Standard Operating Procedure (SOP) Research and Development Office Title of SOP: Routine Project Audit SOP Number: 6 Version Number: 2.0 Supercedes: 1.0 Effective date: August 2013 Review date: August 2013 Author: Approved by: Alison Murphy, Research Manager Endorsed by Paul Carlin Dr David Hill Signed: Date: 01 August 2013
Version History: Version No. Date Author Reason for Change 1.0 Oct 2007 Katrina Hughes N/A 2.0 Aug 2011 Alison Murphy Updated to reflect new SOP layout. Revised title. Method of selecting projects included. Audit process and template updated. Document Number: SOP/RAD/SEHSCT/006 Page 2 of 23
Table of contents 1. Introduction 2. Objective 3. Scope 4. Procedure 4.1 Selecting Projects for Routine Audit 4.2 Initiating the Audit 4.3 Conducting the Audit 4.4 Writing the Audit Report 5. Regulations, Guidelines, references, SOP Links etc 6. Appendices 6.1 Audit Proforma Document Number: SOP/RAD/SEHSCT/006 Page 3 of 23
1. INTRODUCTION An audit is: 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 Standard Operating Procedures (SOPs), Good Clinical Practice (GCP) and the applicable regulatory requirements. (ICH GCP 1.6) Audit of research within the Trust is an important function of research governance. It enables the Research Office to assess the conduct of research in the Trust, and to identify potential and actual problems and address the training needs of research staff. Throughout the audit, general information exchange between the auditor and the institution being audited is acceptable and essentially is used as an evaluation tool. This ensures that research conducted within the Trust continues to be of a high standard and we continue to provide a supportive and proactive service to Trust research staff. It also ensures that the safety of our patients and service users is maintained. An audit is an informal planned process and can take place prior to, during or after the patient recruitment phase. An internal audit is often undertaken prior to an external inspection. There are two types of Audit; Routine Random Active Project Audit and For Cause Audit. This SOP covers Routine Random Active Project Audit, There is a separate SOP for For Cause Audit (SOP 14) 2. OBJECTIVE This SOP describes the Routine Random Active Project Audit procedures of South Eastern Health and Social Care Trust Research Office (SEHSCT). This SOP specifically describes the processes for selecting those studies identified as requiring a routine random project audit. This SOP also describes the requirements and timelines for investigators to respond to these types of audit reports and implement corrective actions. 3. SCOPE This SOP applies to all research projects taking place within the South Eastern Health & Social Care Trust Document Number: SOP/RAD/SEHSCT/006 Page 4 of 23
4. PROCEDURE 4.1 Selecting Projects for Routine Audit When a research project is being granted final permission the required audit schedule should be agreed, depending on risk. High risk projects such as clinical trials of investigational medicinal products (CTIMPs) for which the Trust is sponsor, research involving invasive techniques, etc. would normally take precedence over relatively lower risk research such as questionnaire or non invasive projects. It may be agreed that a particular project will be subject to an audit over its lifetime or other projects will just be randomly selected. 4.2 Initiating the Audit A standard letter is sent to the Chief/Principal Investigator for the trial informing them of the intention to audit the project. A blank joint audit tool should be attached for the researchers information and preparation. A follow-up phone call should be made a few days after sending the letter, to confirm receipt of letter and awareness of audit. Prior to an inspection taking place a coordinator should be appointed, for example a research registrar/research nurse to use as a point of contact as PIs/CIs often delegate audits to their staff. During the call, questions can be answered and a date arranged to conduct the audit. Suitable accommodation should be identified and booked i.e. a space to review all documents etc. 4.3 Conducting the Audit The Research Manager is ultimately responsible for conducting research governance audits. An audit proforma (see Appendix1) needs to be completed for the audit. The audit will normally take place in the department where the research project is conducted. A random sample of 10% of Case Reports Forms (CRFs) and medical case notes should be requested. The Master File for the project should be scrutinised. However, not all files will contain all documents. The following would usually be expected: Curricula vitae of all staff Signature sheet Adverse event log Code break procedure for randomised controlled trials Document Number: SOP/RAD/SEHSCT/006 Page 5 of 23
Screening log Randomisation log Copy of the protocol Delegation log ( for projects with more than 2 staff) Ethics application and opinion letter Clinical Trial Authorisation (if appropriate) Copies of all correspondence R&D approval letter Blank forms (e.g. consent forms, patient information sheets) The Research Office project file should be taken to the audit. All documents in the Master File should be compared with those in the R&D Project File to ensure that they are the same version (version numbers should be clearly marked on the documents). Any deviations from the protocol or changes should be initialled, dated and signed. All documents (screening logs, randomisation logs, etc) should be accurate, legible and timely. The ethics application in the Research Office file should be compared with the copy in the Master File to ensure they are the same version. Ethical opinion letter should be checked to see if any amendments or revisions have been recommended evidence of implementation of such amendments should be found. All CRFs should have a completed consent form. The consent form should be signed by the research subject and the person taking consent on the same date. It is not acceptable to have different dates on consent forms. All medical case notes should have copies of GP letters (if applicable) informing them of the subjects participation in the research. The number of patients recruited should be assessed in relation to the length of time the project has been active and the overall predicted recruitment. Projects with a low recruitment rate or high drop out rate should be noted. All medical case notes should have Research stickers on the inside cover. Patient information sheets should also be checked to ensure the version number is the same as the version submitted for ethical approval. Consent forms and patient information literature should be printed on Trust headed paper. Check that that this done. Also check that the Trust notepaper is not out of date (i.e. it has the current Chief Executive name) All CRFs and medical case notes should be stored in locked filing cabinets in a lockable office. The storage of CRFs needs to be checked. There should be limited access to this data. Document Number: SOP/RAD/SEHSCT/006 Page 6 of 23
All computer based data should be password protected and there should be limited access to this data. For CTIMPS it must be ensured that all patients hospital notes are available for source documentation verification. This should include up to date annotations, GP letters, laboratory results, x-ray results etc. related to participation in the clinical trial. If there are legitimate reasons why a patient s hospital notes cannot be available, this must be explained in advance of the audit. The following personnel, where appropriate, should be available to answer questions and to attend the final meeting before the Auditor leaves the site: Chief/Principal Investigator and research personnel Personnel from other departments involved in the audit/inspection such as pharmacy, laboratory (departments should be fore-warned if the auditor /inspector intends to visit) When the auditor is satisfied that all documentation has been scrutinised and the audit form has been completed, the report should be written in the Research Office. 4.4 Writing the Audit Report The audit report should be written as soon as possible after the audit, but within two weeks from the initial audit. The following information should be included at the start of the report: Full title of the project being audited R&D reference number REC reference number Sponsor ID Chief Investigator Principal Investigator CTA Details (if applicable) An overview of the project The report should be written as follows: The detailed audit plan A review of the evidence collected Areas of good practice A discussion of any conclusions drawn from the audit A list of identified gaps in compliance An assessment of how well regulatory requirements have been met Recommendations for change in practice to confirm to regulation A date for recommended review Document Number: SOP/RAD/SEHSCT/006 Page 7 of 23
A copy of the finished report should be sent to the following people: Director of R&D Chief Investigator Principal Investigator If the Audit uncovers a serious breach of GCP/Protocol the Research Manager is bound by law to inform the MHRA and Main REC. The Breach must be likely to affect to a significant degree the safety or mental integrity of the subject, Trial or scientific value of the Trial. See SOP 23. A copy of the report should be maintained in the Research Office. The Chief Investigator of the study is expected to respond to the audit report within 1 month and corrective actions made within agreed timelines. If required a follow up visit can be arranged to check that the recommendations made by the audit report have been implemented. If the recommendations made by the audit report are not been implemented, it may be necessary to suspend recruitment to the research project until the recommendations are implemented. This needs to be discussed with the CI and the R&D Director. 5. REGULATIONS, GUIDELINES, REFERENCES, SOP LINKS etc. Department of Health Research Governance Framework for Health and Social Care 2 5 (2 nd Edition) UK Clinical Trials (Medicines for Human Use) regulations 2004; ICH< GCP Guidelines 2006 Linked to: SOP14 For Cause Project Audit SOP23 Notification of Serious Breaches of GCP 6. APPENDICES 6.1 Audit Proforma Document Number: SOP/RAD/SEHSCT/006 Page 8 of 23
Audit Proforma Routine Random Audit Site Visit date: Chief Investigator: Contact: EudraCT Number (if applicable) Purpose of audit: Routine/For Cause Study title: Project ID: R&D REC Sponsor: Study Site: Stage of Project: Initiation/During/Closure Date of Ethical Approval and the Ethics Committee approval letter: Is there a CTA? Date of CTA: If CTA is not necessary is there written evidence that this is the case? Date of R&D Final Permission at this site: 1. Approvals Ethics Yes Partial No N/A Comments Does the ethics submission match that held by the Trust R&D Office? Is there a copy of the locked ETHICS Committee application available? Is there present any correspondence with the Ethics Committee following the application, e.g. application for approval of a substantial amendment? Is there evidence of implementation of a substantial amendment, Document Number: SOP/RAD/SEHSCT/006 Page 9 of 23
including informing the patient or re-consenting if appropriate? Is the Site Specific Assessment documentation present and correct? Period of approval: Did the study commence within the year of Local REC Approval? What is the actual /expected end date for this study: Have annual progress/safety reports been sent to ethics? Clinical Trials Authorisation Are there copies of submission to the MHRA for a CTA? Is CTA present and correct? Have any remarks made by MHRA following CTA application been addressed? R&D Approval Is this the lead site for the study? If so are there approvals for all participating sites? Is there evidence of an appropriate identified sponsor? Is there a copy of the R&D Application? Is the Trust R&D permission letter present and correct? Has R&D been informed of the actual start date? Do R&D have contact details for the local Document Number: SOP/RAD/SEHSCT/006 Page 10 of 23
study co-ordinator / PI? Do all local staff involved in the study have documentary evidence of relevant training? ( i.e. GCP) Do members of the research team who are not NHS employees of this Trust have honorary contracts in place? 2. Trial Master File Trial Master File Yes Partial No N/A Comments Is there a Trial Master File available? Are the following included: A copy of the currently approved protocol, signed by the investigator ( dated prior to implementation) Previous protocol versions, signed and dated Copies of all amendments Approval of amendments by regulatory bodies (Ethics, MHRA) The Study sponsorship agreement Any other agreements where the Trust is not the Sponsor Any other financial agreements or contracts ( i.e. with a University) Insurance and Indemnity statements Copy of the Clinical Trials Agreement, signed by the relevant Document Number: SOP/RAD/SEHSCT/006 Page 11 of 23
personnel and all documents concerning amendments Copy of Trust R&D Approval ARSAC approval GTAC approval Copy of the Ethics application and favourable opinion letter Copy of currently approved Patient Information Sheet Copy of currently approved Consent Form ( referencing current version of Patient Information Sheet) Advertisement of subject recruitment Copy of currently approved GP letter Sample case report form Laboratory documents including ranges and laboratory accreditation Code breaking information and procedures Randomisation Log CVs of all staff: Signed and dated within the last 12 months Including GCP Relevant research training R&D Training events Research Document Number: SOP/RAD/SEHSCT/006 Page 12 of 23
related publications Current Investigator s brochure ( plus updates) Monitoring Log and reports Copies of yearly /interim study reports submitted to Trust R&D All critical communications, such as letters, meeting reports, notes of telephone conversations filed in a logical manner Adverse Event/ SUSAR log for the site Record of Serious Adverse Events at other sites Copies of annual and interim reports to competent authority and ethics committee, or normal Trust system Copies of annual safety reports Delegation log, including signature sheet Are all researchers on the delegation log registered with the R&D Department Completed subject participation and screening log If the main site of a Multi Centre Trial does it include: Ethical approval R&D approval Delegation logs for all sites Document Number: SOP/RAD/SEHSCT/006 Page 13 of 23
Will new equipment be brought in to the Trust for the purpose of the study? Will it be regularly calibrated? Insured? If applicable, electrically tested? Final report to appropriate authorities 3. Patient Information and Consent Patient Information Is the Patient Information Sheet used in the study the currently approved version (REC and R&D)? Does it match the ethics submission? Are there copies of previous Patient Information Sheets and Consent Forms as approved by the Ethics Committee? Out of hours contact information provided to patients? Does any other material given to patients have ethical approval to be used? Is Trust headed paper used? Is the Consent Form the current ethically approved version? Are all consent forms signed and dated by the subject and the Yes Partial No N/A Comments Document Number: SOP/RAD/SEHSCT/006 Page 14 of 23
person taking consent? Do the dates of the signatures between the patients and consent taker match? How has the patient checked (initialled or ticked) each statement? Is the Consent Form on Trust headed paper? Are all original Consent Forms, filed in recruitment order in the Site File? Is there a copy of the consent form In the CRF? In the case notes? In the master file? For the subject to keep? Are consent forms present for all those listed on the participation log? Is consent given prior to study procedures? Have any specific procedures prescribed by the protocol / ethics been adhered to? Have appropriate measures been taken for a paediatric setting? If the protocol has been amended has re-consenting been undertaken and documented appropriately? Document Number: SOP/RAD/SEHSCT/006 Page 15 of 23
Document Number: SOP/RAD/SEHSCT/006 Page 16 of 23
4. Recruitment Recruitment Yes Partial No N/A CComments How many patients to date at this Trust: Have been screened: Have been enrolled: Have been consented: Have been withdrawn: Do participants looked at meet the protocol inclusion and exclusion criteria? If not has this been correctly documented and approved? Document Number: SOP/RAD/SEHSCT/006 Page 17 of 23
5. Pharmacovigilance Pharmacovigilance Yes Partial No N/A Comments Is there any documented system for identifying, assessing and recording serious adverse events as required by the trials regulations, protocol and Trust? Have any SAE/SUSARs occurred in this Trial? Is there evidence that SAEs have been identified, assessed for causality, recorded and reported as required by the MHRA, REC, Sponsor and R&D in this Trust? Are reported Serious Adverse Events verifiable against patient records (i.e. adequately recorded in the source documents)? Have there been any Adverse Events that have been discovered during routine monitoring? ( this should be documented and reported to the Sponsor) Are deviations from the protocol and non compliance with legislation and guidance documented and resolved? Does the study have a data monitoring committee? Has an Annual Safety Report or end of study report been submitted to the MHRA on time? Document Number: SOP/RAD/SEHSCT/006 Page 18 of 23
(Number and date submitted) 6. Record Legibility Legibility Yes Partial No N/A Comments Has the investigator or person designated by the appropriate investigator made appropriate corrections, additions, or deletions that are dated and initialled by the investigator or person designated by the investigator? Do Case Report Forms and other study documents such as data collection sheets contain any entry error, omission or illegibility? Have all those that have recorded information been delegated to do so by the investigator and recorded in the delegation log? Document Number: SOP/RAD/SEHSCT/006 Page 19 of 23
7. Data Protection Data Protection Yes Partial No N/A Comments Is all study hard copy documentation stored in a restricted area? Is study documentation such as questionnaires and other data collection instruments designed in such a way that they do not carry patient identifiable data? Are computer records and files containing identifiable data stored on a remote and secure server? If not, why not? Is the emergency recovery procedure for retrieving data available ( e.g. Trust IT policy) Is access to electronic study records and files password protected? Are electronic data files for analysis anonymised? Are the data protection arrangements as approved by the REC? Will any documentation be archived off site? If yes, are details logged with the R&D Office? Document Number: SOP/RAD/SEHSCT/006 Page 20 of 23
8. Patient Health Records Patient health records Is a research consent form in the clinical notes ( signed and dated)? Does the consent form match the copy held in the CRF? Is consent entered into the electronic register? Are there consent forms relating to other concurrent research in the patient records? (If Yes, indicate which studies and date of signing) Is it stated in the patient health records that the patient has received a copy of the patient information sheet and signed consent form? Is a label attached to the health records in an appropriate place stating that the patient is taking part in a clinical trial? Is withdrawal from the study documented ( where applicable)? Are reported Serious Adverse Events verifiable against patient records? Is there present in the patient health records a letter (to GP) informing of patients trial participation? Yes Partial No N/A Comments Document Number: SOP/RAD/SEHSCT/006 Page 21 of 23
9. Human Tissue Act Documentation Yes Partial No N/A Comments Are samples used in this project from the : Living Deceased Are the consent forms used compliant with the HTA code of practice? Are consent forms easily accessible to those involved in the trial? If required, are Material Transfer Agreements in place containing details of: Consent procedures Tracking Use Disposal or return Are consent procedures as set out in the protocol, ethically approved and compliant with HTA codes of practice? Does each sample have a unique identifier code assigned to it? From the code and records system, I can find the following: When the body parts, tissue or cells were acquired Where from That consent was obtained Document Number: SOP/RAD/SEHSCT/006 Page 22 of 23
What samples have been used for If samples have been transferred to another establishment ( where and when) Are systems in place to facilitate HTA communications, NPSA alerts etc? Is there evidence of risk assessments for all practices and process involving samples? Are the premises and procedures compliant with Trust Health and Safety policies and controls? Document Number: SOP/RAD/SEHSCT/006 Page 23 of 23