Ethics Review Form for Research Databases (Lead Reviewer/REC Member)

The content and requests for further information included in this form should be discussed in the meeting as it is important the review reflects the opinion of the entire Committee as opposed to the view of an individual member/s.

Electronically saved copies of this form should be deleted after the final opinion has been issued. Comments entered into the online version of this Form in the HARP Reviewer Portal will be deleted automatically 30 days after the final opinion has been issued.

Meeting Date:

IRAS Project ID/REC Reference Number:

Study Title:

Brief overview of Research Database (optional depending on REC practice)

1. Social or Scientific Value; scientific design and conduct of the study

• Has this database (or any part of the database) previously been the subject of an application for ethical review? Is this a renewal of a Research Database which has already received a REC Favourable Opinion? (IRAS Q5) If so, the REC should check the annual progress report to identify if there are any ethical concerns relating to the management of the Research Database or to the release of data to external researchers.
• Why is the resource needed? (IRAS A7, A10 & A16)
• What type of data will be stored? What personal identifiers or particularly sensitive information will be held? (IRAS A6, A7, A11, CAG Part B Section 8 & 9)
• How will the database add value to existing sources of data in this field? (IRAS A6 & A7)
• Suitably representative public involvement in designing and managing the Research Database can provide assurances to the Committee that the people the database is intended to benefit think it is important and necessary? (IRAS A8-1, A8-2 & A9)

Ethical issues for consideration:

2. Recruitment arrangements and access to health information, and fair participant selection

• How will the data be obtained? (IRAS A6, A7, A10, A20)
• Will participation impact on clinical care? (IRAS A22 & A23)
• Will identifiable patient data be accessed outside the care team without prior consent at any stage of the project? If yes, and the database is being established in England or Wales, has an application to the Confidentiality Advisory Group (CAG) been submitted? ( IRAS Project Filter question 4, A26, A27-2, A27-3 and A27-4, A27- 5 and Part B Section 8 & 9 if applicable.
• Suitably representative public involvement in the design and management of the research database can provide assurances to the Committee that recruitment and arrangements for access to health information is fair and reasonable.

Ethical issues for consideration:

3. Favourable Risk Benefit Ratio; Anticipated benefits/risks for research participants present and future

• If informed consent will be sought, will adequate information be given upon which potential participants can make an informed decision? (IRAS A26 to A29-3)
• Is there a possibility that participants could be unduly influenced? (IRAS A31)
• Will there be an appropriate and fair assessment of the participants’ capacity to consent for themselves? (IRAS A29-1 & Section B Section 6)
• Suitably representative public involvement in the planning of the research database can provide the Committee with assurances about the points above.

Ethical issues for consideration:

4. Care and protection of research participants; respect for potential and enrolled research participants’ welfare and dignity

• Will data be effectively anonymised or pseudonymised? (IRAS A6, A7 & A11)
• Has the collection of data been justified including the release to other researchers or research organisations? Are processes in place for effective de-identification of data extracts prior to release? (IRAS A7)
• What type of engagement will there be with patients, service users and the public on the publication of research findings? (IRAS A9)
• Are there suitable systems in place to ensure the confidentiality of personal data? (IRAS A12-1, A12-2 if applicable, A13, A14, A20 & A21)
• Consider access to identifiable data within the Research Database team and security and confidentiality policies – what systems are in place to ensure the confidentiality of personal data? (IRAS A12-1 – A14)
• If applicable, are there plans to provide participants with feedback of any clinically significant information obtained in research using their data? If not, are the reasons for not providing feedback justifiable? If yes, are participants informed of this? How and who would contact them? (IRAS A22 & A23)
• Are participants provided with information about what will happen if they wish to withdraw their consent for their data to be used in research? (IRAS A32)
• Does the application demonstrate an awareness of research transparency? (for example: plans for registration, visibility of the Research Database)

Ethical issues for consideration:

5. Informed consent process and the adequacy and completeness of research participant information

• If applicable, review the provision of information to research participants about the purpose of the database, its’ procedures, potential risks, benefits, and alternatives, so that the individual understands this information and can make a voluntary decision whether to enrol and continue to participate.
• Do the terms of the informed consent as set out in the information sheets/consent forms suitably inform participants how their data will be used? (IRAS A26, A29-1, A29-2, PIS & Part B Section C if ALC and Part B Section 7 if children)
• Is consent taken as part of a process with research participants having adequate time to consider the information, and opportunity to ask questions? if applicable)
• Is the language used clear and understandable to the research participants it is aimed at? If the Database will include children, has age-appropriate information been provided?
• Has informed consent already been given to use the data for research? If no, will consent now be sought? If informed consent has already been given for use of the data in research has evidence or an explanation of the terms of this consent been provided? Consider the requirements to seek consent from new participants, further consent from previous participants, or consent from relatives where the participants are deceased. (IRAS A26 and A28-A30)
• Suitably representative public involvement in the planning of the informed consent process (where applicable) can provide assurances about the points above.

Ethical issues for consideration:

6. Suitability of the applicant and supporting staff

• Arrangements for management and oversight of the Research Database (IRAS A3)
• Expertise available within the Research Database team (IRAS A17)

Ethical issues for consideration:

7. Policy for provision of data to researchers, including arrangements for ensuring adequate scientific critique of projects and the conditions under which data will be released

• Are the applicants seeking generic ethical approval for research projects using the stored data, under conditions agreed with the REC, without requirement for external researchers to apply individually to the REC for approval? (IRAS A15)
• External researchers relying on generic ethical approval can only receive anonymous data. What are the processes for de-identifying the data before it is released? (IRAS A10, A12-1, A20, A21)
• What type of organisations will the data be supplied to? Are the arrangements for determining access to the data fair and appropriate? How will decisions on access be made? (IRAS A19, A21 & A24, A25)
• Have the conditions of data sharing agreements with external researchers been described? in particular no attempt to re-identify data subjects through linkage with other databases and no onward disclosure to third parties. What policies will apply to further storage and use of data by researchers when studies are complete? (IRAS A21 & A25)
• Will an Access Committee be established to assess the quality of applications to use the data? Who will sit on the Access Committee? How will decisions on access be made and who will be involved? Where applicable - Is the REC content to issue generic ethical approval for external researchers outside of the research database team to access the data without the need for individual project specific ethics approval?

Ethical issues for consideration:

8. Suitability of supporting information

For example: GP letter, interview schedules, questionnaires, lone working policies.

Ethical issues for consideration:

9. Other general comments E.g. missing information / application errors/ suitability of the description of the Research Database (IRAS A33)

Note: A request to change the research summary should only ever be listed as a recommendation. The summary will be published on the HRA website together with the REC’s ethical opinion.

Ethical issues for consideration:

10. If the Research Database will include Adults lacking Capacity to consent for themselves, please consider the whether the application complies with the Mental Capacity Acts: (IRAS Part B-Section 6)

1. Relevance of the research to impairing condition

The REC must consider whether the research is connected with an impairing condition affecting research participants who are unable to consent, or with the treatment of the condition. An impairing condition means a condition which is attributable to (or causes or contributes to) an impairment or disturbance in the functioning of the mind or brain.

Treatment in this context includes the provision of any clinical treatment or other health and social care in connection with the impairing condition.

2. Justification for including adults lacking capacity to meet the research objectives

The REC must consider whether or not the research could be carried out as effectively if it was confined to research participants able to give consent, i.e. is it necessary to include research participants lacking capacity in order to meet the research objectives?

3. Arrangements for appointing consultees

The REC must be satisfied that reasonable arrangements will be in place to comply with Section 32 of the Mental Capacity Act 2005 (England and Wales) and the equivalent Section 135 of the Mental Capacity Act (Northern Ireland) 2016.

This requires the researcher, as part of the recruitment strategy, to identify and consult persons (consultees) to advise on whether a person lacking capacity should take part and, in their opinion, what the person’s wishes and feelings would be likely to be if they had capacity. The research team must take reasonable steps firstly to identify a personal consultee who is engaged in caring for the participant or is interested in their welfare (but not in a professional capacity or for remuneration) and is prepared to be consulted. If no such person is available, the research team should have a strategy for appointing nominated consultees who are independent of the project in conjunction with the host organisations at each site.

4. The arrangements for recruitment in an emergency setting (if applicable)

The Mental Capacity Acts allow for recruitment without prior consultation where treatment is to be provided as a matter of urgency and it is not reasonably practicable to identify and consult with a personal or nominated consultee beforehand. Enrolment may then take place:

a) with the agreement of a doctor independent of the project; or, where this is also not reasonably practicable in the time available.

(b) in accordance with any procedure approved by the REC.

Where enrolment without prior consultation is proposed, the REC must be satisfied that this is justified in the circumstances. It should also ensure the researcher has procedures in place to seek consent from a capable research participant (if recovered) or to consult a consultee as soon as practicable after urgent treatment has been provided

5. Balance between benefit and risk, burden and intrusion

The REC must be satisfied that one of the following criteria is met by the research:

a) The research is of potential benefit to research participants lacking capacity without imposing a disproportionate burden

or:

b) The research is intended to provide knowledge of the causes or the treatment or care of the condition affecting participants lacking capacity or of a similar condition, and additionally:

• The risk to participants is likely to be negligible
• The research will not significantly interfere with their freedom of action or privacy
• The research will not be unduly invasive or restrictive

6. Additional safeguards

The REC must be satisfied, from the information in the application and any further assurances given during the review that the additional safeguards set out in Section 33 of the Mental Capacity Act 2005 (England and Wales and the equivalent Section 137 of the Mental Capacity Act (Northern Ireland) 2016 will be complied with during the conduct of the research.

These additional safeguards are as follows:

Nothing will be done in the course of the research:

(a) to which research participants lacking capacity appear to object (unless it is to protect them from harm or reduce/prevent pain or discomfort)

(b) which would be contrary to any known advance decision or statement they have made.

If research participants indicate in any way that they wish to be withdrawn from the project, they must be withdrawn without delay, except where this involves stopping treatment and there could be a significant risk to their health.

Research participants lacking capacity must also be withdrawn if any of the criteria set out in Section 32 of the Mental Capacity Act 2005 (England and Wales) and the equivalent Sections 135 and 136 of the Mental Capacity Act (Northern Ireland) 2016 no longer apply.

In conducting the research, the interests of research participants must be assumed to outweigh those of science and society.

7. Information for consultees

The REC must be satisfied that appropriate information will be provided to consultees about the research and their role as a consultee. There is no statutory requirement for the consultee to sign a form, but it is strongly recommended that the researcher uses a Consultee Declaration Form to confirm that the consultee has received the information, has had the opportunity to ask questions and has advised they have no objection to the participation of the person lacking capacity. A template for the declaration is set out in the HRA guidance on information sheets. Where carers will also be recruited as research participants in their own right, the information sheet should distinguish clearly between the two roles and the carer should sign a consent form separate from the consultee declaration sheet.

11. Issuing an Ethical Opinion – Key Principles for Requesting Further Information (RFI)

When the REC decides to issue a Provisional Opinion or a Favourable Opinion with Conditions decision, a request for further information (RFI) is sent to the applicant in order that the relevant changes can be addressed.

It is important that requests for further information are clearly articulated so that the applicant fully understands what is required and can provide a comprehensive response. It is also important that requests for further information and document changes have been agreed by the Committee as a whole (with the exception of minor spelling and typographical errors).

Please reflect on the following principles, when requesting further information from the applicant:

1. A request for further information should be focused on issues that if not resolved could cause the study to be rejected. The REC should consider carefully why it is asking for something. What are the implications of not requesting a particular point? How can the request be articulated clearly in the decision outcome?
2. Where specific changes are requested, the rationale for them should be provided. The request should describe the issue in a full sentence or paragraph. The more specific this can be the better. The REC should be absolutely clear about what it is asking and what response it requires to address the issue (if the REC isn’t clear about what is required then the applicant won’t be clear either).
3. Where a comment is being made for applicants/sponsors to take account of in the future (e.g. other applications or future updates of a document or suggestion for improvement) they should be clearly indicated. Clearly state what are mandatory requirements to address before a favourable opinion can be issued and which are suggestions or advice only.
4. Where an open request is being made, such as where further justification or clarification is requested, the rationale for this should be clearly indicated. This is particularly important where there may be an additional action based on the response received, such as a corresponding update to the Participant Information Sheet (PIS). If a corresponding change to a document will be required, then this should be mentioned in the initial request for further information.
5. It should always be clear for the sponsor that an updated version of the relevant documents should be provided when responding to the RFI.