Storage and Archiving of Research Documents SOP 6

Storage and Archiving of Research Documents SOP 6 SOP Title Storage and Archiving or Research Documents (Formerly Storage and Archiving Requirements ) SOP No. SOP 6 Author Consulted Departments Lead Manager Julia Farmery; Updated by Helen Ayre Lincolnshire Clinical Research Facility, Research and Development, Trust Consultants and Research staff. Prof. Tanweer Ahmed Director of LCRF and Head of Research and Development Sign and Print Name (Signature on file) Approved by : ULHT Clinical Records Review Committee and Clinical Effectiveness Steering Committee Date of publication / implementation 01/06/2017 Review date of SOP 01/06/2019 Version 3 Page 1 of 19

Version History Log This table should detail the version history for this document. It should detail the key changes when a version is amended. Version Date Implemented Details of key changes 1 10/03/2010-2 01/10/2014 This document has been significantly rewritten and it is recommended that all staff to whom this SOP is applicable familiarise themselves the content of this Version 2 Relevant SOP documentation updated Applies to section amended to detail relevant staff groups rather than research documents Clinical Trial Alert archiving sticker has been renamed as Research Records Retention sticker Removed all reference to photocopying relevant pages of notes and filing behind the blue divider as this is not required Checklists included in What should be archived? section. Destruction of essential documents section included Information on archiving of electronic research data included 3 01/06/2017 Clarification included regarding management of original prescription charts Updated with details of ReStore Document Page 2 of 19

Management (Replaced Magnum Services) 1. Purpose: The purpose of this Standard Operating Procedure is to describe the process for ensuring that all documentation pertaining to research conducted through the United Lincolnshire Hospitals NHS Trust, is retained and archived in line with applicable legislation and guidance. ICHGCP (Section 8.1) describes essential documents as those documents that individually and collectively permit the evaluation of the conduct of a trial and the quality of the data produced. These documents serve to demonstrate the compliance of the investigator, sponsor and monitor with the standards of good clinical practice and all applicable regulatory requirements. Essential documents must be retained (archived) for sufficient periods to allow for audit and inspection by regulatory authorities and should be readily available upon request. Source data (i.e. original records of clinical findings, observations and other activities in a clinical trial, necessary for the reconstruction and evaluation of the trial) form part of the essential documents and are likely to be contained within individual patient records, as well as within trial specific documents, such as case report forms (ICH GCP 1.51&1.52). It is therefore important to ensure that hospital records pertaining to a patient s involvement in clinical research are also retained for an appropriate period. For CTIMPs it is a legal requirement that the sponsor and the chief investigator ensure that the medical files of trial subjects are retained for at least 5 years after the conclusion of the trial (Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 - SI 2006:1928). Patient records will normally be retained for a minimum of 8 years from the beginning of the year after the last date of entry on the record, or 8 years after the patient s death. Although variable and longer retention periods apply in some circumstances (e.g. paediatrics, obstetrics, oncology); in all cases, usual retention requirements (outlined here: http://webservl1/applications/documents/views/get_file.aspx?id=30854) dictate that notes can be destroyed 8 years following the patient s death. Where patient records contain source data which will require retention for a period longer than 8 years following that patients final study visit (or possible death) the Research Nurse is responsible for affixing a Research Records Retention Alert sticker to the alert page of the patient notes and completing the Retention of Health Records section on the back inside cover of the patient notes (See Appendix 1). This is to ensure that notes are not inadvertently destroyed in accordance with usual retention procedures where research retention requirements are longer. In all cases the longest retention period relevant to a set of patient notes should be adhered to. Page 3 of 19

Box 1 Example A Patient A is one of the participants in a dermatology clinical trial which opened in January 2010 and has a 5 year recruitment period followed by 1 year follow up. The expected end date of the study is therefore End 2016. Patient A was recruited in June 2010, had 6 months of IMP treatment and her final study visit in June 2011. Assuming she has no further hospital attendances, her notes would be destroyed in 2020. However the study requires all notes to be retained until at least 2021 (5 years after the conclusion of the study). Patient A will therefore need a Research Records Retention Sticker adding to her notes. In the case of all research data, relevant elements of the Data Protection Act apply e.g. Personal data processed for any purpose or purposes shall not be kept for longer than is necessary for that purpose or those purposes (Data Protection Act 1998 (DPA) - Schedule 1, Part 1, Principle 5) For CTIMPS the storage of personal data is subject to applicable elements of the Medicines for Human Use (Clinical Trials) Regulations 2004, and subsequent amendments. (See Paragraph 6.4 for retention requirements and ULHT Clinical Records Retention and Disposal Policy for further information) 2. Applies to: This SOP is relevant to the following individuals: Chief Investigators (CIs) of ULH NHS Trust Sponsored (or Cosponsored) research projects Principal Investigators (PIs) of research projects hosted by the United Lincolnshire Hospitals NHS Trust (i.e. Sponsored by an external organisation) Staff working on both Trust Sponsored and/or Hosted research projects, particularly those who have been delegated the task of site file maintenance. ULHT Research & Development Staff CRN Study Support Service Staff working on behalf of ULHT ULHT Health Records Staff For studies Sponsored by the Trust this SOP should be referred to initially during the study design in order to ensure that retention and archiving requirements, and their associated costs, have been considered. For all hosted studies this SOP should be referred to during the NHS permission application process to ensure that costs of local archiving, where Page 4 of 19

applicable, have been considered. In all cases this SOP should also be referred to again by the investigator, or delegated individual (i.e. Research Nurse) as soon as practicable, following the end of a research study. 3. Relevant SOP Documentation: SOP 05 Privacy and Data Protection SOP 07 Trial Master File SOP 14 Study Planning and Feasibility SOP 16 - Sponsorship 4.Definitions: CI Chief Investigator CPMP - Committee for Proprietary Medicinal Products CRF Case Report Form CRN Clinical Research Network CRN EM Clinical Research Network East Midlands CTIMP Clinical Trial of an Investigational Medicinal Product GCP Good Clinical Practice. GCP is an international ethical and scientific quality standard for designing, conducting, recording and reporting trials that involve the participation of human subjects. ICH International Conference on Harmonisation ICH GCP - ICH HARMONISED TRIPARTITE GUIDELINE - GUIDELINE FOR GOOD CLINICAL PRACTICE E6(R1) IMP Investigational Medicinal ProductIRAS Integrated Research Application System ISF Investigator Site File PI Principal Investigator PIS Participant Information Sheet PIL Participant Information Leaflet PSF Pharmacy Site File R&D Research and Development department REC Research Ethics Committee TMF Trial Master File ULHT United Lincolnshire Hospitals NHS Trust 5.Policy: All current ULHT Health Records Policies are applicable in addition to this SOP. Current versions can be accessed at the following link: http://ulhintranet/corporate-policies Page 5 of 19

6. Procedure: 6.1 Determining the end of the study The definition of the end of the study should be defined in the study protocol and IRAS Forms. For Trust sponsored studies, the chief investigator is expected to liaise with R&D to confirm when the study has ended, and submit a notification of the end of study to the Sponsor and other regulatory authority(ies). For hosted studies a study is deemed to have ended following receipt of a close-out visit and report, and/or formal notification from the sponsor. 6.2 What happens if the study is extended? If a study is extended, the Chief Investigator is responsible for informing Principal Investigators and participating sites. Evidence must be stored within the Investigator Site File (and Sponsor Trial Master File, in the case of Trust sponsored studies) and ULHT R&D should be notified. The above process for determining the end of the study should then be followed. Where this will affect the retention period of clinical notes, all affected patient hospital notes must be obtained and the Research Records Retention sticker must be amended (or added, if applicable). 6.3. Who is responsible? The Research Governance Framework (Paragraph 3.6.3), which applies to all research studies states that it is the responsibility of the investigator to ensure that procedures are in place to ensure the integrity and confidentiality of data during processing and storage. They must also ensure that appropriate arrangements are in place to archive data when their research has finished, and to ensure that it is accessible so that all data and documentation associated with the study are available at the request of applicable authorities for auditing and/or inspection. It is a legal requirement for CTIMPs that the sponsor shall appoint named individuals within his organisation to be responsible for archiving the documents which are, or have been, contained in the trial master file and that access to those documents shall be restricted to those appointed individuals (whilst ensuring that all documents remain readily available for inspection by the licensing authority or sponsor). For ULHT Sponsored studies, this appointed Individual is the Named Archivist for the Trust (See Appendix 2). Any changes to ownership and/or location of archived essential documents should be documented by the sponsor and the new owner shall be responsible for data retention and archiving. For hosted studies it is common practice for responsibility for archiving of local documents to be delegated to the Principal Investigator and recorded within the Clinical Trial Agreement. Page 6 of 19

The ULHT Research & Development department has appointed a Named Archivist who is responsible for ensuring that all archiving requirements are met as defined in the UK Clinical Trials Regulations (and subsequent amendments) and this SOP. The Named Archivist will ensure that this is undertaken on behalf of investigators of both hosted and Trust sponsored studies. Following receipt of documents for archiving, ownership will transfer to the named archivist. However it is the responsibility of the Investigator to present documents to R&D in a state ready for archiving (See Section 6.6). Details of the current named archivist are available in Appendix 2 of this SOP. 6.4 Duration of archiving The sponsor is responsible for determining the duration of archiving required for study documents; and should consider: Whether the results of a trial will or may be included in a marketing authorisation application Applicable regulatory requirements at the time of archiving Any statements made in the protocol or submissions to regulatory authorities In the case of hosted studies, the Investigator should present confirmation from the Sponsor on the duration of archiving required, to the R&D along with the study documents which require archiving. In the case of Trust Sponsored studies, the duration of archiving will be agreed by R&D and the Chief Investigator at the start of the study but will also be reviewed and confirmed in writing on completion of the study. For multi-site Trust sponsored studies, consideration of site specific archiving requirements, as detailed by each participating R&D Department, is essential as these may differ from those outlined below. a. Trials which are not to be used in regulatory submissions Essential documents of the sponsor/trial organisers and investigators, from trials that are not to be used in regulatory submissions, should be retained for at least five years after completion of the trial. These documents should be retained for a longer period if required by the applicable regulatory requirement(s), the sponsor or the funder of the trial b. Trials to be included in regulatory submissions i. Sponsor's responsibilities The sponsor should retain all sponsor-specific essential documents in conformance with the applicable regulatory requirement(s) of the country / countries where the product is approved, and / or where the sponsor intends to apply for approval(s). Page 7 of 19

The sponsor-specific essential documents should be retained until at least two years after the last approval of a marketing application in the EU. These documents should be retained for a longer period if required by the applicable regulatory requirement(s) or if needed by the sponsor. In addition ICH GCP E6 guidelines will apply. ii. Investigator responsibilities Essential documents should be retained until at least two years after the last approval of a marketing application in the EU. These documents should be retained for a longer period however if required by the applicable regulatory requirement(s) or by agreement with the sponsor. It is the responsibility of the sponsor to inform the investigator/institution as to when these documents no longer need to be retained. All essential documents (TMF, CRF, other) should be archived in a secure room, with appropriate environmental controls (and adequate protection from fire, without water sprinkler systems, water, etc.) and accessed only by authorized personnel. United Lincolnshire Hospitals Trust use Restore Document Management for this purpose, which comply with these requirements. 6.5 What documents should be archived? Essential documents should be archived as soon as practicable after the completion of the study. (See notes on determining the end of the study). 6.5.1. For a CTIMP sponsored (or Co-Sponsored) by the ULH Trust the following documents should be archived: The Trial Master File (TMF) which should include: o Local Site Files o Case Report Forms (CRFs) o Pharmacy Site File o Sponsor File o R&D File o Any other documents that may be required to demonstrate a clear audit trail of a process performed in relation to a CTIMP o Any source data/documents which are not retained within a participants medical records 6.5.2 For a Non-CTIMP sponsored by the Trust the following documents should be archived: o Local Investigator Site Files o Case Report Forms (CRFs) o Sponsor File o R&D File o Any other documents that may be required to demonstrate a clear audit trail of a process performed Page 8 of 19

o Any source data/documents which are not retained within a participants medical records 6.5.3 For hosted CTIMPs where the sponsor has arranged archiving by the Trust, the following documents should be archived: o Local Investigator Site File o Trust held copies of Case Report Forms (CRFs) o Pharmacy Site File o R&D File o Any source data/documents which are not retained within a participants medical records o Any other documents that may be required to demonstrate a process performed in relation to a CTIMP, which have not been included in a participants medical file o Other support Department files (if applicable) 6.5.4 For hosted non-ctimps where the sponsor has arranged archiving by the Trust, the following documents should be archived: o Local Investigator Site File o Trust held copies of Case Report Forms (CRFs) o R&D File o Any other documents that may be required to demonstrate a clear audit trail of a process performed, which have not been included in a participants medical file o Any source data/documents which are not retained within a participants medical records 6.5.5 For hosted studies which are to be archived off-site by the Sponsor: The Sponsor s archiving procedures should be followed. The Sponsor should provide the PI with details of exactly what is to be archived off site. Consideration should be given to information provided within the Research Ethics Committee application, Participant Information Leaflets and informed consent forms regarding consent to transfer patient identifiable information outside of the Trust (i.e. it may not be appropriate to provide copies of signed consent forms, CRF s containing identifiable information etc.). As a minimum, the following should be retained and archived locally through the named archivist (copies taken where relevant): o R&D File o Consent Forms o Trust held copies of CRF s The sponsor should also provide details of how centrally archived documents can be recalled if required. This information must be passed to the Named Archivist along with the retained documentation. 6.6 Preparing Documents for Archiving A. Research Team Responsibilities All documents for hosted or Trust Sponsored studies which are to be archived by the Trust must be presented to the R&D unit in a state ready for archiving. Page 9 of 19

The Investigator or delegated individual should complete points 1-7 of the Trial Archiving Checklist (See Appendix 3) and forward this to the Research Governance Manager along with the study documents which require archiving. The site file should be organised in a suitable lever arch file, and be labelled with the name of the Investigator, Acronym/Short Study Title, REC reference, R&D Reference and Sponsor. All CRF s should be labelled with the patients Study ID, Acronym/Short Study Title, REC Reference & R&D Reference; or included in a file labelled with these details. All other essential documents should be filed in a lever arch file which should be labelled with the name of the Investigator, Acronym/Short Study Title, REC reference, R&D Reference and Sponsor. For CTIMPs the original prescription charts at the end of treatment are either placed in the patient s medical notes or stored in the PSF. If the original prescription is placed back into the medical notes a copy will be taken and stored in the PSF for reference and a Research Records Retention sticker should be placed in the patient notes. For CTIMPs only original copies of pharmacy prescriptions are to be included as part of the archived pharmacy file. Duplicate copies do not require archiving within the investigator site file essential documents and can be confidentially destroyed at the time of preparing documents for archiving. Source Data that forms part of current patient medical records (such as clinical observations, test results etc.) should remain within the patient s medical files and a note detailing the location of these source documents should be included in the archived documents. The Investigator is responsible for ensuring that medical notes of participants are appropriately labelled to prevent premature destruction. B.R&D Responsibilities Once the documents have been received in R&D, the Named Archivist will ensure that all trial related documentation is placed into a suitable archive box (boxes). Depending on the number of documents to be archived it is permissible to archive more than one study in one archive box. Prior to transferring the documents to secure storage for archiving, the Named Archivist will complete the R&D archiving log with details of the study(ies) archived, including the following information: Archive Box Number Short Title of Study R&D Reference REC Reference Page 10 of 19

Description of documents archived (i.e. site file, pharmacy file, CRF s for patients LCH001-LCH012) Name and Contact Details of Sponsor Name and Contact Details of Chief Investigator / Principal Investigator Date of transfer for archiving Location of long-term storage (i.e. ReStore Document Management Services, Goole; or other location as applicable) Retention period and expected destruction date The archive box will also be labelled with the box number corresponding to that listed on the R&D archiving log, brief summary of contents and details of the R&D account code for recharging of archive fees to the R&D department. The Named Archivist will transfer prepared archiving boxes to the ULHT Health Records Department, who will arrange for transfer to Restore Document Management within 24 hours. The named archivist will write to the Sponsor to inform them that study documents have been archived, providing details of the location and contact details of the named archivist. The R&D database (EDGE) will also be updated to reflect that study documents have been archived and the sponsor has been notified. 6.7 Retaining Medical Records On completion of a research study it is the responsibility of the Principal Investigator, or delegated individual to ensure that the medical notes of all research participants are labelled appropriately to ensure adequate retention. Investigators may wish to request the notes of all research participants to check that notes are labelled with the Research Records Retention sticker where required; that the destruction date is accurate, particularly where there have been extensions to the expected end date; and that copies of the PIS, completed consent form, copies of GP letters (where applicable) and a record of study visits are filed. 6.8 Storage and Archiving Conditions Storage whilst in use Whilst research projects are ongoing, study documents must be retained within a secure space, with restricted access. It is recognised practice to store documents in a locked cupboard, within a locked room. Documents should be maintained in a legible condition, with prompt retrieval possible. Responsibility for storage and maintenance of study documentation is the responsibility of the Investigator, or delegated individual. Long Term Storage / Archiving Page 11 of 19

Guidance states that adequate and suitable storage space for all essential records should be made available. The facilities should be secure, with appropriate environmental controls and adequate protection from fire, flood, pests and unauthorized access. They further state that this can be subcontracted out, yet the sponsor of the trial is ultimately responsible for all TMF documentation, so if we are not the sponsor, the sponsors may check we have adequate storage facilities in place (SAG, 2014) Lincolnshire Clinical Research Facility and Research and Development subcontract the archiving of Clinical Research records to a commercial off-site archiving facility (Restore Document Management) via the Trust health records team. Restore Document Management Services are regularly ISO 9001 inspected. They have built in 24hr monitors Swipe card access for all doors All notes and documents are stored above ground level, on raised shelves Temperature and Humidity controlled They have fire detection systems - which do not use water sprinklers Everything is bar-coded and stored accordingly for easy access and retrieval Research study documents archived under this SOP must be archived using these facilities, unless use of alternative facilities has been agreed and documented during the NHS permissions process. 6.9 Destruction of essential documents The sponsor should notify the investigator and essential documents owner in writing when their trial records can be destroyed and this information should be communicated to the Research & Development Department. The reasons for destruction of essential documents will be documented and signed by a person with appropriate authority (i.e. Director of R&D; or Head of R&D). This record, including a certificate of destruction provided by ReStore, will be retained permanently in line with the ULHT Clinical Records Retention and Disposal Policy, stored electronically within the R&D Drive at the following location:\\depts-b1\departments$\researchanddevelopment\shared\archiving The Named Archivist will notify the Sponsor in writing when destruction has been completed. 6.10 Archiving Research data on computers It is the responsibility of the CI/PI to notify the Named Archivist as soon as it is known that electronic study data will need to be archived. Electronic study data should be encrypted and copied onto a read-only media device for archiving with the study documents as described above. Study data held on computer servers should then be permanently deleted. This is the responsibility of the CI/PI, who should seek guidance from ULHT ICT department as required. Page 12 of 19

It is important to consider the most appropriate media for archiving electronic documentation. The selected medium should be unlikely to become obsolete during the planned period of storage, and should be transferred to a newer or more appropriate media format if necessary. References: Clinical Trials Toolkit. Archiving. Accessed on 14th August 2014 at: http://www.cttoolkit.ac.uk/routemap/archiving Data Protection Act 1998. (DPA) Schedule 1, Part 1, Principle 5. Accessed through the Department of Health website www.doh.gov.uk - Research involving the NHS : Retention of Records. EU Clinical Trial Directive (2001/20/EC) EU Commission Directive (2003/63/EC) ICH HARMONISED TRIPARTITE GUIDELINE - GUIDELINE FOR GOOD CLINICAL PRACTICE E6(R1) Available at: https://www.ich.org/fileadmin/public_web_site/ich_products/guidelines/efficacy/ E6/E6_R1_Guideline.pdf Scientific Archivists Group (SAG), 2014. Good Clinical Practice A guide to archiving. 2 nd Edition. [online] Available at: https://www.sagroup.org.uk/images/documents/gcparchiveguidejul2014.pdf [Accessed 1/06/2017] The UK Clinical Trial Regulations 2004 No. 1031, No. 2754, No. 2759, No. 1928, No. 2984, No. 941, No. 1164. The Research Governance Framework for health and Social Care, 2 nd Edition (2005). Department of Health. Statutory Instrument 2006 No. 1928 The Medicines for Human Use (Clinical trials) Amendment Regulations 2006 Adopted Information Information has been adapted for use from the following sources: York Foundation Trust R&D Unit SOP R&D/S11; with kind permission from Sarah Sheath (SOP Controller). Page 13 of 19

Imperial College London: Archiving Study Documents. Information adopted with kind permission of Professor Martin Wilkins. Many Thanks. This SOP will be reviewed every two years unless changes to legislation require otherwise. Current versions of all SOPs are located on the LCRF website users are responsible for ensuring that they are using the most up-to-date version Page 14 of 19

Appendix 1 PATIENT ALERTS * Do not remove from the Health Record * This section of the notes is for recording BLOOD GROUP, ALLERGIES, ANAESTHETIC REACTIONS, DISABILITY AWARENESS, INFECTION CONTROL, SAFEGUARDING AND CLINICAL TRIALS. It is important to complete this accurately, failure to do so may have serious consequences for the patient. Section 1 Blood Group Section 2 Infection Control Date Risk of Infection BBV, VRE, MRSA, CJD Alert Section 3 - Allergies Date Allergy Section 4 Anaesthetic Reactions Date Hazard Signature Section 5 Disability Awareness Wheelchair User Hard of Hearing Blind Partially Sighted Learning Difficulties Communication Difficulties Tick Section 6 - Safeguarding Safeguarding Children Adult Safeguarding Domestic Abuse Tick Section 7 Clinical Trials Affix: Clinical Trial Alert Sticker (If applicable) (Red) Affix: Research Records Retention Sticker (Green) Page 15 of 19

CLINICAL TRIALS (This is the blue divider section to be placed at the back of the patient notes). RESEARCH RECORDS RETENTION Name of Trial............... Retain for........ years after: End of Trial (expected)........... Date of destruction............. Authorise by Research Governance Manager Attach 24hr card if on a CTIMP trial CLINICAL TRIAL ALERT This patient is on a drug trial. Please see Clinical Trial section in back of folder for information. This may affect your treatment. Page 16 of 19

Appendix 2 Contact Details The current R&D Named Archivists can be contacted as below: Dr Tanweer Ahmed Head of R&D / Director of Lincolnshire Clinical Research Facility United Lincolnshire Hospitals NHS Trust Greetwell Road Lincoln LN2 5QY Tanweer.ahmed@ulh.nhs.uk Helen Ayre Research Manager Lincolnshire Clinical Research Facility United Lincolnshire Hospitals NHS Trust Greetwell Road Lincoln LN2 5QY Helen.Ayre@ulh.nhs.uk Trust Archiving Facilities Restore Document Management Britannia Way/Glews Hollow Goole DN14 6ES Page 17 of 19

Appendix 3 - Trial Archiving Checklist Involvement Task Checked By 1. Study closed to recruitment and follow up completed? PI/Nurse/Data Manager Involvement. 2. Close out e-mail from company received/close out visit completed. Please attach a copy. 3. Received details from Sponsor of [Insert or attach]: Name and Contact of Sponsor Address of Sponsor Duration of storage required by Sponsor. 4. Pharmacy confirmed ready to close down study (Only if CTIMP) 5. All equipment returned to Sponsor (as applicable)? 6. Patient Specimens (if applicable) sent to Sponsor (or destroyed)? 7. EDGE database updated incl.removal of identifiable data of screened patients? N.B. Do not change status to archived. 8. All documents (e.g. CRFs, ISFs, TMFs, IBs etc), sponsor details and duration of storage sent to Named Archivist 9. Pharmacy File obtained Date 10. R&D Application file obtained R&D Team Involvement (Named Archivist & SSS Coordinator) 11. Archived? Box Number: Duration of storage: Destruction year: EDGE status updated? Signed by: PI / Nurse (once points 1-7 complete) Date: Named Archivist (once points 8-10 complete) Date: Page 18 of 19

Appendix 4 Page 19 of 19