Audit for Research Governance Purposes and Study Monitoring

Transcription

1 Audit for Research Governance Purposes and Study Monitoring The current version of all Hillingdon Hospital R&D Guidance Documents and Standard Operating Procedures are available from the R&D Intranet and Internet sites: Please ensure that you have the latest version. Version Number: 2.0 Effective Date: Review Date: Version Number Edited by Effective Date 1.0 JG/GB Document History 2.0 GB Reviewed Details of Changes First version Previously part of the SOP Audit and Inspection BACKGROUND A percentage of all research and development projects will be audited annually by the Research and Development staff. This is a local process to improve local standards, and the findings may be shared with others to improve practice. The definition of audit is A quality improvement process that seeks to improve patient care and outcomes through systematic review of care against explicit criteria and the implementation of change (This definition is endorsed by the National Institute for Clinical Excellence). This role is undertaken by the Trust s R&D staff. Study monitoring is the responsibility of the sponsor and should be undertaken on a regular basis by a person appointed by the sponsor. The ICH GCP guidelines define monitoring as A systematic and independent examination of trial related activities and documents to determine whether the evaluated trial related activities were conducted, and the data were recorded, analysed and accurately reported according to the protocol, sponsor s SOPs, GCP and the applicable regulatory requirement. The Trust does not consider it appropriate for local staff to be nominated to undertake study monitoring by the sponsor as this should be undertaken by 1

2 an independent person appointed by the sponsor. Only in cases where the Trust acts as sponsor will the R&D Office undertake this role. 2. PURPOSE Audit To assess compliance with research governance standards for studies being carried out within the Trust. Monitoring To assess the site s compliance with the protocol and other study documentation; to ensure that patient meet the inclusion and exclusion criteria, are recruited and consented as detailed in the protocol, that the source data is accurate and collected in a timely manner as per protocol. 3. PROCEDURE 3.1 Who? Audit The R&D Steering group will identify the audit program for the year. The R&D Manager will agree with the data manager or clinical trials co-ordinator the most appropriate person to undertake the audit. Monitoring Requirements for monitoring should be detailed in the protocol or clinical trial agreement. Consent forms should include consent from the patient to review the medical notes and research notes of individual patients. 3.2 When? Audit Audits can take place prior to, during and after the patient recruitment phase. A convenient time will be agreed with the Principal Investigator. Monitoring Study monitoring will be arranged between the Principal Investigator and the Monitor. The frequency may be detailed in the protocol. 3.3 How? Audit The Audit will include: 1. Location of storage of the research records and the completeness of the site master file 2. The completeness of the Participant Research records 3. The documents held and information documented relating to the study in the Patients Medical records 4. The completeness of the Pharmacy records and product storage 2

3 Monitoring The monitoring will cover the site master file, patients research files, hospital records, pharmacy files, and any other areas that are involved in the research. 4. OTHER RELATED PROCEDURES Archiving and Destroying Documents Study Files and Filing Case Record Form (CRF) Completion 5. REFERENCES AND FURTHER READING ICH Harmonised Tripartite Guideline for Good Clinical Practice (1996). The Medicines for Human Use (Clinical Trials) Regulations 2004 Statutory Instrument 2006/1031, implemented 1 st May 2004 as amended. 6. APPENDICES Research Study Documentation 3

4 Appendix 1 RESEARCH STUDY DOCUMENTATION The following details the documents that should be kept in the trust are as follows: The Trial master file Electronic site file Pharmacy file R&D Office file Other departments research documentation files TRIAL MASTER FILE Held by the Principal investigator The Trial Master File is the main research file in paper copy held in the Trust. It contains all essential documents (in accordance with ICH-GCP) relating to the clinical trial. These are documents are generated before the trial commences, during the trial (amendment documents and supporting documents, file notes and other logged conversations / correspondence) and after the trial has finished. It is the PI s responsibility to maintain the file, delegation of this role must be logged on the delegation log. The purpose of the trial master site file is twofold 1. To act as a working document for study personnel to ensure that designated, appropriately trained staff are working to the most up to date approved documentation. 2. To ensure a paper trail so that the study conducts can be enacted at a later date if required by the regulator or the scientific community. The file will be laid out as follows and contain the following sections and documents. 1. WORKING DOCUMENTS AND LOCAL STUDY PERSONNEL *Signed delegation /signature log -Trust delegation only to be used. -Appendix 1 File notes - appendix 2 *GCP Training records of study personnel Appendix 3 Up to date list of all patients on the study -Appendix 4 * Normal value ranges *These documents may be held in a generic working file if the PI has more than 5 open studies 2. STUDY DOCUMENTATION A copy of the current study protocol approved by the Ethics Committee 4

5 Previous protocol versions approved by the Ethics Committee - Marked Do not use. Copy of the current patient information sheet and consent form approved by the Ethics Committee Copy of previous patient information sheets and consent forms approved by the Ethics Committee - Marked do not use Copy of letter to GP informing of patients trial participation Copy of current case report form Copy of previous case report forms Marked do not use Copy of questionnaires Copy of previous questionnaires Marked do not use Copy of the Serious Adverse Event reporting documents If appropriate:- Advertisement for subject recruitment Investigator Brochure plus updates if appropriate 3. AGREEMENTS Clinical Trials agreement with sponsor signed by both the sponsor and the Trust Other contracts/agreements relating to the research Original Trust approval letter Trust approval letters for agreed amendments to study Insurance statement / Indemnity letters Letter from the sponsor stating role 4. ETHICS Copy of the Ethics Committee application REC Response letter giving approval to undertake the study SSI approval / R&D Approval application form Evidence of site specific approval Amendments to study documents Substantial amendment requests to regulators and Main Ethics Committee REC response letter giving approval to the substantial amendment / amendment Other amendment documentation letters from study centre etc. Additional documentation where we are acting as sponsor Any correspondence with the Ethics Committee following Initial application Any correspondence from the Ethics Committee following initial application Any correspondence with the Ethics Committee following amendment application Any correspondence from the Ethics Committee following amendment application 5. REGULATORY APPROVALS Regulatory approvals letters E.g. MHRA, ARSAC, NIGB (formally PIAG) Regulatory approvals amendments Additional documentation where we are acting as sponsor All correspondence with the regulators 5

6 6. SIGNIFICANT CONVERSATIONS AND CORRESPONDENCE RELATING TO THE CONDUCT OF THE TRIAL LOCALLY Communication log Appendix 6 7. CURRICULUM VITAE FOR ALL RELEVANT PERSONNEL Up to date (within the last 2 years) Curriculum Vitae for all relevant personnel (signed and dated) to include research training and GCP training These documents may be held in a generic working file if the PI has more than 5 open studies 8. AGREEMENTS WITH OTHER AREAS IN THE ORGANISATION WHOSE SERVICES THE STUDY WILL IMPACT UPON correspondence with evidence of agreement For example Laboratories X-ray Scanning Cardiology 9. CORRESPONDENCE FROM STUDY CENTRE ( and letter including a selection of study updates) All significant correspondence from the study Centre Individual patients research files Individual patient s research files are part of the Trust master file and should be kept as part of that file once the active follow up stage of the study is complete. They should contain Copy of the signed consent form Case report forms Pharmocovigilance forms (SAE s SUSARs Etc) Copies of other patient specific documentation relating to the research project OTHER SITE RESEARCH FILES ELECTRONIC SITE FILE Held on the Trust Network and available to all those involved in the study The Electronic site file is located in the... and is maintained by the Principle Investigator or delegate (as detailed on the delegation log). It contains all of the current approved versions of the study documents (the old versions are also available on an old version file). All staff who are working on the study should have access to this drive. If you require access to this drive please contact the R&D Manager on ext The Electronic site file folders will be held in the shared drive and called research projects and will be accessed as follows 6

7 Division Clinical Area Study Name this will be the study short title The individual study file will be laid out as follows:- Working documents: Current version of protocol, patient information sheet, consent form, CRF s and all other working documents will be held in this section. Appropriate documents must include the Trust s Logo. These will be version controlled. Old versions of Documents Old Versions of the working documents that have been approved by the Main REC will be held in this section. It is the responsibility of the person who manages the specific study on the shared area to transfer the documents to the old version section. Patient s details A list of all patients entered onto the study should be held on this drive. On completion of the study 3 years after the study has finished recruitment or completed active follow-up the data, It is the responsibility of the Trust archivist to burn the information held onto a CD and held in the Master Site file. Once the study is formally archived the CD will be destroyed. Research Patients Medical records The medical records of Patient s recruited onto treatment trials must be kept for at least 20 years following the end of active follow up. Patient s medical records will be flagged on the PAS system to ensure they are retained for 30 years. It will be the responsibility of the Principal Investigator or delegates identified on the delegation log, to flag the patient on the PAS system which will identify them has in a clinical trial. A list of patients recruited into the study will be held on the electronic study research file and the PI or designate will flag the patients on the PAS system. A designated member of the medical records team will have access to the Electronic research files. At the end of each study the PI or designate will inform the nominated person in medical records of the close down of the study. The nominated medical records staff will check that all patients are flagged as a second check The Archiving documents All study documents will be held in the department where they are generated in until they are officially archived. The study files will be kept in the department responsible for that file for 3 years following the last date of the last patient s active follow-up. 7

8 The R&D Manager will be the nominated archivist. He she will gather up all of the departmental research files pertaining to a particular study and having consolidated the records so that only one copy of each document is held. The documents will be archived using the assigned internal or external resource. Archiving will include the archiving of the individual patient research files. Data should be stored in a way that permits a complete retrospective audit if necessary. The archived documents will be kept for 5 years following the last marketing application or as directed in the protocol The files will be clearly marked as to what they are, which research project the relate to, the name of the local PI and the department and will be filed as follows Main site file Individual Patients research files Pharmacy files R&D files Other department s additional documents clearly marked as which department generated them. The study will be stored in their original format and boxed in a storage box. The box will be clearly marked with a storage number and the name of the study / studies stored in that box along with a list of the files stored. An archiving log will be held in the R&D office as a record of archived studies Appendix 6 8

9 v1.0 Appendix 1 CENTRE DELEGATION LOG 1 Name Role (eg. Research nurse, Co-investigator) Responsibilities Choose code(s) from the table below or specify. Signature Initials Involvement with Trials Date Date started stopped Principle Investigator Signature 2 Date 3 Date 4 Date 5 Date Responsibilities A Determine eligibility C Enter data and make corrections in Electronic CRF E Perform key trial measurements B Obtain Informed Consent D Lock electronic CRF data (sign-off) F Dispense trial medications G Prescribe Study Drug H I - J- K- L- M- N- O- P- Q- R- S- T- U- Date Page 9 of 14

10 v1.0 Appendix 2 File Note Date File note Signature Page 10 of 14

11 v1.0 Appendix 3 GCP Training Log Name of individual GCP Training Date Type of training Update training Comments Page 11 of 14

12 v1.0 Appendix 4 List of patients on the study Name of Study Principle investigator Contact details Patients individual study records are kept in Name of Patient Date of Birth Hospital Number Study Centre Number Treatment Arm Page 12 of 14

13 v1.0 Appendix 5 Communication Log. Date of communication Communication between Nature of communication Signature of person making entry Appendix 6 Page 13 of 14

14 v1.0 Archiving Log Date Box archived Number Study name and type of study Principal investigator and designation List of files held Main site file Patients individual research records Pharmacy files R&D files Other department files: Signed A copy of this entry will be kept in the Archiving box with the archived documents Page 14 of 14