Types of research
The PeRSEVERE principles are intended to apply to all health research with human participants that involves some active, ongoing participation from those participants.
This means the individual participants have given informed consent before taking part, and that taking part lasts for a period of time (i.e. not a one-off contribution) and involves receiving medical treatment, completing questionnaires, undergoing medical assessments or otherwise actively providing data for use in the research.
The principles are particularly relevant to clinical trials research (including randomised controlled trials), but can also apply to observational studies and other sorts of health research, if they include active, ongoing participation by individuals, as defined above.
The principles do not apply directly to research that involves only analysing biological samples that study participants have consented to be stored in a central location (for example a ‘biobank’) for research purposes, as this sort of research usually does not involve any active, ongoing participation from the individual participants (see also the related point below about storage and use of biological samples).
Similarly, the principles do not apply to research only involving data obtained from healthcare databases held by the UK National Health Service or similar public organisations. This sort of research also does not usually involve any active, ongoing participation from its participants.
It sometimes may not be done on the basis of patients’ consent*, so issues of informed consent and its withdrawal will not apply (although patients can refuse this use of data via mechanisms such as the National Data Opt-Out).
Finally, it also often involves only anonymous data, and as the researchers cannot tell who the data they have is about, there is no way for them to contact or otherwise ‘involve’ the individual research participants.
Types of participation change
Our principles mainly address study participation changes that could lead to expected data being unavailable or not measured for study analysis, for example participants no longer taking part in study follow-up arrangements (whatever those might be).
When participants only stop study treatment or intervention, but carry on with study follow-up arrangements, this should not lead to missing outcome data and is therefore mostly out of our scope.
Our principles do not apply in cases where individuals’ participation stops because the whole study is coming to a close earlier than planned.
Capacity to give informed consent
Specific arrangements apply where potential study participants do not have the mental or legal capacity to give informed consent (for example due to being unconscious, having conditions such as dementia or being under the legal age of consent [16 for most situations in the UK]) or where study participants who gave valid informed consent later lose capacity to consent during the study.
In the UK, the relevant laws include the Medicines for Human Use (Clinical Trials) Regulations for most studies involving medicines, and for other studies the 2005 Mental Capacity Act (applying in England and Wales) and the Adults with Incapacity (Scotland) Act 2000.
When dealing with these issues involving absence or loss of capacity to consent, researchers should follow the relevant local laws (including those in force outside the UK).
Although we acknowledge that understanding of the regulations in the UK may be limited, we have decided that issues around loss or absence of capacity of consent are out of scope for this version of our principles, which are focussed on study participants making decisions for themselves. However, where necessary we have noted where issues of capacity to consent may be particularly relevant.
For similar reasons, the situation where an individual gains capacity to consent during their time taking part in a study (for example if they regain consciousness, or reach the age where they may consent for themselves) is also out of our scope.
However if, after gaining capacity to consent, the individual does give informed consent to study participation, our principles will then apply.
Participants dying while the study is ongoing
If participants die while they are still participating in a study, clearly their active participation ends at that point.
However, death is inherently very different to other sorts of participation change.
Many of our principles relate to activity or events that might take place after a participation change, and so these cannot apply in the case of participants’ death.
In theory, decision-making about aspects of study involvement that may continue (such as storage and use of samples or data) might pass to others, such as relatives or carers, after a participant’s death.
However, in the UK at least, an individual’s consent given and not withdrawn (or affected by changes in capacity to consent) prior to their death is considered to persist after they die.
There is no existing obligation to inform relatives or carers about details of the participant’s participation and which aspects of it might continue or not.
There is also no clear argument that such disclosure would definitely be the right thing to do.
Considerations around consent and the possible involvement of relatives or carers in the case of participants dying while taking part in a study are likely to be complex and/or sensitive.
It might be reasonable to suggest that additional guidance or policy is needed to clarify aspects of how these complexities and sensitivities should best be managed in practice.
However, aside from a few specific places in our guidance, we have considered this issue to be out of our scope.
Improving retention
We are aware of efforts to understand how studies can be run to reduce the proportion of study participants who decide to stop participating early (for example, see reports by Brueton or Brunsdon and colleagues). This is often referred to as ‘improving retention’.
This might be by offering ethically acceptable incentives to study participants, making study participation less burdensome, or through other means.
This work is important and complementary to our principles, but also out of our scope. Instead, we are looking to achieve the aims outlined in the background to the PeRSEVERE project, no matter what individual study participants decide to do.
We suggest that researchers designing and running studies should continue to follow evidence-based best practice around improving study retention, as it continues to develop.
We also suggest that it should be routine (if it is not already) for researchers to consider, in discussion with involved patients, how to minimise the amount of time and effort taking part in the research will require of the participants. This includes limiting the amount of data collection to what is absolutely necessary.
Biological samples
We considered issues to do with storage and use of study participants’ biological samples to be largely out of our scope (this means what happens to stored biological samples if a participant decides to stop participating in a study) unless we have specifically referenced them.
However, our principles do apply to data that has been generated from analysing study participants’ biological samples.
Privacy, confidentiality and consent to use personal data
Informed consent, confidentiality and data use are usually closely linked.
Participation in research often has implications for confidentiality, for example where more people than usual will see a patient’s medical records or their name. In some jurisdictions and settings (though not often in the UK), participants’ informed consent is the basis for researchers using personal data about them.
These issues are broadly within scope for our principles, in particular where withdrawal of informed consent has implications for study participants’ confidentiality and privacy and further data use.
However, they are not our primary focus, so we have mentioned them only where they interact with the broader consent to participate in a research study.
There may also be additional considerations that we cannot realistically incorporate exhaustively into our guidance.
For example, there are specific requirements around the reliance on consent to process personal data under EU and UK law, and these requirements are quite separate to those around research consent.
We therefore suggest that readers should use our guidance alongside any national and international laws and guidelines on confidentiality, privacy and personal data use.
* An alternative route for conducting this sort of research in the UK is where access to confidential patient data for research is given via a ‘section 251’ approval. For more information see: https://digital.nhs.uk/services/data-access-request-service-dars/dars-guidance/data-sharing-standard-7b—duty-of-confidentiality