STANDARD OPERATING PROCEDURE

Transcription

1 STANDARD OPERATING PROCEDURE Title Reference Number Maintaining Study Files SOP-RES-014 Version Number 2 Issue Date 08 th Dec 2015 Effective Date 22 nd January 2016 Review Date 22 nd January 2018 Author(s) Reviewer(s) Teresa O Leary, Head of Regulatory Compliance (Interim) Melanie Boulter, QA Auditor Authorisation (Original signatures are retained by Research & Innovation) Dr Brian Thomson Director of Research & Innovation Dr Stephen Fowlie Medical Director 24 th Nov th Dec 2015 USERS OF THIS STANDARD OPERATING PROCEDURE MUST REFER TO TO ENSURE THE MOST CURRENT VERSION IS BEING USED

2 Page 2 of 9 1. Document History Version Number Issue Date Reason for Change 1 30 th May 2014 Original SOP. Replaces SOP-2 and SOP th Dec 2015 Change of process for maintaining documentation for hosted studies.

3 Page 3 of 9 2. Introduction Essential documents relating to a study should be established at the beginning of the study, both at the investigator/institution site and at the sponsor's office (or contracted third party provider), and will be filed in such a manner as to allow reporting, interpretation and verification of the conduct of the study. The documents will also enable the sponsor, investigator and other persons involved in running the study to manage the study successfully. Essential documents provide the source documents from which the study can be audited and by which adherence to the principles of Good Clinical Practice (GCP) can be demonstrated. 3. Purpose and Scope This standard operating procedure (SOP) should be followed when setting up, initiating, running or providing services for a research study where Nottingham University Hospital NHS Trust (NUH) is the sponsor and applies to all NUH staff. This SOP sets out the procedure for setting up and management of the trial master file (TMF) and investigator site file (ISF) carried out at NUH and which need to meet the requirements of the Research Governance Framework for Health and Social Care (RGF). This SOP outlines both the essential documents which should be included in the TMF and ISF and how the TMF and ISF should be managed, stored and archived. For studies not sponsored by NUH, then the relevant sponsor SOPs will be followed and/or as outlined in the contractual agreement or study specific procedures for set-up of the sponsor s study files. All NUH governance documentation will be filed according to section Responsibilities Chief Investigator (CI)/Principal Investigator (PI) Overall responsibility for the maintenance of the ISF at the participating site. Sponsor (fulfilled by the Research and Innovation (R&I) department on behalf of NUH as sponsor) A designated person, normally the Research Project Manager (RPM), should take responsibility for the maintenance of the TMF and quality control (QC) checks. It also applies to any other individual(s) given the responsibility for setting up and maintaining a

4 Page 4 of 9 TMF. This can include researchers and third party provider working on behalf of the sponsor. 5. Definitions CI CMD CRF CSR CTIMP Documas GCP ICH IMP ISF MHRA NUH PI PSF QC R&I RGF RPM SOP TMF Chief Investigator Clinical Investigation of Medical Device Case Report Forms Clinical Study Report 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 Good Clinical Practice International Conference on Harmonisation Investigational Medicinal Product Investigator Site File Medicines and Healthcare products Regulatory Agency Nottingham University Hospital NHS Trust Principal Investigator Pharmacy Site File Quality Control Research & Innovation Research Governance Framework for Health and Social Care: Second Edition, 2005 Research Project Manager Standard Operating Procedure Trial Master File

5 Page 5 of 9 6. Procedure 6.1 Set-up and Maintenance of the Study Files Some studies may only require an ISF. Examples of such studies include the following: i. Study administering questionnaires/interviews for quantitative analysis, or using mixed quantitative/qualitative methodology; ii. Study involving qualitative methods only; iii. Study limited to working with human tissue samples (or other human biological samples) and / or data; iv. Study limited to working with data (specific project only); v. Research tissue bank; vi. Research database. Studies requiring a TMF include the following: i. CTIMP; ii. Clinical investigation or other study of a medical device (CMD); iii. Clinical study involving both an investigational medicinal product (IMP) and a medical device; iv. Other clinical study to examine a novel intervention or randomised clinical study to compare interventions in clinical practice; v. Basic science study involving procedures with human participants Investigator Site File including the Pharmacy Site File The investigator must ensure an ISF is established prior to the start of a study at their site. The investigator is responsible for setting up, maintaining, storing and archiving the ISF. This duty may be delegated to another appropriately qualified member of the local study team and recorded in Delegation Log (TAFR01202). The investigator or delegated individual sets up an ISF at the time the research is registered with the Research & Innovation (R&I) department. The ISF will be set up using the following ISF Index according to the type of study: TAFR01403 (CTIMPs), TAFR01406 (non CMDs), TAFR0140 (CMDs), PSF Index (TAFR01404)

6 Page 6 of 9 All files should contain numbered sections with file dividers as set out in the ISF Index and PSF Index. If some sections are empty because the corresponding section is used in a file held by another department at the site, e.g. Pharmacy, a cross-referencing Note to File (TAFR01405) must be inserted. The investigator should file documents promptly and file superseded documents in the appropriate section of the ISF, marked as superseded. The investigator should ensure all essential documents are filed in reverse date order unless specified otherwise. The investigator or delegated individual should carry out regular checks to ensure the contents are up to date and maintain a record of these checks. The ISF will be held in a secure location with access restricted to the local study team, R&I and designated representatives of the sponsor. Access will also be granted to auditors and monitors appointed by the sponsor and regulatory inspectors. The investigator should arrange for appropriate archiving of the ISF according to the requirements of the sponsor and appropriate regulatory authorities (refer to SOP-RES-028 Archiving and Destruction of Records) Trial Master File The sponsor is responsible for the set-up and maintenance of the TMF; however this duty may be delegated (as per an agreement) to the CI or a third party provider. The TMF contains all the essential documents (in accordance with International Conference on Harmonisation (ICH) GCP) relating to the study. The documents listed in section 8 of ICH GCP guidelines are considered to be the bare minimum essential documents and not a definitive list. These are documents that are generated before the study commences, during the study and after the study has finished. The sponsor or delegated individual must prepare the TMF, with the required contents page and numbered sections with dividers, before initiation of the site. A TMF must be produced for all studies sponsored by NUH, which require regulatory authorisation from the United Kingdom Competent Authority. The TMF, which can consist of a single file or a series of files, should be set up early in the development of a study and should be fully up to date by the time the study opens to recruitment. The TMF will be set up using the following TMF Index: TAFR01402 (CTIMPs), TAFR01408 (CMDs) The TMF should be kept up to date at all times. Superseded documents should be retained in the TMF (marked as superseded) thus providing an audit trail.

7 Page 7 of 9 If a document is physically too large to fit in the TMF binder (e.g. Case Report Form (CRF) binders) a Note to File will be added to the appropriate section to refer to the actual physical location of the document. Other documents which may be large in size (e.g. Clinical Study Report (CSR) and Appendices) should be printed where possible but may be stored on an electronic media storage device which should have integrity to be readable for the duration of the archive retention period. The TMF Document Log (TAFR01401) must be completed to record all documents contained within the TMF and in which sections these documents are held. The TMF will be held in a secure location (e.g. in a locked cupboard and in a room with swipe-card access), with access restricted to members of the study team and R&I department and designated representatives of the sponsor. Access will also be granted to auditors and monitors appointed by the sponsor and regulatory inspectors. Storage should both protect the TMF documents from possible damage and maintain confidentiality. However the TMF must be easily accessed by all personnel involved in the running of the study in order to allow access to information on the conduct of the study and to enable regular filing. On completion of the study, ensure that any correspondence detailing key decisions made or sponsor approvals etc. are maintained in the TMF, non-essential documents (e.g. general correspondence) should be removed and the TMF archived according to the protocol requirements (refer to SOP-RES-028 Archiving and Destruction of Records) Maintenance of Study Files During the Conduct of the Study All documents required to be held in the TMF must be hard copies and no documents can be held as electronic copies. Any electronic copies of documents held in the NUH shared drive or on Documas are working copies only and do not form part of the NUH TMF. The Research Project Manager (RPM) will ensure a QC check of the TMF for NUH sponsored CTIMPs is performed every six months to ensure that all study related documents are present, complete and readily available. This QC will be documented using the TMF Checklist (TAFR02806) and retained in the TMF. As part of the six monthly TMF review, all reported SAEs and SAE logs are reconciled to ensure safety reporting is up to date. For studies managed by a CTU, the R&I RPM will request the CTU to confirm that the Sponsor master SAE log is up to date with CTU SAE Log. The SAE reconciliation will be documented using the TMF Checklist (TAFR02806) and retained in the TMF. The ISF will be reviewed by the monitor on a regular basis in accordance with the relevant study Monitoring Plan to ensure that the study documentation maintained at the Investigational Site(s) is complete and contains all the relevant study documents. Any

8 Page 8 of 9 discrepancies will be highlighted to the study site personnel and documented in the monitoring reports (refer to SOP-RES-013 Monitoring). For file finalisation procedures refer to SOP-RES-026 Site Close Out.

9 Page 9 of NUH Hosted Studies For NUH hosted studies, research documentation (including HRA Approval/NHS permission, Statement of Activities, Feasibility etc.) must be scanned, uploaded to the R&I dedicated network folder. This will be the primary source for this information. Contract agreements containing wet signatures will be stored with Contracts Management Team. Scanned copies will be uploaded to the R&I dedicated network folder. Grant applications will be uploaded to the R&I dedicated network folder. This will be the primary source for this information. However, the ISF (Site Investigator file) will be the legal study documentation and managed according to Sponsor or study specific SOPs and retained accordingly. 2. References and Associated Documents Guidelines for Essential Documents for the Conduct of a Clinical Trial (ICH E6 Section 8). Research Governance Framework for Health and Social Care: Second Edition, 2005 Eudralex Volume 10 Clinical Trial Guidelines (chapter V Recommendation on the content of the trial master file and archiving) TAFR01202 TAFR01401 TAFR01402 TAFR01403 TAFR01404 TAFR01405 TAFR01407 TAFR01408 TAFR02806 SOP-RES-013 SOP-RES-026 SOP-RES-028 Delegation Log Trial Master File Document Log Trial Master File Index Investigator Site File Index Pharmacy Site File Index Note to File Investigator Site File Index (CMD) Trial Master File Index (CMD) Trial Master File Checklist Monitoring Site Close Out Archiving and Destruction of Records