Using IRAS to apply for ethical review; procedures for SSA

1. Using IRAS to apply for ethical review; procedures for SSA David Neal Head of Policy and Deputy Director, NRES

3. Philosophy Clarify roles and responsibilities Avoid duplication; also avoid issues falling between the cracks Ensure consistent guidance from relevant bodies Simplify procedures, reduce bureaucracy consistent with need to comply with regulation and protect subject safety

4. Applications to ethics committees Schedule 3 to the Clinical Trials Regulations lists information to be included in the application document European Commission guideline on applications to ethics committee (ENTR/CT2)

5. Regulation 15 - matters the ethics committee must consider Relevance of trial and its design Risk/benefit analysis Protocol Investigator brochure or SPC Investigator(s) and supporting staff Quality of the facilities Consent process / PIS Recruitment arrangements Justification for including minors or adults lacking capacity Insurance, indemnity and compensation Rewards / payments Any sponsor/site agreements relevant to rewards

6. Site-specific assessment The Regulations imply a requirement for the �main ethics committee� to approve each site and investigator in a trial SSA is a check that the site, investigator, supporting staff and facilities are suitable to conduct a particular trial

7. NRES SOPs Revised SOPs to be issued on 25 March 2009 (version 4.0) Section 4 of the SOPs set out procedures for SSA Issued on a consultation-in-use basis, leading to further revision later in 2009 in light of feedback from RECs and other stakeholders NRES SOPs will be formally adopted by AAPEC and apply to Phase 1 RECs outside the NHS

8. Responsibility for SSA � NHS sites From 1 April 2009, responsibility is transferred to NHS R&D offices SSA integrated within standard NHS research governance review Ethics committee gives a favourable opinion subject to permission from the NHS organisation

9. Responsibility for SSA � non-NHS sites Responsibility continues to lie with the ethics committee SSA is undertaken either by �main REC� (as part of main review) or by the local REC for the site, as appropriate If undertaken by another REC, this REC (�the SSA REC�) notifies the outcome to the main REC, which then formally approves the site

10. Phase 1 SSA Network (April 2008) NRES/AAPEC has appointed designated SSA RECs to undertake SSAs at each commercial Phase 1 trial site Where the SSA REC is also the main committee for the ethical review, SSA will be an integral part of the main review Where it is a different committee, the SSA REC provides advice on the site to the main committee within 14 days and in parallel with the main review

11. Applying for SSA � where the SSA REC is also the main REC Sponsor / Chief Investigator includes SSI Form and supporting documentation with the main application package

12. Applying for SSA � where the SSA REC is not the main REC CRO / Local Principal Investigator submits SSI Form and supporting documentation to the SSA REC as soon as the main application has been validated for review SSA application may be made in parallel with main review or at any time subsequently (e.g. to add new site)

13. Current content of SSI Form Site/CRO name MHRA accreditation? Management/monitoring arrangements Investigator (plus CV) and supporting staff Identifying subjects Consent procedure (plus local PIS) Advice for subjects Complaints Notifying GPs Any special facilities or emergency measures Any local variations to protocol procedures Insurance / indemnity Over-volunteering

14. Supporting documentation for SSA CV for Principal Investigator Local version of Participant Information Sheet (including contact details and other site-specific information) Accreditation certificate (where applicable) Copy of protocol and main application form for information only where SSA REC is not the main REC for the trial Other documentation may be requested by SSA REC

15. Review of SSI Form and documentation requirements Remove question about CRO insurance Consider removing any unnecessary questions, e.g. if unit is accredited by MHRA can we disable questions on issues addressed in accreditation?  Consider any other suggestions from RECs and CROs Populate background information about purpose and design of trial from Part A of IRAS � for information not for review, avoids need to provide copy of main application form and protocol to SSA REC

16. Undertaking SSA Documentary check Minimum of two members, can be in correspondence Local investigator may be asked to provide any further information within 14 day timeline

17. Outcome of SSA Where SSA undertaken by main REC, site will be approved as part of its favourable opinion (FO) letter Where SSA undertaken by a different REC: SSA REC notifies the main REC of its advice electronically via the Research Ethics Database (RED) or via email if not using RED If no objection, main REC confirms approval for site in FO letter If objections, SSA REC should give reasons and the issues should be discussed between the RECs; final decision is the responsibility of the main REC

18. Site visits by SSA committees Not routinely required for SSA Occasional visits (e.g. annual) may be helpful for familiarisation Site visit recommended for a new site not yet inspected by the MHRA Any concerns identified in visits can be reported to the GCP Inspectors

19. General advertising and screening Advice on non-trial specific advertising and screening procedures is outside the scope of ethical review under the Regulations NRES encourages SSA RECs to provide advice on a voluntary basis

21. Objectives Background to IRAS Using IRAS Recent developments Forthcoming priorities Potential

22. Aims Web-based system Capture all the information required to apply for relevant permissions and approvals for health research in the UK Researchers enter information about their project once Use filters to ensure data collected appropriate to the type of study, approvals and permissions required Build on familiar features of NRES on-line form

23. Builds on� Creation of standard R&D application form alongside COREC online form (2005) Inclusion of study-wide R&D issues into REC form to minimise duplication, and modification of some questions to allow dual use of REC form (2006) Creation of Site-Specific Information Form (SSI Form) for both Site-Specific Assessment and R&D review (2007)

24. Who was involved?

25. Which applications are included? Administration of Radioactive Substances Advisory Committee (ARSAC) Gene Therapy Advisory Committee (GTAC) Medicines and Healthcare products Regulatory Agency (MHRA) � Medicines and Devices Ministry of Justice � England and Wales NHS / HSC research offices NRES / NHS / HSC Research Ethics Committees National Information Governance Board (NIGB, formerly PIAG) � England and Wales

26. Development & Consultation Launched January 2008 Consultation-in-use to July 2008 Version upgrades � import/ export EudraCT and IRAS; entry point for NIHR CSP; electronic authorisations and improvements in response to feedback Existing (parallel) application systems will be withdrawn in due course Feedback continues to be encouraged from users on the content, design and practical operation of IRAS to iras@nres.npsa.nhs.uk

27. IRAS usage Use of IRAS will be the preferred application route from April 09 Take-up is encouraging with half of REC applications now made using IRAS The NRES application form system will be closed for new applications at the end of March 09 Transitional arrangements will be made for existing applications in progress, applications are not transferable

28. Using IRAS Setting up a user account Create a project Enter information about a project Navigating the system and key functionality

29. How to set up an account First enter web address to your browser: www.myresearchproject.org.uk If you already have existing NRES (COREC) account you can use your current log-in and password. If you do not have an existing NRES account you can easily create a new account by following instructions on help page

30. Log in page Same log in as for NRES form system can be used Can create a log in and dummy applications to �play around� with the systemLog in page Same log in as for NRES form system can be used Can create a log in and dummy applications to �play around� with the system

31. Creating a new project

32. IRAS � project filter Short list of questions about the project Dynamic � subsequent filter questions may alter depending on responses Generates project dataset questions and application forms required for study type Answer all the questions carefully and refer to question specific guidance as necessary

33. This open the Project Filter which determines what questions will apply for the type of study, and what applications are requiredThis open the Project Filter which determines what questions will apply for the type of study, and what applications are required

34. How does IRAS work? It consists of a single integrated dataset This is the set of questions and answers for all the questions in all the application forms The set of questions that need to be answered by a researcher will depend on the type of study and the types of applications required The application forms for each reviewing body are generated from the single dataset The single dataset and application forms cross-populate i.e. information about the project in response to a question is entered only once Information about the project can be completed in application forms or dataset Information about the project can be completed in application forms or dataset

38. IRAS Functionality Filter, integrated project dataset and application forms on the left Select each form to show tabs relevant to that form on the right hand side of page: Navigation tab � questions to complete Other tabs � functions available for that form Move around system using: Underlined links (e.g. dataset, forms or question / sections) Tabs Buttons (e.g. print, save, navigation) Following slides illustrate layout and functionalityFollowing slides illustrate layout and functionality

39. Printing and submitting application forms Each review body has different submission requirements Select the appropriate form on the navigation page and then select the submission tab for specific guidance To print hard copy for submitting follow instructions on submission tab and create submission code NOTE: Remember application forms are submitted NOT the integrated project dataset!NOTE: Remember application forms are submitted NOT the integrated project dataset!

40. �Locking� forms and submission codes Application forms in IRAS cannot be locked Instead of a �lock code� IRAS allocates a �submission code� once the applicant proceeds to final submission This code will appear on the foot of the application form on print-out An audit trail is created of the dataset at the time at which a submission code is generated. It is the responsibility of applicants to keep their IRAS project dataset up to date When applicants make changes to the dataset following a submission, they will be prompted to consider whether other review bodies need to be notified of the change NRES forms were �locked� � this does not take place in IRAS because IRAS collates information for multiple review bodies. That is information may continue to be added once one form is submitted to allow for other applications to madeNRES forms were �locked� � this does not take place in IRAS because IRAS collates information for multiple review bodies. That is information may continue to be added once one form is submitted to allow for other applications to made

41. IRAS features Contacts � keep details of collaborators Standard CV Electronic authorisation

42. Contacts Enables you share contact details across all your projects Access from menu bar Or whenever you see the icon Build up an address book: Yourself You collaborators

43. Within the dataset, this icon allows you to enter contact data that you have already savedWithin the dataset, this icon allows you to enter contact data that you have already saved

44. These are all available in My Contacts and you simply select and click to copy into the datasetThese are all available in My Contacts and you simply select and click to copy into the dataset

45. Electronic authorisations New functionality from December 2008 to allow electronic authorisation in IRAS as alternative to ink signature Authorisation operates by secure email transfer, with audit trail confirming what has been authorised, when and by whom Can be used for e.g. R&D/SSI Forms, sponsor declaration, academic supervisor, radiation experts Some ink signatures still required, in particular CI declaration on REC application for CTIMPs

46. Help and support Throughout system green �i� button leads to Question Specific Guidance Contacts Review bodies Technical support Help section: QSG for each section Standard blank forms to print off

47. Technical queries on IRAS to: helpdesk@infonetica.net Feedback on IRAS to:iras@nres.npsa.nhs.uk

48. IRAS Developments Complete CSP link (November 08) Changes in response to initial consultation (December 08) Electronic authorisations (December 08) Full EudraCT dataset (March 09) In progress Social Care REC (April 09) Skeleton dataset for �old NRES form study� in IRAS (May 09) Agreed Review dataset EudraCT Notice of Amendment Medical Research Information Service (NHS Information Centre) National Offender Management Service (prisons/probation)

49. IRAS potential Considerable potential for further development: Facilitate trial registration Direct electronic submission and decision notification Safety and end of trial reporting