Document Title: Trust Approval and Research Governance

Document Title: Trust Approval and Research Governance Document Number: SOP034 Staff involved in development: Job titles only Document author/owner: Directorate: Department: For use by: RM&G Manager, R&D Administration Manager, Research Officers R&D Administration Manager Research and Development Research and Development NHS Staff Trust-Wide Review due: October 2017 THIS IS A CONTROLLED DOCUMENT Whilst this document may be printed, the electronic version maintained on the Trust s Intranet is the controlled copy. Any printed copies of this document are not controlled. Papworth Hospital NHS Foundation Trust. Not to be reproduced without written permission. Key Points of this Document This document sets out the procedures to be followed by all Staff members who are involved in the initiation, set-up and running of research. It aims to provide clear guidance on how research studies should gain Trust approval and maintain their approved status to ensure full compliance with the Research Governance Framework for Health and Social Care (2005). Version 5.0 Review Date: October 2017 Page 1 of 18

1 Purpose and Content a. This document defines the Trust s research SOP for the Research Governance Project Approval System (RGPAS) that covers all research studies and service evaluations running at Papworth. The document defines the procedures used to obtain permission for research studies including the preparation and submission of the relevant documentation to ensure that the correct approvals are in place. b. The document clarifies the requirements for obtaining permissions as described in Good Clinical Practice (GCP: a standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected ). c. The document aims to provide clear guidance on the Trust s processes for verifying that all aspects of the study comply with national legislation and guidance, such that the regulatory green light can be authorised, and NHS permission granted. This document also covers the process for continued NHS permission following amendments to the conduct of a study. d. The Trust is required to meet various national performance targets for research studies. This document defines the starting date for measurement of performance. 2 Roles & Responsibilities a. This Policy applies to all personnel that are conducting research at the Trust including: staff that are full or part-time employees of the Trust, those working at the Trust with employment contracts funded partially or wholly by third parties including those within CUHP AHSC and those seconded to and providing consultancy to the Trust, and to students undertaking training at the Trust. b. Staffs working on a research study are all responsible for ensuring that the study has the relevant approvals in place for it to be performed at Papworth Hospital. c. The Principal Investigator, or delegated personnel, is responsible for the submission of all the required information to the Research Governance Team, during the Trust Approval process. d. The Principal Investigator, or delegated personnel, is responsible for the submission of all required information to the Research Governance Team, following an amendment to the study. Version 5.0 Review Date: October 2017 Page 2 of 18

3 Policy a. This SOP is mandatory and, as per the Trust s Information Governance and Records Management framework, non-compliance with may result in disciplinary procedures. 4 Procedure 4.1 Process Map 1: Sponsorship Review. See 4.4 Sponsorship requested Documents required See 4.4.2 RGPAS committee sponsorship review conducted Recommend sponsorship in principle? Yes No Yes with conditions Feedback and advice given to CI Conditions actioned R&D form completed and signed REC application completed and signed R&D form submitted in IRAS REC application submitted in IRAS NHS permission process initiated See Process Map 2 Version 5.0 Review Date: October 2017 Page 3 of 18

4.2 Process Map 2: Local Review. See 4.5 NHS Permission requested - Non Sponsored studies Documents required: See 4.5.2 RGPAS committee local review conducted From Process map 1 Valid Research Application (VRA) submitted See 4.6.3 NHS Permission requested - Sponsored studies Recommend Trust Approval in principle? Yes Governance Checks conducted No Yes with conditions Feedback and advice given to PI Conditions actioned Additional documents required See 4.6.3 No Regulatory Green Light Achieved? See 4.7 Yes Trust approval letter generated NHS Permission granted Version 5.0 Review Date: October 2017 Page 4 of 18

4.3 Definitions 4.3.1 RGPAS a. The Research Governance Project Approval System (RGPAS) is the process for verifying and issuing the regulatory green light and NHS permission for all studies to commence within the Trust. See 4.13 4.3.2 RGPAS committee review: a. The RGPAS committee meet fortnightly to review applications for sponsorship and proposals to host research studies. The committee may recommend sponsorship or approval in principle, pending satisfactory completion of governance checks. See 4.13.2 4.3.3 Regulatory Green Light (RGL): a. The regulatory green light verifies that all aspects of the study comply with the Clinical Trial Regulations and other national guidelines and standards prior to granting NHS permission. See 4.7 4.3.4 Valid Research Application (VRA): a. A Valid Research application (VRA) is the minimum document set required to start local governance checks, as defined by the NIHR. Date of Submission of the VRA for a research study is defined by the NIHR as start date for calculation of performance data metrics. See 4.6.2 and 4.6.3. For further guidance on VRA see http://www.nihr.ac.uk/policy-andstandards/performance-in-initiating-and-delivering-research.htm. 4.3.5 Proportionate Governance review: a. For single centre, non portfolio research studies meeting the REC requirements for proportionate review, the Trust will apply the same proportionate principles to the Governance checks and approval of the research study. 4.4 RGPAS Committee Sponsorship Review (see Process Map 1) a. RGPAS committee sponsorship review is undertaken prior to submission to a Research Ethics Committee (REC) and all other necessary regulatory bodies. See SOP048 Applying Version 5.0 Review Date: October 2017 Page 5 of 18

for Papworth Sponsorship for guidance on the application procedure to request sponsorship review. 4.4.1 Objectives of the sponsorship review: a. Confirm the Trust has necessary resource to support the research b. Identify any potential risks and agree actions to mitigate any identified risks c. Review all external applications and documentation to regulatory authorities d. Agree whether or not the study is required to be returned to RGPAS for local review. 4.4.2 Minimum document set for sponsorship review: a. Protocol b. Draft of Patient Information Sheet (PIS) where appropriate c. Draft of Informed Consent Form (ICF) where appropriate d. Draft of the IRAS REC application form e. Evidence of peer review or plan for obtaining peer review 4.4.3 Peer review of sponsored studies: a. The level of peer review required is proportionate with the type of research. b. Papworth sponsored research funded by an external grant award will not be required to provide additional evidence of peer or scientific review other than notice of the award. c. For high risk non-ctimps, CTIMPs and non-ce marked device studies (i.e. those that require MHRA approval), peer review must be completed by two external reviewers. d. For student research projects review by the academic supervisor, and/or clinical management group is considered appropriate. A signed R&D or REC form is considered acceptable evidence. e. For all other studies peer review may be requested if concerns are raised at RGPAS. 4.4.4 Outcomes of RGPAS committee sponsorship review: a. The RGPAS committee will either recommend: Version 5.0 Review Date: October 2017 Page 6 of 18

1. Sponsorship agreed to, pending satisfactory completion of any conditions. 2. Sponsorship is declined. b. Following satisfactory completion of any conditions, declaration D2 on the Integrated Research Application System (IRAS) application form is signed by the Clinical Director of R&D or their delegated representative. c. Where sponsorship is declined feedback and advice is provided to the research team. 4.5 RGPAS Committee Local Review (see Process Map 2) a. Where a study has previously been reviewed for sponsorship, it will not be returned to RGPAS for an additional local review, unless: 1. Requested by the RGPAS committee at sponsorship review 2. The study design or conduct is significantly different from that presented at sponsorship review. b. The research officer will submit a study for local review once REC have given a provisional opinion*, the minimum document set is available and sufficient feasibility has been conducted to allow a decision to be made. * unless prior agreement is sought from the research governance team. 4.5.1 Objectives of local review: a. Agree the risk assessment b. Identify any issues that will prevent the study from proceeding at the Trust c. Agree action points to resolve any issues preventing the study proceeding d. Agree the overall project feasibility 4.5.2 Minimum document set for RGPAS Committee Trust Approval Review a. Protocol b. Signed REC form or R&D form c. Patient Information Sheet d. Informed Consent Form e. Draft of Risk assessment. See SOP025: Assessment and Registration of Trust Risk Rating for Research Studies. Version 5.0 Review Date: October 2017 Page 7 of 18

4.5.3 Outcomes of RGPAS Committee Local Review a. The RGPAS committee will either recommend: 1. Trust approval agreed to, in principle, pending full governance review and satisfactory completion of conditions. 2. Trust approval declined. b. Where trust approval is declined feedback and advice is provided to the research team. 4.6 Governance Checks (see Process Map 2) a. The study team or research officer initiates the governance checks by submission of the Valid Research Application (VRA) documents as detailed in 4.6.3. b. The date of submission of documents constituting a VRA will be considered the start date from which performance metrics are calculated. Where a submission is judged to be invalid it will be returned to the research team with a request to resubmit once the invalid aspect has been corrected. 4.6.1 Portfolio Studies a. For portfolio studies the documents are submitted electronically in IRAS. On submission, documents will appear in the NIHR Coordinated System for gaining NHS permission (CSP) database and will be processed following the operating guidelines and guidance notes issued by NIHR. 4.6.2 Non Portfolio Studies a. For non- portfolio studies all documents will be submitted by email to R&DEnquiries@papworth.nhs.uk. 4.6.3 The following documents must be submitted for local trust approval. Signed SSI form Required for Full Governance Review Documents constituting a VRA Required for proportionate governance review CV s of research team Version 5.0 Review Date: October 2017 Page 8 of 18

Localised PIS, ICF Localised GP letter and Letter of Invitation (where applicable) Signed REC form or Signed R&D form REC approval letter All documents approved by REC MHRA Approval letter GCP certificates of research team* Signed Risk Assessment document Authorisation to proceed from affected Directorates and support services Notification that contract and costings agreements are in place, where applicable Notification that MTA agreement or equivalent is in place, where applicable 4.6.4 Investigator suitability a. Suitability of an investigator is assessed and confirmed through submission of an up to date CV (signed and dated within 2 years) and through clinical management approval. b. Failure to provide an up-to-date CV will prevent the investigator participating in the study. c. The clinical directorate in which the investigator sits is responsible for confirming suitability of the investigator to undertake the research in terms of qualifications and experience. d. For instances whereby a directorate has expressed concern with regards to an inexperienced researcher the conduct of their study will be overseen by the medical directorate and managed by recommendation from a risk assessment. Version 5.0 Review Date: October 2017 Page 9 of 18

4.6.5 Authorisations a. All Clinical Directorates and support services impacted by the proposed research are required to assess the impact of the proposed research on clinical activity within their area and give approval for the research to take place. b. Directorate and support service approvals are given on the basis of the information supplied in the SSI form. c. Information provided in the SSI must detail all research procedures and the locations, departments, groups or units at which, or through which, these procedures will be conducted at Papworth Hospital. 4.6.6 GCP training a. Evidence of GCP training is required prior to Trust approval for personnel working on CTIMP or device studies. b. For further guidance see SOP049: GCP Training for Research Staff 4.6.7 Contracts and Finance a. For applicable research studies, the Finance and Contracts manager, or delegate, will notify the Governance team when contracts have been agreed with external parties. Trust approval will not proceed until notification is received. 4.6.8 MTA a. Each study will be assessed to ascertain details of any tissue samples collected during the course of the research. Material Transfer Agreements (MTA) may be required for studies transferring samples to another site in accordance with national legislation and guidelines. b. For studies where samples taken are to be retained and stored at Papworth Hospital beyond the end of the study (and therefore beyond the period of the Research Ethical Approval), the Human Tissue Authority (HTA) regulations will become applicable. At this point samples should be transferred to the tissue bank and further REC approval sought. 4.6.9 Regulatory and ethical approvals a. All regulatory and ethical approvals must be in place prior to commencement of research. Version 5.0 Review Date: October 2017 Page 10 of 18

4.6.10 Ionising radiation a. Each study will be assessed to confirm compliance with the Ionising Radiation (Medical Exposure) Regulations 2000 (IRMER). The radiology representative will highlight any issues at the RGPAS committee local review. Authorisations will be obtained from the clinical director, Radiology, or delegate where the study includes research exposures. 4.7 Regulatory Green Light a. Once all research governance checks have been completed; documentation is in place, and all outstanding issues/queries have been addressed, regulatory green light is authorised by a member of the Research Governance Team. b. Regulatory green light is documented by completion and sign-off of the appropriate regulatory green light checklist. Checklists for sponsored and non-sponsored studies are available. See FRM022 RGL Checklist for Non Papworth Sponsored Studies and FRM023 RGL Checklist for Papworth Sponsored Studies. c. A delegation log of signatories for the regulatory green light checklist is kept in the R&D Unit, recording all qualified staff to undertake review and authorisation by a R&D Manager. Evidence of relevant training is maintained in an individual s training records. 4.8 NHS permission a. No research activities can take place at Papworth until NHS permission has been issued. b. NHS Permission is issued once all checks on the regulatory green light checklist have been completed and the regulatory green light has been authorised c. The decision to issue NHS permission is undertaken on behalf of the Trust by the Clinical Director of R&D or designee on review of all information provided, including the regulatory green light. d. The Chief Investigator or Principal Investigator is notified of NHS permission via a trust approval letter, signed by the Clinical Director of R&D or designee. e. The Trust is not obligated to approve studies, even if the regulatory green light is given e.g. risk to Trust is unacceptable, or compromises recruitment to ongoing studies. f. For CTIMPs a copy of all R&D correspondence to the investigator relating to permissions is copied to pharmacy. g. For Papworth sponsored CTIMPs, if NHS permission is granted, the research governance file is amalgamated with Trial Master File. Version 5.0 Review Date: October 2017 Page 11 of 18

4.9 Withdrawal of NHS permission a. NHS permission is granted on the basis of the information provided to R&D at time of approval. Papworth Hospital NHS Foundation Trust reserves the right to withdraw trust approval should they be made aware of issues which may negatively affect study patients; the trust; the study itself or staff. b. If permission is suspended a full investigation will be undertaken and then a decision made to stop the study or continue. Investigators may only proceed once confirmation in writing from R&D has been received. c. If NHS permission is withdrawn appropriate plans must be documented and agreed with appropriate regulatory authorities to ensure the safety of the patients. 4.10 Performance in Initiating and delivering research a. In accordance with the Plan for Growth March 2011, the Trust will: 1. Measure and publish data on the days elapsing between receipt of a VRA for a clinical trial and the time when the first patient is recruited to the trial, for all clinical trials hosted. 2. Measure and publish data on recruitment to time and target for all commercial trials hosted. b. Further information is available at http://www.nihr.ac.uk/policy-andstandards/performance-in-initiating-and-delivering-research.htm 4.11 Protocol amendments a. All amendments must be submitted to the Research Governance team for review. b. Notification of amendments and submission of documents is via: R&DEnquiries@papworth.nhs.uk c. For amendments to Papworth sponsored studies see SOP037: Amendments to Research Documents of Papworth Sponsored studies post Trust Approval 4.11.1 Substantial amendments a. The following information must be submitted for substantial amendments: 1. Notice of substantial amendment 2. REC approval letter (plus approvals from other applicable regulatory bodies) 3. Electronic copies of all REC approved documents Version 5.0 Review Date: October 2017 Page 12 of 18

b. If it is deemed that the proposed amendment does not affect any changes to the original risk assessment; research s impact on clinical activity, or finance and contracts already in place for the study, then the amendment will be approved via chairman s action outside of the RGPAS meeting and submitted to the next scheduled meeting for information only. c. The Principal Investigator is notified of continuing permission via an amendment approval letter, signed by the senior manager, R&D or delegate. d. Substantial amendments affecting change to risk, clinical activity or finance will be presented to RGPAS committee for review and approval. 4.11.2 Non substantial amendments a. Non substantial amendments will be reviewed and approved via chairman s action outside of the RGPAS meeting and submitted to the next scheduled meeting for information only. b. The Principal Investigator is notified of continuing permission via an amendment approval letter, signed by the senior manager, R&D or delegate. 4.12 Service Evaluations and Research not requiring Ethical Review a. All service evaluations and research deemed as not requiring ethical review (based on REC guidelines) will be reviewed by the R&D Unit and Trust permission granted. b. Documentation required for review: 1. Brief summary of project c. Service evaluations will be circulated for review by the research officers. Trust approval will be issued where two research officers confirm the proposal does not need ethical approval. The decision will be tabled and documented at the next RGPAS meeting. d. Where a decision is not agreed, the proposal will be discussed at the next RGPAS committee meeting. 4.13 Participant Identification Centres (PIC s) a. Where study activities are limited to identifying and /or informing patients or service users of a potential opportunity to participate in research, Papworth is considered to be a PIC. b. The study will be reviewed by the R&D unit. The review will be limited to any issues relating to identifying and informing patients. Version 5.0 Review Date: October 2017 Page 13 of 18

c. Documents required for review: 1. Signed REC form 2. All REC correspondence 3. All REC approved documentation d. Trust permission will be issued confirming the Trust s agreement to act as a PIC. 4.14 Record of Study Documents (see FRM012 Version Control of Trust Approved Documents) a. For each active research study, a record is created and updated by the Research Governance team of version controlled, trust approved, study documents. b. The record provides a single point of reference for the research team of the current and superseded versions of study documents submitted to R&D during the course of the study. The record also includes details of REC approval dates, Trust permission date, and amendment approval dates. 4.15 The following study documents are listed on the version control: 1. Protocol and protocol summaries 2. Information and consent forms 3. Invitation letters and follow up letters 4. GP letters 5. Questionnaires (if version controlled) 6. Instruction manuals (if version controlled) 7. Diary cards 8. NOTE : Investigator brochures and generic questionnaires are not included a. The current version control document is appended to the Trust approval letter and also any subsequent amendment approval letters. 4.16 RGPAS 4.16.1 The role of RGPAS is to; a. Ensure that the research approvals process within the Trust adheres to the Research Governance Framework (Department of Health: 2005 2nd edition) and all applicable legislation. Version 5.0 Review Date: October 2017 Page 14 of 18

b. Ensure all clinical trials of investigational medicinal products (CTIMPs) and trials of non-ce devices comply with all relevant legislation including the Medicines for Human Use (Clinical Trials) Regulations and all applicable amendments before a study commences. c. For sponsored studies, ensure The Trust is able and agrees to fulfil the responsibilities of sponsorship. d. Ensure a study is feasible to be undertaken within the Trust; i.e. appropriately resourced, risk assessed. e. Issue the regulatory green light for NHS permission to be granted. f. Review and approve service evaluations and other projects not requiring ethical or other regulatory approval. 4.16.2 RGPAS committee Membership a. To address all aspects of research activity within the Trust, the RGPAS committee is comprised of the following regular attendees, plus adhoc attendees as invited by the chair. 1. The R&D Governance Coordinator (chair) 2. An R&D Manager 3. The Research Officers 4. The Clinical Trials pharmacy representative 5. The Radiology representative b. To ensure the meeting has the necessary quorum, a total of 5 members must be present with one R&D Manager and at least two Research Officers. The remaining quota can comprise of any members of the committee. c. Representatives from radiology and pharmacy will attend if relevant research studies have been timetabled for discussion. d. If absent the chair will nominate a deputy chair. e. RGPAS meetings are usually held fortnightly and meeting dates are available from the R&D Unit. f. In the event that any of the above personnel are unable to attend the RGPAS meeting in person, then comments and feedback in writing will be accepted and addressed during the meeting. Comments fed back by members are counted towards the quorum. g. Researchers are invited to attend RGPAS to discuss their research and answer any questions the committee may have. Version 5.0 Review Date: October 2017 Page 15 of 18

5 Risk Management / Liability / Monitoring & Audit a. The R&D SOP Committee will ensure that this SOP and any future changes to this document are adequately disseminated. b. The R&D Department will monitor adherence to this SOP via the routine audit and monitoring of individual clinical trials and the Trust s auditors will monitor this SOP as part of their audit of Research Governance. From time to time, the SOP may also be inspected by external regulatory agencies (e.g. Care Quality Commission, Medicines and Healthcare Regulatory Agency). c. In exceptional circumstances it might be necessary to deviate from this SOP for which written approval of the Senior R&D Manager should be gained before any action is taken. SOP deviations should be recorded including details of alternative procedures followed and filed in the Investigator and Sponsor Master File. d. The Research and Development Directorate is responsible for the ratification of this procedure. Version 5.0 Review Date: October 2017 Page 16 of 18

Further Document Information Approved by: Management/Clinical Directorate Group Approval date: (this version) Ratified by Board of Directors/ Committee of the Board of Directors: Date: This document supports: Standards and legislation Research and Development Directorate 28 October 2014 STET N/A Medicines for Human Use (Clinical Trials) Regulations 2004 and all associated amendments. Research Governance Framework for Health and Social Care (2005) Trust Research Policy SOP025: Assessment and Registration of Trust Risk Rating for Research Studies SOP037: Amendments to Research Documents of Papworth Sponsored studies post Trust Approval Key related documents: SOP048: Applying for Papworth Sponsorship SOP049: GCP Training for Research Staff FRM022 RGL Checklist for Non Papworth Sponsored Studies FRM023 RGL Checklist for Papworth Sponsored Studies Equality Impact Assessment: Does this document impact on any of the following groups? If YES, state positive or negative, complete Equality Impact Assessment Form available in Disability Equality Scheme document DN192 and attach. Groups Disability Race Gender Age Sexual orientation Religious & belief Other Yes/No Positive/Negative Review date: October 2017 Version Control Version 5.0 Review Date: October 2017 Page 17 of 18

Version Date effective Valid to Approved by Date of approval 1.0 2.0 3.0 4.0 5 th June 2013 Mar 2016 RDD ( Chairman s action) 7 th May 2013 5.0 25 Nov 2014 Oct 2017 RDD 14 Nov 2014 Version 5.0 Review Date: October 2017 Page 18 of 18