Clinical Trial Delegation of Sponsorship Responsibilities to Chief This Agreement dated DD/MM/YYYY (the Effective Date ) is between Nottingham University Hospitals NHS Trust, Derby Road, Nottingham, NG7 2UH, UK(hereinafter referred to as the Sponsor ) AND The Nottingham Clinical Trials Unit, University of Nottingham (hereinafter referred to as the NCTU ) AND CI s Name, of Department, Address, (hereinafter referred to as the Chief ) WHEREAS for the conduct of the Clinical Trial entitled Insert Study Title ( the Clinical Trial ) NUH R&D Ref number: EudraCT number: (A) The Sponsor has agreed to take the responsibilities of Sponsor as defined by the Medicines for Human Use (Clinical Trials) Regulations 2004. (B) The Sponsor delegates responsibility for the management of the Clinical Trial to NCTU. (C) Chief has sufficient knowledge and experience to conduct this Clinical Trial. (D) The purpose of the Agreement is to provide for the proper management and governance of the Clinical Trial and to set out the respective roles and responsibilities that the Sponsor wishes to delegate to the Chief and/or subcontractors. 1. The Agreement shall commence on the Effective Date and shall remain in force until the trial end date. 2. The Chief and the NCTU shall undertake the responsibilities delegated by the Sponsor as set out below. 3. Where the Chief wishes to delegate responsibilities to another member of the Trial team, that individual must receive sufficient support and training to fulfil that role and all delegated duties must be detailed within the Trial Master File. Page 1 of 10
1 Sponsorship Undertake role of Sponsor as defined by the Medicines for Human Use (Clinical Trials) Regulations 2004, as amended. Responsibility for the liability and indemnity for the trial as defined under UK regulations. Appoint an individual to represent the sponsor s interests for the duration of the trial on the Trial Steering Committee 2 Trial Documentation ( inc Trial Master File (TMF), protocol, CRFs, PIS) Design the research protocol describing the objectives, design, methodology, statistical considerations and organisation of the trial Keep a TMF for the clinical trial containing the essential documents relating to the clinical trial Ensure that the TMF (and other appropriate trial files) is readily available at all reasonable times for inspection by the licensing authority or any person appointed by the Sponsor to audit the arrangements for the trial Prepare documentation to assist with the organisation, management and conduct of the trial. This documentation includes but is not limited to, participant information sheets, consent forms, case report forms, participant diaries, SOPs etc. Keep a TMF for the clinical trial containing the essential documents relating to the clinical trial Verify that the TMF contains all essential documents ( via a Trial Initiation Visit) prior to Trial commencement Ensure that the TMF (and other appropriate trial files) is readily available at all reasonable times for inspection by the licensing authority or any person appointed by the Sponsor to audit the arrangements for the trial 3 Permissions and notifications Ensure amendments to the CTA have been approved by (a) REC; and (b) MHRA Prior to implementation Application for the main Research Ethics Committee (REC) opinion. Request for authorisation to conduct a clinical trial made to the licensing authority ( MHRA.). Notify MHRA and the Sponsor of amendments to the CTA which includes an amendment to (a) The terms of the request for authorisation of the clinical trial; or (b) The particulars or documents that accompanied that request Application for the main Research Ethics Committee (REC) opinion. Request for authorisation to conduct a clinical trial made to the licensing authority (MHRA.). Notify MHRA and the Sponsor of amendments to the CTA which includes an amendment to (a) The terms of the request for authorisation of the clinical trial; or (b) The particulars or documents that accompanied that request Page 2 of 10
4 Trial Management Notify the REC and the Sponsor of amendments to the favourable opinion which includes an amendment to (a) The terms of the application for REC opinion; or (b) The particulars or documents that accompanied that application Notify MHRA, REC and the Sponsor that the trial has ended within 90 days of the conclusion of the trial Notify MHRA, REC and Sponsor within 15 days if the trial is terminated (a) Before the date for the conclusion of the trial specified in the protocol, or (b) Before the event specified in the protocol as the event which indicates the end of the trial has occurred.. Notify MHRA and Sponsor in writing of any serious breach of (a) the conditions and principles of GCP in connection with the trial (b) the protocol relating to the trial Immediately after becoming aware of that breach Provide the REC and the Sponsor with an annual progress report Ensure Site Registration process as described in the Protocol is complete before Trial commences at each Site. Notify the REC and the Sponsor of amendments to the favourable opinion which includes an amendment to (a) The terms of the application for REC opinion; or (b) The particulars or documents that accompanied that application Notify MHRA, REC and the Sponsor that the trial has ended within 90 days of the conclusion of the trial Notify MHRA, REC and Sponsor within 15 days if the trial is terminated (c) Before the date for the conclusion of the trial specified in the protocol, or (d) Before the event specified in the protocol as the event which indicates the end of the trial has occurred. Notify MHRA and Sponsor in writing of any serious breach of (a) the conditions and principles of GCP in connection with the trial (b) the protocol relating to the trial within 7 days of becoming aware of that breach Provide the REC and the Sponsor with an annual progress report Ensure Site Registration process as described in the Protocol is complete before Trial commences at each Site. Appoint and coordinate a trial management group (TMG) to consider day-to-day management issues and the overall progress of the trial Convene a trial steering committee to provide oversight of the trial. Convene an independent data monitoring committee (IDMC) to receive and review the progress and accruing data of the trial and provide advice on the conduct of the trial to TSC. 5 Contracts Page 3 of 10
Use the UKCRC mnca agreement and supporting documents as the suite of documents forming the agreements between NUH and collaborating NHS sites Ensuring that appropriate written agreements are in place between the Sponsor and any organizations carrying out duties on a subcontractual basis (including IMP supply agreements) 6 Conduct of the Trial Review Sponsor registration form, finalised protocol and participant information prior to REC submission 7 IT/Data Provide input into the negotiation of the contracts Ensure the conduct of Trial is in accordance with GCP and applicable Regulations Verify that The Trial Master File has all essential documents in place prior to Trial commencement Ensure the conduct of trial is in accordance with (a) the protocol (b) the terms of (i) the CTA (ii) REC approval Receive, read and follow all relevant central SOPs. Prepare standard operating procedures (SOPs) identified as necessary to manage the trial Ensure all researchers involved and participating sites and staff are aware of, trained in and complying with trial specific SOPs, via trial initiation meeting if appropriate Inform the participating site and the site principal investigator of the name and telephone number of the trial manager and the sponsor s representative. Implement adequate business continuity / disaster recovery plans to ensure recovery and restoration of critical trial functions following unforeseen disasters or extended disruption Ensuring regulatory compliant randomisation and/or registration into trials Ensure the conduct of Trial is in accordance with GCP and applicable Regulations Verify that The Trial Master File has all essential documents in place prior to Trial commencement Ensure the conduct of trial is in accordance with (a) the protocol (b) the terms of (i) the CTA (ii) REC approval Maintain central SOPs and make them available to CI Review and approve relevant Trial SOPs Ensure all researchers involved and participating sites and staff are aware of, trained in and complying with trial specific SOPs, via trial initiation meeting if appropriate Inform the participating site and the site principal investigator of the name and telephone number of the trial manager and the sponsor s representative. Implement adequate business continuity / disaster recovery plans to ensure recovery and restoration of critical trial functions following unforeseen disasters or extended disruption Ensure IT systems and processes are set up to ensure data integrity and archiving to adequate regulatory requirements including but not limited to database set up and hosting and IT security Page 4 of 10
Take on the role of Data Custodian and Systems Manager 8 Pharmacovigilance Make appropriate urgent safety measures in order to protect the participants of a clinical trial against any immediate hazards to their health or safety Make appropriate urgent safety measures in order to protect the participants of a clinical trial against any immediate hazards to their health or safety Assessment of SAEs Ensure that the Principal s responsible for the conduct of a trial are informed of any SUSAR which occurs in relation to an IMP used in that trial Make appropriate urgent safety measures in order to protect the participants of a clinical trial against any immediate hazards to their health or safety Report Urgent Safety measures to Sponsor, MHRA and REC Keep detailed records of all adverse events which are reported by the investigators for that trial. Ensure that SUSARs are (a) recorded; and (b) reported as soon as possible (i) the licensing (ii) authority, the relevant ethics committee, (iii) the Sponsor and in any event not later than 7 days (fatal or life threatening) or 15 days (nonfatal or life threatening) after the first awareness of the reaction Ensure that within 8 days of a report any additional information is sent to the licensing authority and the relevant ethics committee As soon as practicable after the end of the reporting year provide the licensing authority, the relevant ethics committee and Sponsor with (a) a list of all SUSARs which have occurred during that year, including those reactions relating to any IMP used as a placebo or as a reference in those trials a report on the safety of the participants of those trials a report on the safety of the participants of those trials As soon as practical after the end of the reporting year provide Principal s at each of the sites a line listing of all suspected serious adverse reactions which have occurred during that year Page 5 of 10
9 Monitoring 10 Archiving 11 Quality Assurance 12 Reporting and Finance Carry out central and site monitoring. Ensure that all documents contained, or have been contained, in the Sponsor TMF are retained for at least 5 years after the conclusion of the trial Appoint named individuals to be responsible for archiving the documents which are or have been contained in the TMF and, with the exception of the licensing authority and any person appointed by the Sponsor to audit the arrangements for the trial, access to those documents shall be restricted to those appointed individuals Ensure secure restricted access (to delegated individuals) archiving space that meets regulatory requirements Implement and maintain quality assurance and quality control systems with written SOPs to ensure that the research is conducted and data generated, documented and reported in compliance with the protocol, GCP and applicable regulatory requirements Ensure reporting to relevant groups including but not limited to the funders as per their requirements. Ensure grant funds are administered in accordance with the terms of the award, properly recorded and reported, and that requests to funders for renewal or re-allocation are made promptly 13 Statistics analysis and publication Ensuring regulatory and GCP compliant statistical arrangement including but not limited to design, statistical analysis and appropriate documentation Responsibility for producing the trial publication Page 6 of 10
Holder of any intellectual property including power to delegate decision for data release. 14 Drug and its movement Ensuring confidentiality to a level dictated by regulatory requirement or imposed by sponsor and/or funder Ensuring publication is sent for review to appropriate parties including but not limited to any party to whom the Sponsor has any legal obligations to give notice of publication Ensuring confidentiality to a level dictated by regulatory requirement or imposed by sponsor and/or funder Ensuring regulatory and GCP compliant data management including but not limited to CRF movement, databases and data handling and following up data queries. Ensure the investigator s brochure/smpc (if available) is valid and updated at least once a year Provide site principal investigators with (or link to) updated investigator s brochure/ SmPC (if available) as necessary Ensuring a regulatory compliant IMP handling/custody including but not limited to adequate QP release, documentation to ensure quality and certificate of analysis Central IMP accountability, ordering and distribution The undersigned confirm their acceptance of the terms of this Agreement For and on behalf of the Sponsor Name : Dr Maria Koufali Title : Asst. Director of Research & Innovation The Chief Name :.. Title :.. Signature Signature For and on behalf of the Nottingham Clinical Trials Unit Name : Title : Page 7 of 10
Signature Page 8 of 10
Schedule A Financial Arrangements The fees detailed below are the costs incurred by NUH as sponsor and each Party understands and accepts that payment of these fees is to be made in accordance with the following payment schedule: [DELETE AS APPROPRIATE] Non CTIMP Studies Payable upon receipt of R&D Approval Payable upon receipt of R&D Approval at Additional Sites Single Site (NUH Only) 1,500 Multiple Sites 1,000 500 per site The Payments detailed above are to be made in consideration of the following activities carried out by the Sponsor: Contract management including sub-contracts where necessary, financial oversight and funder reports Advice/Support (24/7, 365 days a year) Trial Registration Externally accessible server space for hosting web applications (websites, document repositories) Patient and Public Involvement (PPI) Advice and support [DELETE AS APPROPRIATE] CTIMP and Medical Device Studies Payable upon receipt of R&D Approval Annual Payments for each completed year Annual Payments for each completed year per additional site Single Site (NUH Only) 5,000 2,000 Multiple Sites 5,000 2,000 Annual payments shall be calculated on a pro rata basis where trial duration is less than 12 months or where a trial is subject to early termination. The payments detailed above are to be made in consideration of the following activities carried out by the Sponsor: Trial registration Externally accessible server space for hosting web applications (websites, document repositories) Patient and Public Involvement (PPI) including advice and support Monitoring including development of monitoring plans, site visits (and associated travel costs), attendance at data monitoring committees SOP compliance audits Contract management including sub-contracts where relevant, financial oversight and funder reports Site set-up site files, delegation logs etc Pharmacovigilance including safety reporting Contribution to Sponsor overheads including MHRA GCP inspection fees, environmental monitoring equipment Page 9 of 10
Archiving by a certified archivist in secure facilities for 15 years following study closure Support/advice with regulatory approvals including completion of forms (MHRA, REC) Training of study staff (e.g. GCP, pharmacovigilance, SOP s) Advice/Support (24/7, 365 days a year) Invoices to be submitted to: [INSERT DETAILS OF FUNDER WHERE NECESSARY] Payments to be made in accordance with the following Payee Name GBS Re Nottm Uni Hospital NHST Bank Account Number 12280086 Sort Code 08-33-00 IBAN GB69CITI08330012280086 BIC CITIGB2L Bank Name Citi Bank Bank Address Government Banking Service C/O Citi Bank, Citi Group Centre, 25 Canada Square, Canary Wharf, London E14 5LB Vat/Tax At current applicable rate VAT/Tax Details 654 4348 27 Address of Payee Nottingham University Hospitals NHS Trust, P.O. Box 5711, Finance Department, City Hospital Campus, Hucknall Road, Nottingham NG5 1PT Remittance Information /Company/R&D Ref No. Nottingham University Hospitals NHS Trust, P. O. Box 5711, Finance Department, City Hospital Campus, Hucknall Road, Nottingham NG5 1PT Or email: Cashiers@nuh.nhs.uk Page 10 of 10