2. Risk to participants

NHS/HSC organisations should ensure that potential participants receive accurate information on any research that they may be approached to take part in. NHS/HSC organisations have a duty for ensuring that any legislation relating to that research is followed, thereby mitigating any risk to those participants.

2.1 Participant information / consent documents and consent process

Introduction

Potential participants in most studies need information upon which to base their decision to take part or not (except, for example in the case of recruitment in emergency situations).

Consent should be given by a clear affirmative act such as by a written statement, including by electronic means or by an oral statement. This could include ticking a box when visiting an internet website or another statement or conduct which clearly indicates in this context the data subject’s acceptance of the proposed activity, such as the return of a questionnaire. Silence, pre-ticked boxes or inactivity should not therefore constitute consent.

Study wide reviewers should ensure that the process of identifying potential study participants and taking consent complies with the common law duty of confidentiality. It should be noted that possession of a research passport, Honorary Research Contract or Letter of Access does not in itself provide a legal basis for researchers to access data for the purposes of identifying potential study participants. See section 5.1 for further details.

Participant information sheets and consent forms are only part of the information given to potential participants during the informed consent process. The process of seeking informed consent may also involve a discussion between members of the research team and the potential participant. Schedule 1 (GCP) of The Medicines for Human Use (Clinical Trials) Regulations 2004 require that the potential participant (i.e. the subject, under Part 3(1)), or the person with parental responsibility or the legal representative (Part 4(1) and Part 5(1)), has an interview ‘in which they are given the opportunity to understand the objectives, risks and inconveniences of the trial and the conditions under which it is to be conducted’. The potential participant may also have discussions with an independent person e.g. family member, or GP. It is not expected that the consent form has a clause for every activity, on the proviso that participant activity is clear in the PIS.

Where multiple information sheets have been provided for different participant groups, for example those participating in different arms of the study, then these should each be reviewed. Each PIS should include only information relevant to the group at which it is aimed. In studies under review by an NHS/HSC REC comment should be made by study wide reviewers on the sponsors decision to provide, or not to provide, different PIS documents for different study groups, as this is a judgement for the REC.

Where it is possible that criminal or other disclosures requiring action could occur during the study the sponsor should describe its process for managing this, including where disclosure to other care professionals (such as social services) or the police may be required. The fact that such disclosures may be required should be detailed in the PIS.

Where Participant Identification Centres are to be used, or where a participant will be under the care of more than one organisation during and for the purpose of the research project, the information provided to potential participants should clearly set out the responsibilities of the various organisations to the participant for specified elements of the study.

Research ethics committees consider the ethical implications of the information provided to potential participants, and of the consent process and the risk/benefit ratio of the trial, as it applies to participants, where relevant. NHS organisations need to be assured that potential participants receive accurate information on the research and that any legislation relating to that research is followed.

Potential ‘health-related findings’ (HRFs)

During any study involving human participants, researchers may make a finding that has potential health or reproductive importance to an individual participant. Potential ‘health-related findings’ (HRFs) include incidental or unsolicited findings – a finding ‘which is discovered in the course of conducting research, but is beyond the aims of the study’, and pertinent findings that relate to the aims of the study. HRFs may result from many types of research involving human participants, such as imaging and genetic studies and studies involving physiological measurements or assays. Depending on the research context and the type of tests involved, HRFs will vary in both their nature and the frequency with which they arise. HRFs may arise in clinical trials, stand-alone studies, or in longitudinal studies that involve a range of tests conducted by different researchers over an extended period of time.

MRC and the Wellcome Trust have provided guidance on this topic and consider that it is appropriate for researchers to feed back HRFs where the potential benefits of feedback to an individual clearly outweigh the potential harms and it is feasible to do so. However how best to handle these findings remains a topic of debate and will likely be guided, in any specific study, by the relevant research context. Since the position is legally untested, it is unclear whether, and if so to what extent, researchers owe a specific duty of care to participants under UK laws with respect to HRFs.

It is important to note that the lack of a clear legal position does not affect the ethical considerations. The sponsor should explain how they plan to handle any HRFs and justify the position to, or to not, inform participants of these. It is recommended that the sponsor seek advice from those with lived experience of the condition under study to develop their position.

Study wide reviewers should ensure that the sponsors proposals in relation to HRFs are clearly expressed, and in England and Wales detailed in the Initial Information for REC form, to enable the REC to make a decision regarding the appropriateness of these proposals.

Research involving children

Consent can be given on behalf of the minor by a parent, or person with parental rights and responsibilities (Scotland) and assent obtained from the child. Information must be provided in an age appropriate manner so that the child is fully informed and involved in the consent/assent process in a manner that is appropriate to their age, understanding and the complexity of the study. There is not a legal basis for assent, however it is accepted as a documented record that the child or young person is not dissenting to participate. Young people over 16 are presumed to be capable of giving consent on their own behalf to participate in Clinical Trials of Investigational Medicinal Products (CTIMPs).

In research other than CTIMPs there is no statute in England, Wales or Northern Ireland governing a child's right to consent to research activity. Case law suggests that if a young person has sufficient understanding and intelligence to understand fully what is proposed and can use and weigh this information in reaching a decision (i.e. they are 'Gillick competent'), he or she can give consent to treatment. In the absence of law relating specifically to research, it is commonly assumed that the principle of 'Gillick competence' can be applied not only to consent for treatment, but also to consent for research. A child / young person's right to give consent is dependent upon their capacity to understand the specific circumstances and details of the research being proposed, which in turn will relate to the complexity of the research itself.

In Scotland The Age of Legal Capacity (Scotland) Act 1991 states that a ‘A person under the age of 16 years shall have legal capacity to consent on his own behalf to any surgical, medical or dental procedure or treatment where, in the opinion of a qualified medical practitioner attending him, he is capable of understanding the nature and possible consequences of the procedure or treatment.’ Under the Children (Scotland) Act 1995 children are presumed to have capacity to form a view from age of 12. However, capacity is a fluid concept and will depend on the complexity of the information and the research study and the understanding of the child, this must be assessed and documented by the person taking consent/assent. Although children with capacity have the right to give their consent, they also have the right to defer this responsibility to the person(s) with parental rights, to choose to assent and most importantly to dissent to their participation. Furthermore, for practical reasons it is not advised to consent a minor to participate in research without parental agreement, this should be documented in a parental consent/agreement form.

Where an individual is recruited to a study and, during the course of their involvement, will reach the age of majority the researchers should make arrangements to seek consent from that individual (where applicable), unless they have previously provided consent in their own right to participate. This does not need to be undertaken immediately, but should be sought as soon a reasonably practical, for example at the individuals next study visit.

It should also be noted that Data Protection legislation allows for consent to be relied upon as legal basis for children from 13 years of age. This does not mean that consent SHOULD be relied upon and it is unlikely that it would be relied upon in research (see section 5.1).

Electronic consent

HRA and MHRA have published a joint statement on seeking and documenting consent using electronic methods. This is supported and endorsed by the UK health departments in Northern Ireland, Scotland and Wales and confirms that electronic methods may be used for seeking, confirming and documenting informed consent for participation in research and sets out joint expectations regarding the use of electronic signatures in CTIMPs. Electronic methods may therefore be used for seeking, confirming and documenting informed consent in research studies including CTIMPs. Information about the trial does not have to be in writing and can be provided to potential participants using electronic methods. Informed consent must be recorded ‘in writing’. However electronic methods for documenting consent can be considered to be in writing.

The UK eIDAS Regulations (SI 2016/696), defines an electronic signature as ‘data in electronic form which is attached to or logically associated with other electronic data and which is used by the signatory to sign’. The Medicines for Human Use (Clinical Trials) Regulations 2004 specifically allows for the use of electronic signatures as a method of signing documents referred to in the Regulations.

Study-wide considerations

Consider the proposed consent process to ensure that any legal implications presented by the study are addressed. Any specific requirements within the participant information sheet and consent process that may have local implications should be highlighted.

The participant information sheet should clearly describe the study, including the arrangements for potential participants’ involvement, and be consistent with the other study documents (protocol, IRAS form/project study information form etc.).

Where it is possible that criminal or other disclosures requiring action could occur during the study has the sponsor described its process for dealing with these and detailed the need for disclosure in such cases in the PIS.

In Clinical Trials the PIS should include a short description of the drug, device or procedure being tested and describe the stage of its development. The potential side effects of these interventions should be clearly set out in the participant information sheet. Some pragmatic trials may compare two or more medications which are standard of care for patients with the condition being investigated, and participants (or centres) are randomised to receive one of the standard care medications. Where this is the case, it is acceptable for the participant information sheet to simply state that the side effects are described in the information leaflet which comes with the medicine (or similar).

The participant information sheet should detail the procedures that participants will undertake during the trial, including all research exposures to ionizing radiation and if the study will involve the analysis of DNA/RNA. If different groups participants will undergo different procedures during the trial then this should be clear and, if these are significant, different PIS documents provided for each group.

Where relevant, consider the accuracy of the information describing which organisation holds the duty of care to participants for the purposes of the study (for example when participants are recruited at PICs but the duty of care remains with the research site) at which times during the study, particularly if this will change during the course of the study.

A description of the study insurance/indemnity and compensation should be provided in the PIS which is proportionate to the study type. This should always be provided in the case of clinical trials and other interventional studies. If a description of ABPI compliant compensation arrangements is given in the PIS it should not be limited to provision of costs for medical treatment. (See section 4.3 for detailed requirements).

Consider the accuracy of any specific requirements relating to study treatment and a participant’s care after their participation in the study. The arrangements for care after research should not lead to expectations by participants of care that cannot be guaranteed. Where specific arrangements for post-study care are described, the sponsor must specifically describe the arrangements for provision including how such provision will be funded (see section 4.3 for detailed requirements).

The full study title and IRAS reference should be present on both the participant information sheet/s and informed consent form/s, except in circumstances where inclusion of the full study title would not be appropriate. This is in order that participants have a single reference for a study.

Has the sponsor detailed their arrangements for the collection, analysis, storage and disposal of Human Tissue in the PIS (see section 5.4 for detailed requirements).

Has the sponsor detailed in the PIS their arrangements for the collection, use, sharing, security and integrity of patient data, including what will happen to it following the end of the study and have they included relevant information further to legislative requirements, such as in respect to GDPR transparency information? (see section 5.1 for detailed requirements).

Where children are to be included as participants, arrangements for taking consent and, where appropriate, assent should be clear in the protocol and the different information, consent and (where applicable) assent documentation should be clearly labelled for use. It should be clear (where applicable) what arrangements will be in place for obtaining consent from participants assented as children upon attaining majority, should they do so whilst still participating in the research.

Where Participant Identification Centres are to be used there should be a clear process for providing information to potential participants. It should be clear who is responsible for which aspects of the process.

Has the sponsor explained their proposals for the management of Health-related findings and have they justified their decision to, or not to, provide these to participants. Where the sponsor does propose to provide these to participants is there a clear pathway by which they will do so.

Where the sponsor proposes to utilize electronic consent, it should be clear for all study types:

• how it will be possible to verify which version of the information sheet and consent form the electronic signature applies to?
• what methods are in place to ensure that the person signing the electronic consent form is the person who will be participating in the research study?

For CTIMPs:

• how it will be ensured, for CTIMPs that the source consent documentation is available for inspection during and after the end of the trial according to the legally required retention period
• how the site will retain control of the informed consent process and documentation so that personal identifiable data are not inappropriately disclosed beyond the site to either sponsors or third-party vendors?
• where a sponsor has commissioned a third party to provide an eConsent system, are the necessary information governance arrangements in place to ensure that participant confidentiality is protected with appropriate access and retention controls to the system? Where the sponsor is responsible for auditing, ensuring compliance, and maintaining access controls to the eConsent system they may provide the appropriate certifications to the site as needed
• how will a copy of the informed consent documentation (information sheet and signed consent form) be provided to the participant and retained in the investigator site file?
• how the sponsor will enable MHRA Inspectors access the eConsent system in a readily available way during triggered, short notice or unannounced inspections?
• where advanced or qualified electronic signatures have been used, whether an inextricable link be maintained between the metadata (the information in the electronic record that gives context, meaning, and security attributes to the data) and the document, thus demonstrating the electronic signature’s authenticity for as long as applicable legislation requires, dependent on the type of trial?