1. NRES Standard Operating Procedures (SOPs) Version 4.0 April 2009 Training Modules for Research Ethics Committee Co-ordinators Lynda McCormack, Co-ordinator East of England and Jill Marshall, NRES Learning and Development Manager November 2010

2. This training module covers: Giving an ethical opinion (SOPs Section 3)

3. Aims and Objectives By the end of the training staff will have: Understood the decisions available to the NRES REC following review of an application Looked at the delegation of authority Discussed the letters sent to the applicant Looked at regulatory authority approval Understood the difference between appeals and resubmissions Identified local issues and ways of addressing them

4. Decisions available following review: 1.Favourable opinion (standard conditions – no changes required) 2.Favourable opinion (with additional conditions) 3.Unfavourable opinion 4.Provisional opinion 5.No opinion pending referee’s advice – Op Alert 17 6.Invalid/incomplete application (rare)

5. Non-binding advice Non-binding advice or suggestions may be offered to the applicant alongside an opinion, or at any stage of the review process. Communications must always distinguish clearly between what is required (eg as part of a provisional opinion or condition of final opinion) and what is non-binding advice or suggestions that do not have to be followed.

6. At the meeting The Chair should ensure that: A clear decision is made on every application All further information or clarification required is identified Delegation of authority is agreed to review response if provisional opinion given The NRES Co-ordinator should: Record the above in the minutes

7. Letter to the Chief Investigator Letter should be sent to the CI with the NRES REC’s decision within 10 working days of the meeting. Should include: A summary of the issues (including those already resolved with the CI) List of the documents reviewed List of members present (and those that gave written comments) Declarations of interest (no detail, just statement) Names of observers Name of contact for further clarification if needed.

8. Final opinion letters Letters should be in name of Chair (but can be signed by the Vice-Chair or NRES REC office staff) – signing procedures agreed locally All final opinion letters should be sent within 60 days of receipt of application (allowing for clock stopping in meantime) Date of the opinion is the date letter sent

9. Favourable opinion with conditions NRES REC may specify only minor conditions such as: Changes to the PIS or documentation - exact wording must be specified Requirement for training Obtaining certificate of insurance

10. The NRES REC should not attach conditions: If further ethical opinion is required Significant / unspecified changes to the PIS etc are needed Operational Alert 12 refers

11. Compliance with conditions NRES REC should be notified by sponsor/CI once the conditions are met and a letter of acknowledgement should be sent by Co- ordinator within 5 days. Don’t arrange for re-review of revised documents by NRES REC or re-issue FO letter if CI requests it Op Alert 7 NRES REC’s opinion is valid even where the CI does not provide this confirmation. However, opinion is not valid if the sponsor does not ensure that conditions have been complied with. No direct functionality on RED to follow up missing confirmations but e-mail reminder can be sent to the CI, copied to the sponsor, reminding them that there is no favourable opinion if the conditions have not been met. Op Alert 22

12. SOPs Annexes B and C Standard "After Ethical Review" guidance issued with FO letters on specific projects These documents are guidance rather than approval conditions as described in 3.19- 3.27 (But there are standard approval conditions documents for RTBs and databases.)

13. SSA If the application includes a non-NHS SSA and the main NRES REC is also the SSA NRES REC then approval should be confirmed in the letter If the SSA is to be considered by another REC (the SSA REC) approval of the study can still be given. The letter generated by RED gives the option of advising that notification has not yet been received regarding the site

14. Unfavourable opinion The letter should give a full explanation of the reasons for the decision The applicant should be informed of the options available for further review - automatically generated by RED

15. Provisional opinion 2 variations on the wording when the letter is generated by RED – choose most appropriate The Committee would be content to give a favourable ethical opinion of the research, subject to receiving a complete response to the request for further information set out below. The Committee is unable to give an ethical opinion on the basis of the information and documentation received so far. Before confirming its opinion, the Committee requests that you provide the further information set out below.

16. Informal contact with applicant about REC decisions Any informal contact that co-ordinator has with researcher about any REC decision should normally be conducted via email so there is clear audit trail of what clarification is sought and what advice co- ordinator has given - Op Alert 9 Verbal advice should always be confirmed via email.

17. Delegation of responsibility NRES REC to decide at the meeting who should consider the further information once received: Chair (or Vice-Chair) Chair (or Vice-Chair) with 1 or more named member, deputy or scientific officer Sub-Committee of named members NRES REC office staff (if purely administrative or FO with conditions) Full meeting of the REC

18. Letter to applicant Letter should clearly distinguish between matters discussed and resolved, and further information requested by the NRES REC CI has max 4 months to reply from date of letter. Give details of who will be reviewing the response Anything not mentioned in the letter cannot be raised later, except in exceptional circumstances Copies of correspondence should be sent to the sponsor’s representative. If study involves NHS sites then copy to lead R&D office If appropriate also copy to Academic Supervisor

19. Response to provisional opinion Response should be from the CI. Email is acceptable. The 60 day clock will restart on receipt of complete response. If no response after 3 months then alert on RED and letter sent. (Be sensitive eg check if CI is off sick/on extended leave) If response incomplete a letter is sent pointing out missing information and 60 day clock winds back NRES REC can send further letters if further incomplete responses are received If no response after further month letter sent advising NRES REC considers application to have been withdrawn

20. Decisions following response Further information favourable opinion Further information response not complete Further information unfavourable opinion

21. Further information favourable opinion / unfavourable opinion As before for final opinion letters: Letters should be in name of Chair (but can be signed by the Vice-Chair or NRES REC office staff) All final opinion letters should be sent in 60 days The date of the opinion is the date letter sent

22. Further information response incomplete If the Committee (or delegated representative) decides that the response is incomplete or does not fully address the issues: Letter sent setting out information/clarification still required (no new issues to be raised) The 60 day clock winds back Further letters setting out information/clarification still required can be sent if necessary

23. ‘No opinion’ decision - further advice from a referee Ideally applications where referee’s advice may be needed should be identified before meeting to avoid delay Op Alert 17 NB 60 day clock does not stop during this process Op Alert 17 Letter sent to CI advising that REC seeking referee’s advice. Must not request further information/ clarification at this point because REC only has one opportunity to request further information and referee's advice needs to be considered first

24. Referee’s advice cont.... If REC decides at meeting who to consult, should be recorded in minutes If not, Chair or Co-ordinator can be appointed to identify referee Good idea to have list of suitable/willing referees per REC Centre Referee to be contacted – timescales OK and no connection with study? SOP 3.43 Send copy of application and letter with specific issues within 5 working days of the meeting

25. On receipt of referee’s advice: Referee should respond within10 working days Referee’s written advice to be considered promptly at a meeting of a sub-committee (SOP 2.49ii) NRES REC should not disclose advice given (or ID of referee without express permission) Usual rules for decisions apply

26. Regulatory Approval Responsibility of sponsor to ensure regulatory approval obtained CTIMPs Application for clinical trial authorisation (CTA) to MHRA – sponsor’s responsibility Can be in parallel or in sequence. REC required to notify MHRA of opinion – happens automatically via MHRA access to RED) If NRES REC opinion is given first, and then MRHA attaches conditions requiring further review by a REC, then a substantial amendment to be submitted

27. Regulatory Approval cont Medical devices If device is non-CE marked, modified or not used for intended purpose MHRA to give notice of no objection Again, can be in parallel or sequence. REC opinion to be copied to Regulatory Affairs Manager at MHRA Devices. Contact details on NRES website on communications with MHRA. If NRES REC opinion is given 1 st and then MHRA attaches conditions then a substantial amendment to be sent ARSAC certificates If radionuclide materials used then must be covered by the ARSAC certificate at the site. If additional radiation, new agent or novel use then further certificate to be obtained. NRES REC does not need to see certificates – they are generated as part of the SSIF

28. Insurance, Indemnity and Compensation NRES REC to consider provision for indemnity. Must be clear assurance given in application form and PIS that no fault compensation will be available under appropriate scheme Applicants to provide information to show that there is adequate arrangements. NHS organisations can’t enter into no fault compensation arrangements. GAfREC only requires NRES RECs to be reassured that appropriate insurance in place SOP 3.59 – not required to scrutinise insurance policies CTIMPs – Commercial sponsors cannot self insure – they must take out a policy with another insurer NHS as sponsor - staff with NHS contracts have indemnity – checked by NHS governance

29. Compensation for harm where liability does not arise Also known as ‘no fault compensation’ For commercially sponsored CTIMPs or medical devices ABPI or ABHI scheme – NRES REC does not need copy. Agreement is standard industry-wide form of words. For other research NRES REC to consider if no fault compensation needed

30. Compensation continued.... Independent Practitioners GPs, dentists, optometrists and staff such as practice nurses not normally covered by NHS Indemnity. They need to arrange cover Where independent practitioners conduct research on NHS patients the NHS care organisation will ensure indemnity arrangement in place (research governance) Research on private patients: REC to ensure indemnity in place Professional indemnity provides covers when research procedures are equivalent to services normally offered by the practitioner to their NHS patients. If research involves additional procedures, practitioner may need to take out additional cover and should check with medical defence organisation.

31. Further review of research given an unfavourable opinion Two options available to researcher for further review: New application, addressing issues raised Appeal NRES REC decision – same application submitted to a second NRES REC

32. New application Best if application is booked with the NRES REC that first reviewed it (first REC) as will already be familiar with issues/best placed to consider changes Application booked as usual and given new number Covering letter to accompany application explaining how issues have been addressed Changes to documentation should be highlighted If reviewed by a second NRES REC, then first NRES REC to be contacted for copies of correspondence if not provided by researcher

33. Appeal Different from resubmission: Appeal first considered by Appeal Manager (Head of Operations) who decides if can be allowed CI has to submit exactly the same application, with no changes, to a second REC CI must provide information to justify why UFO should not have been given. Should also indicate which changes proposed by first REC can be met. This will be made available to appeal REC Section 7 training module covers Appeals in detail

34. Questions in the NRES REC office about giving an ethical opinion: Experienced colleagues REC Centre Manager

35. Thanks for listening Questions and answers