Document Title: Project Management of Papworth Sponsored Studies

Document Title: Project Management of Papworth Sponsored Studies Document Number: SOP009 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: December 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 Papworth Staff who are involved in the management of Papworth Sponsored Research projects. It aims to provide clear guidance on managing study set up and study conduct to ensure compliance with the Trust s policies. Version 3.0 Review Date: December 2017 Page 1 of 9

1 Purpose and Content a. This document defines the project management responsibilities of the Sponsor or Chief investigator as part of the overall management of Papworth Sponsored Research Projects during site set up, study conduct and study closure and reporting. b. The document clarifies the requirements for project management to help ensure compliance with Good Clinical Practice guidelines (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 ). 2 Roles & Responsibilities a. This SOP should be read in conjunction with SOP 55: Roles and Responsibilities for the Conduct of Research Studies and Clinical Trials including CTIMPs (Clinical Trials of Investigational Medicine Products which defines the overall responsibilities of the Sponsor, The Chief Investigator and Principal investigators when conducting clinical research studies. b. Staff managing Papworth Sponsored Research Projects must comply with the requirements set out in section 4. c. The conduct of clinical research studies is the responsibility of the Sponsor, the Chief investigator and the Principal investigator at each participating site. The management duties that need to be completed as part of a clinical research study can be delegated but not the responsibility. This delegation needs to be clearly documented on the delegation of duties log. d. The management roles to be delegated by the Sponsor and Chief investigator will include the roles of overall Project manager, Data manager and Study Monitor. For smaller studies some of these roles may be combined into a single role profile or conducted by several trained staff. 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. Version 3.0 Review Date: December 2017 Page 2 of 9

4 Procedure 4.1 Prior to Trust Approval a. Once a potential Investigator wishes to proceed with a research idea a project team must be drawn together to discuss the study design, funding implications, potential funding sources, patient population, fit of the study with patient pathway, and implications on the service departments (see SOP013 Sponsor Files for Papworth Sponsored Studies). The frequency of project team meetings and their constitution must be agreed before the study starts. All project team meetings must be documented and the minutes filed in the Sponsor File. b. This team must include all parties required to ensure successful set-up of the study and is dependent on the type of study. This may include a sponsor representative (Senior R&D Manager or a Research Officer - RO), Statisticians, Health Economists, pharmacy and service department representatives. For a proposed Clinical Trial of an Investigational Medicinal Product (CTIMP) a pharmacy representative must be on the project team. c. Roles and responsibilities of the project team members should be agreed and clearly defined at this stage including, but not limited to: protocol design trial supply management completion of funding applications completion of regulatory and ethical application forms (as applicable to the type of study) completion of pragmatic risk assessment (SOP065: Risk-Adapted Approaches to the Management of Clinical Trials) CTIMPs only administrative duties including set-up and maintenance of the Sponsor File (see SOP013: Sponsor Files for Papworth Sponsored Studies) remit for patient & public involvement in the study communication plan data management including design of paper or electronic case report forms. The database and ongoing study data management periodic safety reporting and annual reports management of the study including site initiation (see SOP015: Site Recruitment and Initiation for Papworth Sponsored Studies) study co-ordination writing of final reports d. The Sponsor s representative (Senior R&D Manger or Research Officer) will provide advice in the set-up and management of the research study. The study must be appropriately funded and the research team must ensure that funding has been agreed prior to Trust Approval. The team must agree where to apply for appropriate funding (i.e. grant Version 3.0 Review Date: December 2017 Page 3 of 9

applications) and delegate duties for this application. The team must agree appropriate funding and delegation of duties. e. For studies that require grant funding: the team need to identify a suitable funding source a writing committee needs to be established with responsibility delegated to complete the various sections of the form and timescales set a lead must be identified to lead the application process if the study will be multi-centred, potential sites and co-applicants must be identified and be invited to the project team Patient & public involvement must be discussed and, if required, suitable representatives invited to assist with the work-up of the study. Researchers can contact appropriate PPI groups for support and advice e.g. the Eastern Clinical Research Network, INsPIRE (which is a local patient and public involvement group in health and social care). Sufficient time needs to be allowed prior to grant submission for the Trust to review costings and obtain the required Trust signatures. f. During the set-up of the study the following needs to be agreed. All decisions must be fully documented and filed in the Sponsor File: Requirement for outsourcing any of the study set-up including, but not limited to, pharmacy subcontractors to repackage and QP release study material, statistical and health economics support or use of a Clinical Trials Unit. The team must delegate who will be responsible for choosing the subcontractors. Setting-up of contracts with the subcontractors (see SOP066: Subcontracting of Research Activities) Requirement for a Trial Steering Committee and /or a Data Monitoring Committee (DMC). Agreement on the constitution, remit and frequency of meetings must be agreed at the start of the study, and this decision needs to be formally agreed by the Sponsor. All CTIMPs and external grant funded studies should have a Trial Steering Committee. The requirement for having a Data Monitoring Committee needs to be agreed on a study by study basis. Trials involving; subjects with life-threatening illnesses, vulnerable populations, significant risk of harm, or unknown or uncertain risks will usually require a DMC. They are most valuable in trials with long-term or survival-based outcome measures, which are more common in randomised controlled trials (particularly in areas like cancer, cardiology, etc) and less common in phase I or phase II trials. Frequency of checking for updates to the Summary of Product Characteristics / Investigator Brochure (CTIMPS only) and how changes to the SPC/IB will be notified to the wider project team. The frequency needs to be in relation to the risk profile of the drug and study. For example a licensed drug used within indication may require checks every 6 12 months, whereas an unlicensed drug or a drug being used outside of its indication may need to be checked every 12 weeks. Study timelines including recruitment targets Version 3.0 Review Date: December 2017 Page 4 of 9

Frequency and type of study monitoring. For example, 10% of all data monitored on-site; or central monitoring; or 100% baseline / inclusion data to be monitored (see SOP016 Monitoring Papworth Sponsored Studies) Training requirements for study personnel. If training is required it should be documented in the individuals training record following completion according to Training Record SOP (see SOP002: Training Records) Ensure the delegation log is completed, as appropriate (see SOP030 Roles and Responsibilities/Delegation Log ). g. Research Governance In addition to the above, the project team must complete the following activities: Research Governance / Trust Approval at each participating site Ensuring that for CTIMPs the protocol is signed by the Principal Investigator Site Initiation (following SOP015: Site Recruitment and Initiation for Papworth Sponsored Studies) Production of an Investigator Site File (following SOP010: Investigator File). In the case of a single centre Papworth sponsored study the Sponsor File can also act as the Investigator site file. Ensure the Regulatory Green Light process is followed in accordance with SOP034: Trust Approval and Research Governance. h. Data Management During study set up, the case report forms (SOP054: Case Report Form) and database (SOP057: Database Construction) will be designed and a study statistician will be involved. A study specific Data Management Plan will be documented in the Sponsor File and/or Protocol. The Data management plan should include: Details of the personnel involved Timelines Database Specification including Hardware and Software locations Database Structure Coding Dictionaries Data entry processes Details of associated SOPs for Data Entry, Data queries, Data cleaning and Database Lockdown The CRFs should be piloted prior to the study starting Version 3.0 Review Date: December 2017 Page 5 of 9

4.2 Study Conduct Following Trust Approval the project team will carry out the following activities (see SOP069: Emergency Un-blinding & Code-breaking of Clinical Trials and SOP018 Randomisation of Papworth Sponsored Clinical Trials): Review recruitment, withdrawals and follow-up at pre-agreed intervals which must be at least every 6 months Receive SAE and SUSARS reports, as per SOP012: Adverse Event Reporting, and report them as per the required timelines Hold Project team meeting, at the frequency agreed during study set-up, to check study status and address performance/clinical issues Arrange Trial Steering Group and Data Monitoring & Safety Committee meetings at the pre agreed time intervals. Circulate agendas prior to the meeting and summary notes/minutes after the meeting Update project team members on changes to the study design or timelines Review the Investigator Brochure/ Summary Product Characteristics according to the timescales agreed before the study started. Ensure that if there are changes to the IB/SPC these are reviewed against the current protocol and patient information sheet and changes made if required. These decisions must be formally documented. Ensure that the REC and Competent Authority/MHRA is informed when an amendment to the protocol or study documentation is made, and that approval/authorisation is received before the changes are implemented (unless there is an urgent safety issue). (See SOP037 Amendments to Research Documents of Papworth Sponsored Studies post Trust Approval). Ensure all sub-contractors e.g. pharmacy subcontractors are provided with updates to the protocol and study documentation (see SOP066 Subcontracting of Research Activities). Ensure that all mandatory reports are reported within agreed timescales. Complete accruals to the National Institute of Health Research (NIHR) database if adopted onto portfolio. Carry out staff training as required for both new and existing staff (see (need to ref training SOP but which one?) Ensure that staff have access to the necessary documentation Ensuring monitoring is completed according to the schedule agreed at the start of the study (following SOP016: Monitoring Papworth Sponsored Studies) Ensure that the data are managed in accordance with SOP053: Data Entry & Data Quality Control, SOP057 Database Construction, SOP058 Data Validation, SOP059 Closing Down a Database including Lock & Unlock Procedures The agendas for the Trial Steering Group and Data Monitoring & Safety Committee meetings must be agreed with the meeting Chair and circulated with the minutes of the previous meeting at least 1 week before the meeting. Version 3.0 Review Date: December 2017 Page 6 of 9

4.3 Study closure, Data analysis, Final reporting and Publication After the completion of the last patient, last visit for the research study the project team is responsible for (in accordance with SOP021: Trial Closure and End of Trial Reporting; SOP017: Statistics Input in Clinical Trials & SOP059: Closing Down a Database including Lock & Unlock Procedures ): Ensure all outstanding monitoring and data queries are resolved at each site Undertake a close-out visit at each study site Liaise with Pharmacy, if applicable, regarding the destruction of the IMP and archiving of the code break envelopes Complete end of trial forms for ethics, regulatory authorities and funders following database lock. Carry out final checks of Sponsor File and governance files Data Analysis Arranging a meeting of Trial Steering Group to agree and finalise the publication and dissemination strategy, and produce an action plan. It is the CI responsibility to ensure that this is carried out, but the project manager will monitor progress and arrange further discussions as necessary Review a publications and presentation plan Publish the data within 12 months of the database lock. If a journal article is not possible then a report must be filed on clinicaltrials.gov. Arrange archive of study documentations as per SOP011: Archiving SOP 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 3.0 Review Date: December 2017 Page 7 of 9

Further Document Information Approved by: Managment/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 Key related documents: Research and Development Directorate 5 th January 2015 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 Research and Development Standard Operating Procedures entitled: SOP002: Training Records SOP010: Investigator File SOP011: Archiving SOP SOP012: Adverse Event Reporting SOP013: Sponsor Files for Papworth Sponsored Studies SOP015: Site Recruitment and Initiation for Papworth Sponsored Studies SOP016: Monitoring Papworth Sponsored Studies SOP017: Statistical Input in Clinical Trials SOP019: Research Protocol Design for Papworth Sponsored Studies SOP021: Trial Closure and End of Trial Reporting SOP034: Trust Approval and Research Governance SOP053: Data Entry & Data Quality Control SOP054: Case Report Form SOP055: Roles and Responsibilities for the Conduct of Research Studies and Clinical Trials including CTIMPs (Clinical Trials of Investigational Medicine Products) SOP057: Database Construction SOP058: Data Validation SOP059: Closing Down a Database including Lock & Unlock Procedure SOP065: Risk-Adapted Approaches to the Management of Clinical Trials SOP066: Subcontracting of Research Activities 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 Version 3.0 Review Date: December 2017 Page 8 of 9

Yes/No NO NO NO NO NO NO NO Positive/Negative Review date: December 2017 Version Control Version Date effective Valid to Approved by Date of approval 1.0 2.0 3.0 2 nd February 2015 December 2017 RDD 9 th January 2015 4.0 Version 3.0 Review Date: December 2017 Page 9 of 9