1. NRES Standard Operating Procedures (SOPs) Version 4.1 April 2009 Training Modules for NRES REC Co-ordinators Jill Marshall NRES Learning and Development Manager August 2010

2. This training module covers: What is required before the meeting to process new applications (SOPs Section 1) Expedited Review (SOPs Section 8)

3. Aims and Objectives By the end of the training staff will have: Discussed SOPs re procedures to be undertaken before the NRES REC meeting Understood importance of correct application of SOPs when processing new applications for meeting, and when expedited review may be necessary Identified any issues around local application of SOPs and agreed action to address any issues identified

4. Two types of research application: 1.Research involving Clinical Trial of Investigational Medicinal Product (CTIMP) 2.All other research (ie any research not involving the use of a CTIMP)

5. Types of NRES RECs and what they can review Recognised NRES RECs: Type 1: Phase 1 clinical trials in healthy volunteers taking place anywhere in the UK (Type 2: no longer exist) Type 3: Clinical trials in patients taking place anywhere in UK Authorised NRES RECs: Any research within NRES REC remit other than CTIMPs

6. Booking research applications - Central Allocation System (CAS) Clinical trials of medicinal products (CTIMPs) Studies for review by ‘flagged’ NRES RECs All bookings made by applicant by phone CAS booking number for Researchers only: 0845 270 4400 CAS number for NRES REC Co-ordinator queries only: 0161 65 77823

7. Special allocations – booked via CAS for allocation to ‘flagged’ NRES REC Prison Medical devices Adults lacking capacity to consent for themselves Research Tissue Bank (RTB) Research Database (RD) Studies with US Government funding

8. Exceptions Phase 1 trial in healthy volunteers – researchers book direct with Type 1 REC List of Phase 1 committees on website, includes some committees established outside NHS

9. Local allocation system (LAS) All other research LAS bookings – local booking checklist Varied queries at time of booking Take account of researcher’s preferences re committees/dates Timescales – application and supporting documentation submitted to NRES REC within 4 working days of booking

10. Tips when booking in via LAS … Ask questions in right order Can take 5-15 minutes – allow time Don’t complete the form/integrated dataset for the CI – R & D can help in that way

11. Documents to expect in an application Application form (ink signature needed for CTIMPs only) Application checklist Chief Investigator’s CV Protocol x 6 copies Investigator Brochure x 3 copies (CTIMPs only) Information sheet(s) Consent form(s) Various other documents depending on study

12. When you receive an application Date stamp documents to indicate delivery date Validate within 5 working days (QA report) Purpose of validation Audit trail (QA report) Follow validation criteria (national and local lists) Check filter on IRAS form and RED Enter all documents on RED Validation date (day 1) = working day on which the complete application, including all relevant signatures and all supporting documents, is delivered to the address of the REC, either in electronic or paper format (SOP 1.43)

13. Things to watch out for…. Consent form must include standard paragraph giving permission for access to records by sponsor and if applicable regulatory authorities (Op Alert 3) Non-NHS sponsored research must have evidence of insurance/indemnity (Op Alert 7) Correct filter ticked on IRAS form – especially CTIMP, Human Tissue, Radiation (Op Alert 12) If any doubt re study type, refer to SOPs Annex F - MHRA algorithm to decide whether an application is a CTIMP and also Clinical Trials Helpline. All questions answered (Op Alert 12)

14. More things to watch out for… Single site studies booked only with RECs within own domain (Op Alert 12). Can go to another domain only with NRES Managers’ permission Co-ordinators of RTB / RDB flagged RECs: check all new applications to see if investigator proposes to involve adults lacking capacity. If REC is not also flagged for MCA applications need to seek advice from an ALC flagged REC as part of review process. NB where NIGB approval is in place, MCA does not apply. (Op Alert 13) Now that e-authorisation functionality available on IRAS, must insist on IRAS declaration by sponsor’s representative being signed (wet ink for CTIMPs only) or electronically authorised on original form. Sponsor can provide additional letter of support if wishes but should be in addition to IRAS declaration (Op Alert 19)

15. Even more things to watch out for: Co-sponsorship – IRAS Q A64 (Op Alert 15 /16) Ionising radiation – IRAS filter and Part B section 3 (Op Alert 15) For CTIMPs the sponsor or sponsor’s legal representative must be based in European Economic Area; for a non-CTIMP a legal representative based in the UK must be appointed if sponsor is outside UK (Op Alert 16) For CTIMPs check that CI is an 'authorised health professional‘ as defined in the Clinical Trials Regulations and SOPs (Op Alert 22 – reflected in updated Validation Checklist)

16. If application is valid … Check contact details have uploaded to RED Allocate to agreed meeting agenda Generate standard acknowledgement letter via RED and upload edited version to RED ‘history’ for application Send to applicant within 5 working days’ of receipt (can be emailed in Word format) Copy papers ready for meeting

17. If application is not valid … Identify all outstanding issues Assess whether enough time before the meeting to address issues If minor, contact researcher/CRO and ask for complete set of papers (should mark on RED as invalid while sorting out) If major, mark as invalid on RED and issue standard letter to applicant.

18. Invalid studies – RED functionality Problem with marking as invalid whilst chasing for missing documents/information: disappears from work area RED functionality now provided: ‘validation under consideration’ button Will provide useful information on number of applications received incomplete

19. Less common situations …. Mandatory transfer of applications (1.59-1.64) SOPs Annex K covers transfers from GTAC (1.73- 1.75) Revision of applications following submission (1.77- 1.82) Withdrawal of applications (1.83) Applications not within scope of NHS REC (1.84 - 1.87) – Co-ordinators to seek guidance from Centre Manager before advising applicant that application not within scope of NHS REC

20. When mandatory transfer of applications is necessary (1.59-1.64) If receiving NRES REC not allowed to review (eg CTIMP submitted to authorised NRES REC). Clock continues ticking from date of receipt by first NRES REC) NRES REC is named in application as CI or another key investigator/collaborator in the research Transfer not necessary where member/ deputy member is academic supervisor for student applicant but interest should be declared under procedures in paragraphs 2.57-2.61

21. Revision of applications following submission (1.77-1.82) Generally no revisions allowed to application that is validated and booked, prior to NRES REC meeting If significant changes required – withdraw application and record on RED including reason Changes between review and response can be incorporated in response. At discretion of chair whether reviewed with response If additional changes too major, Chair can: reject or ask for application to be withdrawn and re-submitted Exceptionally, a Notice of Substantial Amendment to a CTIMP can be submitted either with the initial application or during ethical review if significant changes have been requested by the MHRA or another EU Competent Authority (SOP 3.83 and 5.11)

22. Withdrawal of applications (1.83) Once application is withdrawn (by applicant or NRES REC) record as such on RED including reason for withdrawal SL26 to be sent to applicant Re-submission must be booked as new application with new reference number

23. Applications not within scope of NHS REC (1.84 -1.87) If does not require ethical review under CT Regulations or other legislation, and is outside remit of REC as per GAfREC, REC not obliged to review However strongly encouraged to review and give ethical opinion on voluntary basis Chair’s decision

24. Applications submitted retrospectively (1.88-1.90) If applicant discloses that research has already started without FO, is breach of research governance within NHS If a CTIMP, criminal offence may also have been committed in contravention of CT Regs Application to be recorded as invalid Report to Centre Manager, who will seek advice from Head of Operations re reporting to outside agencies / whether appropriate for NRES REC to give a voluntary opinion

25. Expedited review (Section 8) Exceptionally, may need to start a research project urgently for reasons of public policy, for example: A research field causing public anxiety An urgent threat to public health A unique opportunity for research that is likely to be temporary (eg vCJD, pandemic flu)

26. Process (suggest refer to SOPs each time) CI approaches NRES Director (not via REC bookings) NRES Director arranges validation of application NRES Head Office allocates to existing NRES REC or sometimes establish a special NRES REC just for this application Process as per normal application, except that NRES Head Office will specify time periods required for processing application 26

27. References/more information: REC SOPs Section 1 and Section 8 http://www.nres.npsa.nhs.uk/news-and publications/publications/standard- operating-procedures/ Operational Alerts – available on Extranet http://www.nres.npsa.nhs.uk/rec-community/nres-staff-extranet/ http://www.nres.npsa.nhs.uk/rec-community/nres-staff-extranet/ QA Report http://www.nres.npsa.nhs.uk/news-and-publications/publications/quality- assurance-reports/ Operational Bulletins Compendium http://www.nres.npsa.nhs.uk/news-and-publications/publications/nres- bulletins/

28. Questions in the REC office about processing new applications Colleagues SOPs Mentor RED Mentor REC Centre Manager

29. Thanks for listening Questions and answers