concern or worry, but may be important if a trial treatment is new and its safety is not well understood.

Care must nonetheless be taken to express this in a balanced and sensitive way, to avoid unnecessary alarm or concern. Explain that the participant would be informed about any changes to their treatment and be able to ask questions.

It should be clear that if trial intervention is stopped, if will be the participant’s choice about whether aspects of participation will continue.

It is possible to suggest that they will continue to be invited to further trial follow-up visits unless they object (in line with ‘presumed ongoing consent’ approaches*).

* This means participants’ consent to a particular trial activity is presumed to be ongoing if the participant has not said they want that activity to stop, as long as certain conditions are met. For more details, see PeRSEVERE principle O5.

This includes any approaches trial staff might use to re-contact participants, or any plans for trial staff to contact other healthcare professionals (e.g. GPs, with participants’ consent) to see if they have information on how participants are doing.

It may be helpful to encourage participants to let trial staff know if they change their contact details during their time taking part in the trial (see principle D5 – encouraging dialogue).

This includes any limitations on participants’ rights to have data about them deleted if it was collected before they decided to stop participating (see principle O6 – retaining data).

Participants could be reassured that the data about them will nonetheless be kept confidential. Collected data would also only be used in line with the consent that participants previously gave and with the information already given about how their personal data would be used (based on the ‘transparency’ principle of data protection). If steps will be taken to reduce the identifiability of retained data, these could also be communicated.

It includes limitations on having any biological samples destroyed if they have already been used.

It may not be possible to stop some sorts of data collection, such as collection of serious adverse event data in some clinical trials of medicinal products where this data collection is a statutory requirement.

Content about limitations on rights could include the possibility of further contact with participants about the trial after they stop participation, regardless of their contact preferences.

This might be necessary, for example, if there is any chance of the trial team deciding that it was in participants’ best interests to share (via participants’ clinical team) new safety information about the trial intervention.

This means if a participant says they want to stop taking a trial treatment (for example) but does not say (even after having been asked) that they want to have the other participation aspects stop, then those activities can continue.

If this approach is taken, it must be clear to participants how they can express a wish for data collection to stop, if that is what they want.

Trial staff must also make reasonable efforts to find out the participant’s wishes (usually through discussion with the participant at the time they are stopping or reducing their participation [see principle D5 – encouraging dialogue]).

Regarding data collection, it should be clear that data generated prior to any participant decision about stopping data collection would still be collected for the trial (see principle O5 – continuing data collection), unless the data collection itself has confidentiality considerations (see Standard Operating Procedures).

The approach could be linked to the ‘participation tiering’ idea (see Protocol Development). For example, if a participant says they want to stop taking part but do not clarify further exactly how they want their participation to stop (even after having been asked), then a particular participation tier could apply (e.g. ‘active’ elements of participation stop but ‘passive’ ones continue). This must be made clear up front if this is the approach.

Consider if it might be helpful to convey why this sort of ‘presumed ongoing consent’ position is taken, if it might otherwise sound unfair or unreasonable.