Jill Peacock RM&G Manager DEMYSTIFYING R&D APPROVALS Content: • What is NHS Management Permission and why do I need it? • What happens here at NUTH FT? • The risk assessment step-by-step • Where does CSP fit in? • What you can do to help get approval quicker • R&D figures • Questions??? WHAT IS NHS MANAGEMENT PERMISSION? NHS Management Permission is the approval given by an NHS organisation for the conduct of research that involves their NHS patients, the patient’s data, tissues or that organisation’s resources. Also known as: •R&D Approval •NHS Permissions •NHS R&D Management Permission •Research Governance Approval •Ethics & Governance for university projects WHY DO WE HAVE R&D APPROVAL? As detailed in section 3.10 of the Research Governance Framework 1: It is the responsibility of organisations providing health or social care in England to be aware of all research undertaken in their organisation, or involving participants, organs, tissue or data obtained through the organisation. This is achieved by the registration of research activity through one central department (Trust R&D) who coordinate the review and issuing of approval for this research activity on behalf of the Trust. Many departments are involved in the granting of NHS Management Permission. THE NUTH FT PROCESS THE NUTH FT PROCESS - SUBMISSION • Documents are submitted either electronically to the R&D generic inbox (Trust.R&[email protected]) or received through CSP. • Project is assigned to a processor. • Processor goes through documents against submission checklist and decides if a full submission has been received. • If not processor contacts study team to request missing documents and inform them of the deadline for submission. • Once full submission received R&D confirm that study is going to next R&D Approvals Committee meeting and processor completes data entry sheet & projects for agenda spreadsheet. The NUTH FT PROCESS - SUBMISSION Document Attached Research Support Form (V5 March 2011) – this form Evidence of funding (eg, award letter, details of cost centre etc). Please note, if your award is being processed through Newcastle University, evidence of funding will already be available to us in the Joint Research Office – please ensure you have provided your BH or RES number A breakdown of costs at this site in addition to any costings spreadsheet you may have (eg, from the Research Platforms, Industry Costing Template etc.) Latest study protocol with version number and date. Latest Participant Information Sheet and Informed Consent Form with version number and date. NHS R&D Form (generated via IRAS and submitted as an XML file AND a PDF file) – see guidance in IRAS about how to save XML files. This must be signed or electronically authorised by the chief investigator and sponsor (plus academic supervisor if a student project) PDF XML SSI Form (generated via IRAS and submitted as a PDF file AND XML) This must be signed or electronically authorised by the investigator at this site PDF XML CV (2 page) of the main investigator at this site Study agreement/contract for ALL commercial projects (at least in draft). This should be the nationally recognised model agreement between the NHS and industry(see link below) and should include a completed financial schedule http://www.ukcrc.org/regulationgovernance/modelagreements.aspx) Favourable opinion from NHS REC Notice of Acceptance letter from MHRA (if already granted) Caldicott approval (if already granted) Other (eg, NIGB, IRMER, ARSAC if required): Awaited THE NUTH FT PROCESS – DRAFT RISK ASSESSMENT • Assigned processor drafts risk assessment prior to R&D Approvals Committee Meeting. • Proposed Clinical Trial Agreements are normally reviewed at this time. • If able to the processor may contact study team to give them pre-warning of what has been identified as being outstanding HOWEVER: • Processor cannot pre-empt all of the committee’s comments THE NUTH FT PROCESS – COMMITTEE MEETING The R&D Approvals Committee meets approximately every fortnight to review submissions for NHS Management Permission. Committee members include: •Chair of R&D Approvals Committee OR •Clinical Director of R&D •Head of the JRO •Research Governance Manager •Representatives from finance, pharmacy, radiology, theatres •Representative of Newcastle Clinical Trials Unit •NIHR Operations Manager •Research Matron •RM&G Managers and R&D Facilitators THE NUTH FT PROCESS – FINAL RISK ASSESSMENT Following the meeting the risk assessment is finalised and issued to the Principal Investigator (PI), Study Coordinator/Research Nurse and any support department with approval outstanding. We aim to send this within 1 week of the meeting. The accompanying email highlights the outstanding items and we chase for these until everything is resolved. If an amendment is submitted while the study is undergoing review then this will also be reviewed. THE R&D RISK ASSESSMENT A risk assessment is performed for every study that goes to committee and looks at: Finance & Support Departments Scientific Validity Insurance/Indemnity Study Agreements Publicity Risk to the Trust Ethics & Regulatory Approvals Data/NIGB Tissue/IRMER/ARSAC Site Specific Assessment Monitoring Arrangements Pharmacy Details FINANCE & SUPPORT DEPARTMENTS All research projects have to demonstrate financial probity, i.e. there is enough funding to perform the study. This is especially pertinent for industry-sponsored studies as the NHS will not financially subsidise commercial research. Trust finance require a cost for the conduct of the study at NUTH FT and proof of funding to cover that cost (examples on next slide). The support departments review studies to ensure that there is staff and capacity to perform the required assessments. They also confirm that the proposed funds to cover the cost of these assessments is adequate. FINANCE DOCUMENTATION Examples of costings: • Local costing spreadsheet • NIHR Industry costing template with accompanying email from PI that this accurately reflects the costs at NUTH FT • Blue form for studies where the award is administered through Newcastle University • Confirmation from Research Team Lead that all costs are covered by NHS Service Support (for NIHR Portfolio studies) Examples of proof of funding: • Clinical Trial Agreement with completed financial appendix • Grant award letter • An account number for Own Account studies • Letter/email from the Clinical Director to confirm the directorate will cover any incidental costs SCIENTIFIC VALIDITY All studies are required to demonstrate their scientific validity through a positive peer review. It is the responsibility of the sponsor to ensure that this is done. Commercial sponsors usually perform peer review in house; non-commercial studies with large funders are peer reviewed as part of the funding award process; Newcastle University academic studies are usually peer reviewed by the University’s Board of Studies. For studies where NUTH FT are sponsor and no other form of scientific review has been performed, peer review is arranged via Trust R&D. The process is anonymous so PIs are not informed of who their reviewer is. Reviewers are given 3 weeks to perform the review before they are chased. INSURANCE & INDEMNITY All studies are required to have appropriate insurance and indemnity in place in case of harm to the participants. Cover is required for 3 distinct areas: Study Management & Conduct – cover is the responsibility of the sponsor; if the sponsor is an NHS Organisation then the NHS Clinical Negligence Scheme provides cover for negligent harm only. Study Design – cover is the responsibility of the SUBSTANTIVE employer of the protocol author(s). An honorary contract does NOT cover protocol design. The same applies for NHS employees who write protocols as part of an academic qualification. This activity falls outside of their substantive contract so the relevant academic institution is required to provide indemnity. CONTRACTS/CLINICAL TRIAL AGREEMENTS Contracts/Clinical Trial Agreements (CTAg) are required for: •Clinical Trials of Investigational Medicinal Products (CTIMPs) •All commercially sponsored studies •Studies where there is a transfer of money or supplies •Complex studies that don’t fall under the above It is the responsibility of R&D to negotiate and agree contracts with the sponsor on behalf of the Trust and all agreements need to be signed by the official Trust signatory (i.e. they cannot be signed by the PI on behalf of the Trust). Partially executed agreements must not be requested until feedback is given by R&D. CONTRACTS/CLINICAL TRIAL AGREEMENTS Standard items that appear in every agreement: • The legal name & address of the Trust is: The Newcastle upon Tyne Hospitals NHS Foundation Trust of Freeman Hospital, Freeman Road, High Heaton, Newcastle upon Tyne, NE7 7DN. • Notices to the Trust go to: Amanda Tortice, Head of the Joint Research Office, Level 6 Leazes Wing, Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne NE1 4LP. • The official Trust signatory is Mr Steven Reed, Trust Secretary. • The R&D set-up fee for commercially sponsored studies is £1000 for agreements that follow the model template and £1500 for agreements with changes/nonstandard agreements ETHICS & REGULATORY APPROVALS R&D approval cannot be granted until all other approvals are in place and all approvals are co-dependent on the other being in place for them to be valid. Ethics We require all of the REC correspondence from first opinion (provisional/conditional/favourable), any responses from the CI to the REC and all amendment notifications and approvals/acknowledgments from the REC. MHRA CTIMP We require a copy of the Clinical Trial Authorisation and any subsequent amendment acknowledgments. MHRA Device We require a copy of the Notice of No Objection and any subsequent amendment acknowledgments. CALDICOTT & NIGB Where a research project involves the collection or transfer of person identifiable data outside of the organisation the researcher must obtain Caldicott approval. Each and every research project that is submitted for R&D approval will be requested to obtain Caldicott approval. If the researcher feels this is not necessary then all queries are forwarded to the Information Governance Department for final decision. All research projects that involve persons outside of a patient’s clinical care team accessing their person identifiable data without seeking their consent will need to obtain approval from the National Information Governance Board for Health & Social Care (NIGB). Applications forms are completed through IRAS with hard copies submitted to the board. Please note that there are only 2 further meetings in 2012 and applications for NIGB must be submitted approximately 6 weeks in advance. IRMER & ARSAC The Ionising Radiation (Medical Exposure) Regulations 2000 (IRMER) apply to studies utilising ionising radiation (CT scans, x-ray). Each and every site involved in a study must have had an IRMER review performed by a local radiation expert. Our expert is still Dr John Kotre. If the local radiation assessment differs significantly to that performed by the sponsor then the sponsor needs to be made aware as a substantial amendment to REC may be required. Administration of Radioactive Substances Advisory Committee (ARSAC) review applications for an ARSAC Certificate. ARSAC Certificates are required by law for studies involving radioactive substances (MUGA scans, bone scans, PET scans) outside of routine clinical practice. An ARSAC certificate is site specific so if a study is ran at RVI and FRH two certificates are required. They are valid for 5 years only. TISSUE A thorough review of the arrangements is performed for all studies obtaining new or using existing tissue samples. We look at what is being taken, where it is being stored, how long it is being stored for and who will have custody of it. If tissue samples are coming from a bank or going to a bank, a Material Transfer Agreement (MTA) will be needed. MTAs are arranged between the provider and the receiver of the tissue and documents the responsibilities for obtaining, processing, shipment and custody of the samples in line with the Human Tissue Act. Samples moving from NUTH FT to Newcastle University are covered by an umbrella Service Level Agreement (SLA) so individual MTAs are not required. In order for a research project to be registered as being covered by the SLA, the SLA Tissue Monitoring Form needs to be completed and returned to R&D and the Tissue QA Manager. SLA Monitoring Form SITE SPECIFIC ASSESSMENT The responsibility for performing the Site Specific Assessment (SSA) transferred from RECs to Trust R&Ds in April 2009. SSA is performed as part of the study review by the R&D Approvals Committee. The Committee assess the suitability of the PI, members of the study team and the proposed facilities for conducting the study. The Site Specific Information form and PI CV are used to do this. Proposed PIs at NUTH FT: Need to have a substantive or honorary clinical contract with NUTH FT Have to be of consultant level or equivalent Have to be a member of a professional healthcare body MONITORING The monitoring arrangements for CTIMP studies are reviewed. If the CTIMP is to be self monitored i.e. the local team will complete monitoring forms and send them back to the sponsor, this has resource implications for the research team and pharmacy department which need to be taken into consideration and costed for appropriately. If the CTIMP is sponsored by NUTH FT it is a standard condition of sponsorship that the study be managed and monitored by a UKCRC registered Clinical Trials Unit. If the study utilises remote monitoring i.e. data and Case Report Forms are sent off to the sponsor, then the team need to be aware that all directly identifiable information must be removed (hospital number/patient name) and this arrangement must have received Caldicott approval. PHARMACY In addition to examining capacity and staffing for performing the study, pharmacy also look at the IMP management and storage arrangements, blinding arrangements and the break blind procedure, out of hours requirements and exit strategy. IMP storage - if the IMP is to be stored outside of pharmacy then a risk assessment needs to be performed by pharmacy to ensure the storage facility meets regulatory requirements, e.g. that the temperature of the facility will be monitored and that reconciliation will be performed correctly. Exit strategy – will participants have access to the IMP when the study ends and is this clear. There are frequent issues with sponsors not detailing exit strategies clearly in Participant Information Sheets. The Trust has been affected in the past with studies where treatment was withdrawn but the participants were benefitting so the Trust ended up covering the cost of the treatment regimens. THE NUTH FT PROCESS - APPROVAL Once all outstanding items are resolved, the project can go for approval. The R&D file must be signed off by the Clinical Director of R&D/Chair of the R&D Approvals Committee and the signatory for the NHS Management Permission letter. Contracts are sent to the Trust Signatory for sign off while the NHS Management Permission letter is drafted. The NHS Management Permission letter is printed and signed off and issued to the PI, Study Coordinator/Research Nurse, Directorate Manager, Chief Investigator (if not PI), Trust Finance, Trust Pharmacy (if applicable) and Sponsor’s Representative (if not NUTH FT). This is the ONLY form of NHS Permission/R&D Approval given. If you don’t have this you don’t have approval and cannot start the study! WHERE DOES CSP FIT IN? The NIHR Coordinated System for gaining NHS Permission (CSP) is the governance system for studies applying for adoption to the NIHR Portfolio. Studies applying for adoption HAVE to obtain their R&D Approval through CSP or the study will be rejected from the Portfolio. CSP studies are processed the same as non-CSP studies i.e. they go to committee, a risk assessment is prepared and outstanding items are resolved prior to approval. However, we are measured on how quickly we approve our CSP projects against the 30 day national target. As such, we request that PIs/Trial Coordinators do not electronically authorise and submit their SSI form to CSP until they are ready to submit to R&D to ensure a fair and accurate approval time. Please drop the relevant R&D processor a quick email just to say that it has been submitted. WHAT CAN I DO TO GET MY APPROVAL QUICKER? When making a submission there are a few things you can do to aid the process: • Ensure that there is a local costing and proof of funding for the study and that the funds are greater than the cost. • If the study requires NIGB approval, IRMER review or ARSAC get these processes started early. • Clinical Trial Agreements – ensure that the sponsor knows what the standard bits are particularly fees for commercial sponsors. Also try to obtain an unprotected, word version of the agreement to ease review. • Encourage the PI to do their part: signing/electronically authorising the SSI form, signing the PI responsibility documents and answering any queries from the risk assessment promptly. R&D FIGURES NUTH FT topped the NIHR CRN 2011-2012 Activity table with 404 active NIHR Portfolio studies (the next Trust had 367) Number of projects approved* 280 (& 1 rejection) Number of current active projects ~800 Number of amendments reviewed* 1071 Number of requests for sponsorship reviewed* 81 Number of audits performed* 32 * Between 1st April 2011 – 31st March 2012 R&D TEAM Head of the Joint Research Office – Amanda Tortice Research Governance Manager – Susan Ridge R&D Receptionist/Data Clerk – Richard Joyce Studies conducted in RVI & Community Services Research Management & Governance Manager – Sean Scott R&D Facilitator – to be appointed Research Secretary – to be appointed R&D TEAM Studies conducted in NCCC, CARU, ICfL, Diabetes & Paediatric Oncology Research Management & Governance Manager – Andrew Johnston R&D Facilitator – Manju Agarwal & to be appointed Research Secretary – Angela Fallows Studies conducted in FRH & Dental Hospital Research Management & Governance Manager – Jill Peacock R&D Facilitator – Jenn Walker Research Secretary – Mary Crane QUESTIONS?