STANDARD OPERATING PROCEDURE

Transcription

1 STANDARD OPERATING PROCEDURE Title Reference Number Sponsorship SOP-RES-001 Version Number 3 Issue Date 29 th Sep 2016 Effective Date 10 th Nov 2016 Review Date 10 th Nov 2018 Author(s) Reviewer(s) Teresa O Leary, Head of Regulatory Compliance Joanne Thornhill, Research Project Manager Team Leader Authorisation (Original signatures are retained by Research & Innovation) Dr Stephen Ryder Director of Research & Innovation Dr Stephen Fowlie Medical Director 01 st Aug nd Sep 2016 USERS OF THIS STANDARD OPERATING PROCEDURE MUST REFER TO TO ENSURE THE MOST CURRENT VERSION IS BEING USED

2 Page 2 of Document History Version Issue Date Reason for Change Number 1 22 nd April 2014 Original version. It replaces SOP Apr 2016 HRA process updates and biennial review 3 29 th Sep 2016 Update based on SOP_RES_002 changes

3 Page 3 of Introduction The sponsor is the individual, company, institution or organisation, which takes on ultimate responsibility for the initiation, management (or arranging the initiation and management) and/or financing (or arranging the financing) for that research. The sponsor takes primary responsibility for ensuring that the design of the study meets appropriate standards and that arrangements are in place to ensure appropriate conduct and reporting. In some cases, there may be joint-/co-sponsorship arrangements in place whereby more than one individual, company, institution or organisation takes on sponsorship responsibilities. If so, one body should be nominated as the lead sponsor and an agreement should be provided describing the responsibilities of each sponsor. Joint-/co-sponsorship is an arrangement only recognised in the UK and is therefore not applicable to multi-national studies. Whilst the Research Governance Framework for Health and Social Care: Second edition, 2005 (RGF) and The Medicines for Human Use (Clinical Trials) Regulations 2004 allow for individuals to act as sponsor, Nottingham University Hospitals NHS Trust (NUH) does not permit this. 3. Purpose and Scope This standard operating procedure (SOP) applies to any research study where NUH is requested to act as sponsor or joint-/co-sponsor. NUH may act as sponsor or joint-/cosponsor if at least one of the following criteria are met: i. NUH is the main funder of the research or hold grant funding ii. the chief investigator (CI) holds a substantive or honorary contract with NUH; iii. the research is being undertaken by one of the Nottingham Biomedical Research Units; iv. NUH is the leading care organisation where the research is to take place. If research is being undertaken at NUH for an educational qualification the awarding institution (e.g. university) should act as sponsor. If any of the above criteria are met and the research is being undertaken at NUH for an educational qualification the awarding institution should act as sponsor in the first instance, however NUH may agree to act as sponsor; this will be assessed on an individual basis. Sponsorship is not guaranteed if any or all of the above criteria are met. NUH will sponsor studies which are of high scientific worth and will be of benefit to patients and/or the Trust.

4 Page 4 of 15 NUH may decline sponsorship if there is evidence that there are insufficient facilities and/or inexperienced/unqualified personnel conducting the research, or if there is insufficient financial resources available for the safe and effective conduct of the research. This SOP does not apply to research that is not sponsored by NUH. 4. Responsibilities Chief Investigator Ensure that NUH is aware of the research proposal and accepts sponsor responsibilities prior to submitting any other application (e.g. for grant funding, HRA Approval including research ethics committee (REC) favourable opinion, clinical trial authorisation (CTA)). Not agree any funding amount prior to requesting sponsorship authorisation. If funding is secured prior to requesting sponsorship authorisation there may be insufficient funds available to cover the sponsor management costs and the request for sponsorship may be rejected.

5 Page 5 of 15 Sponsor (fulfilled by the Research and Innovation (R&I) Department on behalf of NUH). For grant funded research; a letter of Sponsorship in Principle is agreed to and costed as a part of the application to the funding body, this letter is issued by R&I. The R&I Administrator will register sponsorship requests in Documas and prepare a study file of submitted documentation. R&I Research Project Managers (RPMs) will assess all sponsorship requests and facilitate sponsorship authorisation. R&I personnel representative of regulatory compliance, quality assurance, finance, intellectual property (IP) and grants will provide input into sponsorship decision-making where appropriate. The Director or Deputy Director of R&I will authorise NUH sponsorship. 5. Definitions CI CMD CRF CTA CTIMP Documas HRA IB IP ICH-GCP IMP IMPD IRAS ISF ISO NHS NUH PIS QA R&D Chief Investigator Clinical Investigation of a Medical Device Case Report Form Clinical Trial Authorisation Clinical Trial of an Investigational Medicinal Product A document management system to assist with the management, control and governance of the research and ethics processes covering research and development projects Health Research Authority Investigators Brochure Intellectual Property International Conference on Harmonisation Guidelines for Good Clinical Practice Investigational Medicinal Product Investigational Medicinal Product Dossier Integrated Research Application System Investigator Site File International Organization for Standardization National Health Service Nottingham University Hospitals NHS Trust Participant Information Sheet Quality Assurance Research and Development, within IRAS this is the Research and Development application form

6 Page 6 of 15 R&I REC RGF RPM SmPC SOP SSI TMF Research and Innovation Research Ethics Committee Research Governance Framework for Health and Social Care Research Project Manager Summary of Product Characteristics Standard Operating Procedure Site Specific Information Trial Master File 6. Procedure The sponsorship review and authorisation process varies depending on the nature and complexity of the study. Typically clinical trials of investigational medicinal products (CTIMPs) or clinical investigations of medical devices (CMDs) (or combinations thereof) require a more detailed sponsorship review to be undertaken, whereas studies not defined as CTIMPs or CMDs require a less detailed sponsorship review. See Appendix 1 for an overview of the sponsorship process. 6.1 Grant/Funded Research A letter of Sponsorship in Principle is agreed to and costed as a part of the application to the grant/funding body, this letter is issued by R&I Awards Team. The Sponsorship in Principle is agreed between the respective R&I parties, IP, compliance, awards and contracts. During the funding /grant application stage, where possible a sponsorship request form should be completed by CI and ed to RDAPPL@nuh.nhs.uk. This is to provide sufficient information to the compliance team (RPM) prior formal sponsor processing. 6.2 Request for NUH Sponsorship The CI must submit all documentation as listed in Appendix 2 to RDAPPL@nuh.nhs.uk. Upfront provision of accurate documentation and information will reduce the time taken for R&I to complete the sponsorship review and obtain sponsorship authorisation. The R&I Administrator will register the sponsorship request in Documas, confirmation of receipt to the CI and prepare a file of the documentation for review. The R&I Administrator will send the file to the Research Project Manager Team Lead for allocation to a Research Project Manager (RPM). Once allocated the RPM will commence a sponsorship review.

7 Page 7 of Sponsorship Review Feasibility and Risk Assessment The RPM will perform an initial feasibility and facilitate an initial risk assessment (as per SOP-RES-002 Risk Assessment) and document the outcome on the Sponsorship Review form (TAFR00101). If any documentation is missing or further information/clarification is required the RPM will contact the CI. If the study is feasible but requires a risk assessment the RPM will arrange a sponsorship panel meeting (see 6.3.3). Studies that automatically require a risk assessment and therefore a sponsorship panel meeting are CTIMPs, CMDs and CTIMP/CMD combination studies. If the study is feasible but does not require a risk assessment the RPM will continue the sponsorship review and facilitate obtaining the sponsorship authorisation. If the study is not feasible the RPM will notify the CI giving reasons why. The RPM will support the CI to address the feasibility issues should the CI wish to resubmit the sponsorship request. The RPM will scrutinise how personal data will be stored and used. Where systems (such as electronic software, access databases or excel spreadsheets) differ to an existing process or service, or a new process, or information asset is introduced that is likely to involve a new use or significantly changes the way in which personal data is handled the RPM will complete a privacy impact assessment in accordance with NUH Information Security and Risk Policy (GG/INF/002). This does not apply where demographic information of consented participants is stored securely for the purposes of a study, but applies to storage and transfer of personal clinical information Statement of Activities and Schedule of Events For non-commercial studies, a Statement of Activities (SOA) and Schedule of Events SAE) are required for HRA Approval. Guidance on completion of the SOA and SOE are provided within the HRA templates: In general, the SOA require information relating finance, material transfer provisions and confidentiality, data protection and freedom of information. The SOE requires information relating to: - Study Set-Up, Study Monitoring, Study Close-Down - Consent Procedures, Laboratory Tests and Investigations

8 Page 8 of 15 - Medical Exposure / Imaging Tests and Investigations - Pharmacy, Interventions (clinical), Interventions (non-clinical), Other Procedures / Activities The SOA and SOE are prepared by the RPM in collaboration with CI and reviewed by finance, support dept. contracts (if required) and performance teams. For participating organisations, the SOA & SOE may replace a site agreement or model non-commercial agreement (mnca). This will be study dependant and must be agreed with the R&I contracts team. Statement of Activities to replaces mnca when: - non-commercial study - non-interventional e.g. outside top 4 IRAS category Sponsorship Review Meeting Depending on the risk of the study the RPM may initiate a sponsorship review meeting to review the study feasibility and risks with the key stakeholders. The RPM will confirm who is required to attend the sponsorship review meeting and provide members with study documentation in advance of the meeting. The RPM will schedule the sponsorship review meeting to take place as soon as the appropriate members are available to attend. Members will include some or all of the following (additional personnel may attend if requested by the sponsor or the CI): i. RPM required; ii. CI required; iii. Head of Regulatory Compliance (depending on study type/risk); iv. support department representative (i.e. pharmacist, laboratory manager, radiologist) required if relevant for the study. The RPM will verify if the sponsorship review meeting may be linked with any funding application or finance meeting taking place so that R&I finance, grants and/or IP staff may also attend. During the sponsorship review meeting the feasibility and risk assessments will be reviewed in addition some or all of the following will be discussed (additional items may be discussed if relevant for the study): i. purpose and validity of the research; ii. research design and participant involvement; iii. key milestones and timelines; iv. resources and facilities required to conduct the research, including personnel, departments and additional sites; v. considerations for external service providers or vendors; vi. Investigational medicinal product (IMP) and/or medical device, including safety;

9 Page 9 of 15 vii. CI and sponsor responsibilities; viii. vendor management requirements ix. contracts and insurance/indemnity; x. data management requirements xi. statement of activities and schedule of events xii. financial arrangements and sponsor fees. The RPM will document the sponsorship review meeting on the Sponsorship Review form (TAFR00101) (where required) The Head of Regulatory Compliance (HRC) will ensure that the risk assessment is accurately completed, pharmacovigilance, monitoring and audit arrangements for the study are satisfactory, external service providers and vendors are assessed approved (if required), additional sites are qualified and the sponsor management costs are agreed with R&I finance. 6.4 Sponsorship Authorisation Once the sponsorship review has been completed the RPM will request sponsorship authorisation from the Director or Deputy Director of R&I. There are two types of sponsorship authorisation: i. Provisional Sponsorship Authorisation is granted to allow the CI to allow queries to be addressed and to enable contract negotiation (if required). The CI is not permitted to submit applications for HRA Approval (including REC favourable opinion) and / or CTA with only provisional sponsorship authorisation; ii. Sponsorship Authorisation is granted when NUH is satisfied all study and sponsor arrangements are in place and study documentation has been finalised. This authorisation allows the CI to submit an application for the HRA Approval (including REC favourable opinion), to the MHRA for Clinical Trials Authorisation (CTA). NUH agreement to act as sponsor is not approval for the study and is conditional on full HRA approval being gained through the approval processes (refer to SOP-RES-009 Applications and Approvals) and where required a CTA Provisional Sponsorship Authorisation If the sponsorship review has been completed but some sponsorship criteria has not yet been fulfilled (i.e. sponsor management fees being dependent on a funding application

10 Page 10 of 15 being approved) the RPM will request Provisional Sponsorship Authorisation (TAFR00102) and provide this to the CI. The CI should submit all outstanding and/or follow up information to R&I as soon as it becomes available to request sponsorship authorisation. The CI should contact R&I or the RPM who performed the sponsorship review with any queries about how to obtain sponsorship authorisation Sponsorship Authorisation If the sponsorship review has been completed and all sponsorship criteria (as defined in the Sponsorship Review form (TAFR00101)) has been fulfilled the RPM will request Sponsorship Authorisation. This is granted via Director or Deputy Director of R&I signature (wet or electronic signature) on the Integrated Research Application System (IRAS) form. If the study was previously given provisional sponsorship authorisation the RPM will confirm that all sponsorship criteria (as defined in the Sponsorship Review form (TAFR00101)) has been fulfilled the RPM will request sponsorship authorisation. Once sponsor authorisation has been granted the next step is to apply for HRA Approval, refer to the Applications and Approvals procedure (SOP_RES_009). 6.5 Sponsorship Rejection and Withdrawal NUH may decline to sponsor a study, or may withdraw sponsorship if any of the following become known at any time. This list is not exhaustive: i. the research design is not worthwhile, of high scientific quality or good value for money; ii. the research is unethical or individuals or organisations are at risk; iii. there are inadequate resources, facilities, expertise and support to deliver the research safely and successfully; iv. there is lack of research management, monitoring and auditing allocated; v. relevant contracts are not in place; vi. the appropriate research approvals are not obtained; vii. the research is not compliant with applicable regulations (e.g. RGF, International Conference on Harmonisation Guidelines for Good Clinical Practice (ICH-GCP), Clinical Trials Regulations, Medical Devices Regulations, ISO 14155); viii. there is insufficient finance available. R&I will notify the CI in writing, giving reasons, if sponsorship is rejected or withdrawn.

11 Page 11 of 15 If the research has already received a HRA Approval or CTA and sponsorship is withdrawn R&I will notify the relevant bodies in accordance with SOP-RES-025 End of Study Notification and Premature Discontinuation of a Study. 6.6 Joint-/Co-Sponsorship and Delegated Sponsor Responsibilities NUH may act as joint-/co-sponsor with another organisation, such as another NHS Trust. Specific sponsor responsibilities may be delegated to any other individual (e.g. CI) or organisation (e.g. Clinical Trials Unit) that is willing and able to accept them. Responsibilities must be formally agreed and documented (refer to SOP-RES-004 Contracts Management and Insurance/Indemnity). The CI must consider if joint-/co-sponsorship or study management by an external service provider is required as soon as possible to ensure appropriate financial arrangements are available. Appendix 3 summarises NUH sponsorship duties and responsibilities which may be retained or delegated. 6.7 Sponsor Management Costs Sponsor management activities (such as monitoring, pharmacovigilance, IP management) must be appropriately financed for the duration of the study. There is no fixed cost for sponsor management; this will be priced on an individual basis for studies funded by commercial organisations and grants. The following will not incur sponsor management costs: i. Internally funded research (i.e. by a Directorate); ii. Solely Biomedical Research Unit funded studies; iii. Pump Priming or NUH Charity funded research; or iv. Student research.

12 Page 12 of References and Associated Documents Research Governance Framework for Health and Social Care: Second Edition, 2005 The Medicines for Human Use (Clinical Trials) Regulations 2004 and subsequent amendments International Conference on Harmonisation Guidelines for Good Clinical Practice E6 (R1) The Medical Devices Regulations 2002 and subsequent amendments ISO Clinical Investigation of Medical Devices for Human Subjects GG/INF/002 SOP-RES-002 SOP-RES-004 SOP-RES-006 SOP-RES-007 SOP-RES-008 SOP-RES-009 SOP-RES-025 TAFR00101 TAFR00102 Information Security and Risk Policy Risk Assessment Contracts Management and Insurance/Indemnity Local Assess, Arrange and Confirm Process Study Protocols and Documents Case Report Forms HRA and MHRA Application Process End of Study Notification and Premature Discontinuation of a Study Sponsorship Review Provisional Sponsorship Authorisation 8. Appendices

13 Version 2 Effective Date: 26 May 2016 Page 13 of 15 Appendix 1. NUH R&I Sponsorship Process

14 Version 2 Effective Date: 26 May 2016 Page 14 of 15 Appendix 2. Sponsorship Request Documentation This table lists the minimum documentation required to be submitted to R&I for sponsorship request by study-type: Study-Type CTIMP CMD Other Document Protocol or Clinical Investigation Plan Y * Y * Y * Independent peer review Y^ Y^ Y^ Statistical review Y Y Y Evidence of research team qualifications and training (e.g. CV and GCP certificate) Y Y Y Case Report Form (CRF) Y *P Y *P Y *P Patient Information Sheet (PIS) Y *P Y *P Y *P Consent form Y *P Y *P Y *P Other (i.e. participant ID card, participant diary, questionnaire, advertisement, GP letter) Y *P Y *P Y *P Evidence of support department authorisation Y Y Y Summary of product characteristics (SmPC), Investigators Brochure (IB) and/or Investigational Y Y Y medicinal product dossier (IMPD) Device technical specification N/A Y N/A IRAS form (Research and Development (R&D), Site Specific Information (SSI)) Y *P Y *P Y *P Evidence of financing Y P Y P Y P Y = Document required to be submitted (may be N/A for some studies) * = Draft document accepted initially, but this should be final draft in order to obtain sponsorship authorisation ^ = Required if not performed by funding body P = If requesting provisional sponsorship authorisation in order to apply for funding this document may be provided after grant award, however it is required as a criteria for obtaining sponsorship authorisation N/A = Not applicable For further guidance on protocols and other research documents refer to SOP-RES-007 Study Protocols and Documents and SOP-RES-008 Case Report Forms.

15 Version 2 Effective Date: 26 May 2016 Page 15 of 15 Appendix 3. Sponsorship Duties and Responsibilities Responsibilities and Duties Retained The following areas of sponsorship will not be transferred to another organisation and will be operationally undertaken by R&I unless otherwise agreed and documented. Procedures are described in R&I SOPs: i. QA, including audit; ii. monitoring, including source data verification; iii. record keeping (sponsor) including set up and maintenance of the Trial Master File (TMF) and archiving; iv. provision of indemnity/insurance; v. confirmation that appropriate finance is in place for the duration of a study; vi. pharmacovigilance; vii. archiving; The following areas of sponsorship will not be transferred to another organisation and will be operationally undertaken by investigators, or designates, unless otherwise agreed and documented. Procedures are described in R&I SOPs: i. protocol and documentation design; ii. study report preparation; iii. record keeping (investigator), including set up and maintenance of ISF. The wider conduct of research by investigators is described in R&I SOPs. Responsibilities and Duties Delegated The following areas of sponsorship will be transferred to the CI or another organisation and will be operationally undertaken by the CI or another organisation unless it is otherwise agreed and documented. R&I will ensure that the following responsibilities are formally transferred to the CI or another organisation in an agreement or equivalent document: i. ethics and regulatory submissions; ii. statistical analysis; iii. data capture and data management; iv. data monitoring; v. investigational medicinal products or medical device manufacture and supply; vi. biological sample analysis.