Research Study Close-down and Archiving Procedures

Transcription

1 Title: Research Study Close-down and Archiving Procedures Outcome Statement: To inform researchers of the process for closing down research studies, retaining and storing research materials in the Trust. Written By: Bonnie Teague, Research Manager Reviewed: Joanna Williams, Clinical Studies Officer In Consultation With: ICT Security and Governance Manager Approved By and Date: V1.0 Research Governance Committee, 26 th September 2013 V2.0 NSFT Research Committee, 25 th May 2017 References and EU ICH E2F, European Medicines Agency 2010 Bibliography: ICH Topic E 6 (R1): Guideline for Good Clinical Practice Department of Health: Research governance framework for health and social care: Second edition, 24 April 2005 Medicines for Human Use in Clinical Trial Regulations (2004) Associated Trust IG-61 Network Structure, Configuration and Security Policies and IG2-6 Storing Information Electronically Documents: R&D005 Conducting Clinical Trials of Investigational Medicinal Products R&D008 Trial Management: Trial Master Files and Site-Specific Files R&D009 Research Auditing and Monitoring Processes R&D016 Research Adverse Event and Safety Reporting Procedures Applicable To: Trust staff working on research studies taking place in NSFT. For Use By: Research Teams, Chief Investigators, Research and Development, Clinical Teams Reference Number: R&D013 Version: 2.0 Published Date: th September st June 2017 Review Date: 5 years Equality Assessment: Completed 19 th September Implementation To be implemented by the Research Office and detailed in Research training courses. Adherence to policy will be monitored on an annual basis using departmental database of archived studies. Page 1 of 14

2 Review and Amendment Log Version Number Reasons for Review Date Description of Change(s) 1.0 Regulations and guidance about 27th N/A research management state that each participating NHS Trust should have procedures and policies in place to support closedown of research and the archiving of research materials on site. September To update procedures for Study close-down and archiving. 25 th May Add electronic archiving procedures. 2. Standardise archiving period to 10 years for all studies. Page 2 of 14

3 1.0 Introduction In accordance with the Clinical Trial Regulations 2006 and the Research Governance Framework for Health and Social Care 2005, essential documents related to the conduct of a research study are required to be retained securely for a defined period of time after the completion of a trial. During the period of retention, research studies may be subject to auditing by sponsors or the Research and Development Office or Inspections by Regulatory Authorities. Each participating Trust in a research study requires a formal system in place for the long-term storage and security of research documentation. Clinical Trial Regulations and the Research Governance Framework also require processes and systems to be in place for the close-down or termination of research studies at an Institutional level. 2.0 Purpose The purpose of this Standard Operating Policy (SOP) is to describe the measures and actions to be followed by researchers working on research studies within the NSFT when: 1) Closing down or terminating a research study, 2) Arranging for long-term storage for research data (archiving) both paper and electronic archiving. This policy is relevant for studies being sponsored by the NSFT and for studies sponsored by external organisations. 3.0 Definitions and Abbreviations Case Report Forms (CRFs): A record of data collected for the specific purposes of clinical research, completed using source data. CRFs are used to collect data generated for a trial subject, in accordance with the protocol, during the course of their participation in a trial. They also ensure compliance with regulatory requirements. CRFs can be in paper, optical or electronic format, depending on the needs of the study protocol, but all should be dated and version controlled. Chief Investigator (CI): The lead researcher who has overall responsibility and oversight for the conduct of the research study across all sites, including maintaining study documentation. Clinical Trial of an Investigational Medicinal Product (CTIMP) A Clinical Trial of an Investigational Medicinal Product (CTIMP) is defined in the Medicines for Human Use (Clinical Trial) Regulations 2004 as any investigation in human subjects, other than a non interventional trial intended: To discover or verify the clinical, pharmacological or other pharmocodynamic effects of one or more medicinal products To identify one or more adverse effects of these medicinal products To study absorption, excretion or distribution of medicinal products with a view of ascertaining the safety or efficacy of such products. Since May 2004 when the Trial Regulations came into force, CTIMPs have been regulated by the Medicines and Healthcare Products Regulatory Agency (MHRA) who needs to give explicit authorisation for a CTIMP to be conducted in addition to the standard approvals required for clinical studies. This is termed Clinical Trial Authorisation or CTA. Essential Documents: Essential documents are those documents which individually or collectively permit the evaluation of the conduct of a trial and the quality of the data produced. (ICH GCP manual pg 21) and should be kept in a secure but accessible manner, they should be Page 3 of 14

4 legible, accurate and with a clear description as to it s purpose. Examples of essential documents include: Case report forms Delegation of Duties Log signed by all research staff and agreed by the Principal Investigator. Serious adverse events/reactions (SAEs/SARs) Suspected Unexpected Serious Adverse Events (SUSARs) Protocols Investigational Brochures Patient information leaflets Amendments to documents and protocols Communication Pharmacological documentation This list is not an exhaustible list of what could be regarded as essential. Further information can be found in Appendix 2. GCP: Good Clinical Practice. Good clinical practice is a set of internationally-recognised ethical and scientific quality requirements which must be observed for designing, conducting, recording and reporting clinical trials that involve the participation of human subjects. [Definition from EU Directive 2001/20/EC, article 1, clause 2] Compliance with this good practice provides assurance that the rights, safety and well-being of trial subjects are protected, and that the results of the clinical trials are credible and accurate. MHRA: Medicines and Healthcare Products Regulatory Authority. The MHRA's Good Clinical Practice (GCP) Inspectorate is part of the Inspection, Standards and Enforcement Division of the MHRA. The function of the GCP Inspectorate is to assess the compliance of organisations with UK and EU legislation relating to the conduct of clinical trials in investigational medicinal products. This is achieved through carrying out inspections of sponsor organisations that hold clinical trial authorisations (CTA) or organisations that provide services to clinical trial sponsors (host organisations). Principal Investigator (PI): The named researcher who has delegated responsibility for the conduct and oversight of the research study at each individual participating research site. Research Team Member: A research practitioner employed by the research team, Trust or research body to carry out specific allocated duties pertaining to the particular study. Investigator Site File (ISF): This file is held with the PI on each specific participating trial site. An Investigator Site File should offer a comprehensive, accurate and auditable story of the trial at the participating site. (ICH GCP manual pg 21) In some studies in the NSFT where localities and teams work on studies independently there may be a number of files that would be regarded as Site Specific Files. In such cases an individual should be nominated to be responsible for the maintenance of the file and all the relevant documentation available. Research Archive Custodians: Nominated Research department staff responsible for the secure archiving of electronic and paper research study data. Source Data: Source data are all information in original records and certified copies of original records of clinical findings, observations, or other activities in a clinical trial necessary for the reconstruction and evaluation of the clinical trial. Source data are contained in source documents Page 4 of 14

5 (original records or certified copies). Source documents are original documents and records where study data are first recorded e.g. hospital records, clinical and office charts, laboratory notes, memoranda, subjects' diaries or evaluation checklists and pharmacy dispensing records. Source documents are considered "Essential Documents" that allow evaluation of the clinical trial and ensure the quality of the data and serve to certify Sponsor and CI compliance with GCP and regulatory requirements. The process referred to as Source Data Verification (SDV) is an evaluation of the data recorded in the data collection tool against the source documents. Trial Master File (TMF): A master file kept by the study sponsor or CI. It contains all the essential documents and correspondence for the study. Whilst TMF guidelines are directed towards CTIMP trials, Non-CTIMP studies should also follow the standard outlined and is specified by the ICH GCP when it refers to a Trial Master File as being for all studies, not only clinical trials. (ICH GCP manual pg 21) 4.0 Duties and Responsibilities 4.1 Sponsor: The Institution with legal responsibility for the conduct of the research study across all participating sites. The sponsor is responsible for: Study set-up and full trial documentation set-up with study training arranged to local research teams. Establishing comprehensive monitoring and audit functions throughout the study by arrangement with local teams. Informing regulatory and other approving authorities of study close-down or early termination. Confirmation with local sites that the study has been archived in accordance with sponsor policy and/or study protocol. For Clinical trials of investigational medicinal products (CTIMPs) or medical devices, it is the legal responsibility of the sponsor (or delegated to Chief Investigator) to notify the regulatory authority (MHRA) and approving Research Ethics Committees within 15 days that the study has terminated early at each site. This notification should be stored within study documents prior to archiving. 4.2 Chief investigator (CI): The lead researcher with responsibility for the conduct of the clinical trial across all research sites, including but not limited to the following areas. Premature Termination or Suspension of Trial Responsible for ensuring trial subjects, institution sponsor and research approving bodies are promptly informed if trial ends prematurely or is suspended Final Report ensure that final report is provided to research approving bodies and sponsor The CI will be responsible for the integrity of the study protocol and publications resulting from the study. 4.3 Principal Investigator (PI); The lead researcher with delegated responsibility for the conduct of the clinical trial aligned with the responsibilities of the chief investigator (listed above) across the local site only. Duties will include: Page 5 of 14

6 Responsible for the set-up and conduct of the study at the local site and ensure that all trial documentation and appropriate training has been received and passed onto the study team. Inform Chief Investigator, Local Research Team and local Research Office about the close-down or early termination of the study. Nominate or delegate duties to a member of the local research team to undertake study shutdown and archiving processes as stated on the delegation log. 4.4 Local Research Team Clinical Studies Officer/Research Nurse/Research Assistant, if delegated by the PI and supervised appropriately, support the conduct of the research study at the local site, if recorded on the study delegation log: Duties could include: Arrange for local archiving of study documentation if duty is delegated for this role. 4.5 Trust Research and Development (R&D) office: The participating NHS organisation is required to have procedures in place for conducting the trial locally. These procedures include: Ensuring clarity of roles and responsibilities (e.g. contracts and agreement, delegation log) Appropriate knowledge of the trial and quality systems in all peripheral departments (e.g. laboratories, radiology, medical records); Ensure systems and facilities are fit for purpose (e.g. computer systems, equipment) Arrange for local study data to be archived on Trust premises in collaboration with study research teams. Assist local study teams to perform study shut-down procedures and undertake local close-down or study termination monitoring and audit visits. Manage process for electronic archiving of data in collaboration with ICT. Compliance with GCP guidance, Clinical Trial Regulations and any other relevant frameworks as assessed through local approval procedures and audit/monitoring of the study as required. Nomination of named Research Archive Custodian for the Organisation. Page 6 of 14

7 5.0 Main Policy Sections 5.1 Study Close-down The proposed end date of a research study is determined by the study protocol. The protocol should also state the circumstances or events which may determine an early termination date. These events may include Safety Concerns Poor Participant reaction/tolerance to study intervention Poor recruitment Sponsor s decision Investigator s decision For NSFT-sponsored studies, it is the duty of the Chief Investigator to inform the NSFT Research Office as soon as possible that the study has, or shortly will be, terminated. The Chief Investigator should also inform all Principal Investigators about the end of the study with a detailed written explanation of the termination or suspension For non-nsft sponsored studies, the Principal Investigator will be informed by the Chief Investigator or the sponsor about the study closure. It is the duty of the Principal Investigator to inform the NSFT Research Office about the end of the study so that monitoring and archiving processes can be completed For all studies, the Principal Investigator must submit a Study Close-down/Termination report to the NSFT Research Office (Appendix 1) If the trial is prematurely terminated or suspended for any reason, the Principal investigator, upon consultation with the Sponsor and Chief Investigator should promptly inform the trial subjects and assure appropriate therapy and follow-up for the subjects Archiving procedures should not be undertaken until study close-down procedures have been completed. In some cases, this may require the sponsor to conduct a final monitoring visit to reconcile study files prior to storage Once study close-down/termination procedures have been completed, it is the duty of the principal investigator to inform the Chief investigator that the study has closed/terminated at the local site. 5.2 Auditing and Monitoring Outcomes All studies in the NSFT may be subject to a final close-down audit at the end of the study. This will be performed by the Sponsor, Regulatory Authority and/or NSFT Research office upon notification of the close of the study. Studies should not be archived until acknowledgement has been received by NSFT Research Office If there are any significant findings or actions required as a result of final audits or any outstanding findings from previous audits conducted by the Research Office, sponsor or regulatory authority, it is expected that the study will not be archived until the identified issues have been resolved. Page 7 of 14

8 5.3 Duration of required Archiving NSFT-sponsored studies. The duration to store study materials should be clearly written within the original approval application forms and the study protocol. For studies sponsored by the NSFT, the following duration is required for archiving essential study materials: All studies - Observational and Interventional Studies. 10 years For studies not sponsored by the NSFT including all Clinical Trials of Investigational Medicinal Products, the storage duration for all research materials could range from 5-35 years as recorded by the protocol and sponsor policy. 5.4 Electronic Data Storage and Archiving Back-up archiving of study materials on secure NSFT servers is allowable, however, it is required that as many documents and spreadsheets as possible are printed out and filed with main documentation Where research data must be stored electronically, the data is required to be placed onto a secure transferable electronic format i.e. encrypted memory stick, and sent to Research and Development at the same time as the paper files to be archived. Alternatively, electronic files which are saved on the secure shared research drive can be archived directly The data will be stored on a secure NSFT server which can be accessed for auditing or safety purposes by nominated Research Archive Custodians only. The NSFT electronic research study archive adheres to Trust policies and standards for physical and environmental security for long-term storage, including server back-up and disaster recovery operations Study Databases For NSFT-sponsored studies, where studies hold research information on electronic databases, the designated database manager should undertake database lock-down procedures to ensure that access to the final dataset is restricted for final analysis, prior to study archiving. Digital preservation issues should be agreed prior to archiving to ensure that access is maintained as required throughout the archiving period. 5.5 Procedure for archiving studies (Paper-based) All research materials related to NSFT participants and studies must be archived within the Trust through Research and Development, following Research Archive Guidance, unless otherwise approved, as soon as go-ahead for archiving is confirmed by the Sponsor The location of the archived research study is held through a secure facility managed by Health Records in NSFT. The current location of the Research Archive is: S Block Hospital Road Bury St Edmunds, IP33 3NR. Page 8 of 14

9 5.5.3 Any participant identifiable information should be archived separately from anonymised/crf data by placing the information in either a separate archive box or a clearly marked sealed envelope If study team members have left the Trust before archiving, or do not have the capacity to archive, another member of the research team with delegated authority, may complete the archiving process, once study documents and the Archive request forms have been received in the office. 5.6 Accessing Archived Studies In the case of the study team or auditors requiring access to archived study material, the study team must put in a request in writing to R&D at least 7 days in advance of the date required, with a clear justification as to why access is required R&D will arrange for the box to be transferred back to the R&D office from Health Records, where it will be held securely until the study team can collect the box After the study team or auditors have completed their tasks, the boxes will be archived using the same steps as above. Page 9 of 14

10 Appendix 1: Research Project Close-down/Termination Report Template 1. Investigators Details NSFT RESEARCH PROJECT CLOSE-DOWN/TERMINATION REPORT Research & Development The Knowledge Centre Hellesdon Hospital Drayton High Road Norwich NR6 5BE Tel: Fax: Chief Investigator Principal Investigator Name: Address: Telephone: 2. Details of study Full title of study: Name of main REC: REC reference number: R&D Number: Date NSFT R&D approval received: 3. Commencement and termination dates What was the actual start date? What was the actual completion date? Was the completion date as scheduled? If no, state the reason why (For studies which have terminated earlier than expected, please give a full explanation on a separate document if required) Page 10 of 14

11 4. Recruitment of participants Number of participants recruited: Number of participants completing trial: Number of withdrawals due to: (a) lack of efficacy (b) adverse events (c) self-withdrawal (d) non-compliance (e) other Total number of withdrawals: Were there been any serious difficulties in recruiting participants? If Yes, give details: Proposed in original application: Actual number recruited: Proposed in original application: Actual number completed: Yes / No Have there been any protocol violations? Yes/No If Yes, give details and any remedial action taken: Have there been any Serious Adverse Events for the study? Yes/No If Yes, please give details of how many at each participating site: 5. Reports Self-audit report(s) submitted: Previous annual reports are available and archived with study files: (Annual reports include: Trust R&D, Ethics and, where applicable, funding bodies) Yes / No Yes / No Page 11 of 14

12 6. Other Please list any give any other information that you feel relevant (e.g. any difficulties incurred etc). Next Steps: Please send this signed report to: (scanned, electronic format) or Research and Development, The Knowledge Centre, Hellesdon Hospital, Drayton High Road, Norwich, NR6 5BE (hard copy, wet-ink format) Prepare your study for full close-down and archiving in the NSFT. Inform REC and other approving bodies of Study close-down retain reports in study files. Complete Final self-audit report for submission with this report Confirm that all site PIs have been informed of study termination/close-down. Inform NSFT R&D of any future publications arising from the study. Inform study funders of any future publications arising from the study (usually 28 days notice). Final Study Audit: Please indicate here if you wish for the Research Office to conduct a final close-down audit (if not performed recently). 7. Declaration I declare that all information in this final report is correct to the best of my knowledge. I have delegated the study shut-down and archiving duties to the following named member of the research team:.. [NAME OF RESEARCH TEAM MEMBER]. Signature of Principal Investigator: Print name: Date: NB The formal date of study close-down/termination at the NSFT will be the date stated by the Principal Investigator above. Page 12 of 14

13 Appendix 2: List of Research Documents to be archived after completion or termination of a research study. Non-Identifable or Participant Specific Documents Approved Protocol including amendments. Approved templates of Patient information sheets, letters of invitation and Consent forms. Clean templates of other participant information i.e. GP letters. Regulatory applications and approval documentation (including amendments). Sponsorship Acceptance Letter Ethics Committee composition/membership Delegation and Signature logs. CVs of Research Team Training Logs and relevant certificates of Research Team. Correspondence/newsletter/reports. Annual Reports and Safety reports. Financial and Contractual information plus Indemnity certificates. Investigator Brochure (plus revisions) Meeting Minutes and Agendas. Trial set-up, Audit and monitoring reports. Close-down and final reports (including End of Trial Notification). Details of data management and database systems including validation. Calibration Certificates (for equipment) Copies of Study-related reports and publications. Pharmacy-related Files (CTIMPs only): Instructions for handling and storing investigational medicinal products Sample of label for investigational products Shipping records for investigational products Decoding procedures for blinded studies Investigational Product Accountability Log Pharmacy Delegation Log Temperature logs Certificate of analysis of investigational products Patient specific or identifiable Documents [Kept separately] Case report forms. Appointment logs. Permission to contact forms. Signed consent forms. Data Queries and File Notes. Patient notes. Participant correspondence. Search list for identifying eligible patients. Subject Screening and recruitment logs Communication logs with participants. Completed SAE/R & SUSAR Logs and Forms. Treatment Allocation/Randomisation List and Information Clinical Study reports Page 13 of 14

14 Monitoring Statement Aspects of the policy to be monitored Timeline and reporting procedure s to regulatory authorities Monitoring method Changes to EU regulations and REC reporting to be monitored by R&D in accordance with published guidance. Individual/Team responsible for monitoring Research Manager (Research and Development) Frequency Annually to be reviewed, changes monitored constantly in response to national publications. Findings: Group/Comm ittee that will receive the findings/moni toring report Research Committee Action: Group/Committe e responsible for ensuring actions are completed Research Committee Page 14 of 14