Version 1.2 Effective date: 3 September 2012 Author: Approved by: Claire Daffern, QA Manager Dr Sarah Duggan, CTU Manager Revision Chronology: Effective Date Version 1.2 3 Sept 2012 Version 1.1 12 May 2010 Version 1.0 May 2008 Reason for change Format change. Amended process to inform WCTU which WMS trials require audit. Change WMSCTU to WCTU. Addition of section references for ICH and MRC GCP definition of audit. Amendment to list of report recipients. Page 1 of 5
1. Purpose This Standard Operating Procedure (SOP) describes the audit procedures of Warwick Clinical Trials Unit (WCTU) acting on behalf of the University of Warwick as a Sponsor organisation. This SOP specifically describes the processes for selecting studies to be audited, the procedures for carrying out audits and reporting audit findings. It also describes the requirements for investigators to respond to audit reports and implement corrective actions. 2. Background The audit process is defined by both ICH (section 1.6) and MRC (section 1.2) GCP guidelines 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, sponsors Standard Operating Procedures (SOP s), Good Clinical Practice (GCP) and the applicable regulatory requirements. As a Sponsor organisation (an institution that takes responsibility for initiation, management and/or financing of a clinical trial), the University of Warwick is legally responsible for auditing research practice and assuring adherence to current legislation and guidelines. As such, it is necessary to audit research for which the University is the lead sponsor against the standards of the Research Governance Framework 2005 and the Medicines for Human Use (Clinical Trials) Regulations 2004, where applicable, and against the quality systems of Good Clinical Practice intrinsic to the regulations. The purpose of an internal audit is to: Ensure participants rights and welfare are being adequately protected Assist researchers with compliance to regulatory requirements and University policy Assure regulatory compliance Prepare researchers for potential future external regulatory inspections Aid in identifying and correcting problem areas and provide suggestions to improve quality. 3. Procedure 3.1 Who? The Clinical Trial Unit s Quality Assurance (QA) Manager will conduct audits on behalf of the University. The Clinical Trials Unit Manager will provide the QA Manager with a list of all trials being conducted within the unit on an on-going basis when funding for a new trial is confirmed. Page 2 of 5
The Warwick Medical School Research Ethics and Governance Manager (WMS REGM) will maintain an on-going record of all trials within WMS and supply this list to the QA Manager each quarter or on request. 3.2 When? The QA Manager will undertake an audit of all the randomised trials being sponsored or co-sponsored (where specified in the contract) by the University of Warwick at least once in their lifetime. Further audits may take place if there are specific concerns or the trial duration is greater than five years. Trials may also be audited on a voluntary basis (requested by the researcher) or where there is a suspicion of non-compliance to regulations. The time-point of audit will be within 6-12 months of initiation of recruitment, thus allowing audit of consent, data recording etc. 3.3 How? 3.3.1 Letter of notification The QA Manager will notify the Chief Investigator (CI) that their trial is due for audit via a standard letter which will outline the scope and objectives of the audit, provide a list of the documents that will be required and state the estimated time the audit is expected to take. The letter will also identify the people who may be required and how findings will be reported back. The CI will be contacted following receipt of the letter to agree a mutually convenient date for the audit to take place. This date will be confirmed with the CI by letter. 3.3.2 Audit visit The audit visit will commence on the agreed date and information will be assessed and recorded using a standard template report form. Any questions that are identified at the time of the audit will be raised with the CI or delegated team member during the audit visit. Audit activities include (but are not restricted to) a review of: Facilities Staff training records Essential documentation Consent forms and process Drug storage and accountability (if applicable) 3.3.3 Written report to CI of audit findings The QA Manager will send the CI a written report within 28 days identifying areas of non-compliance. Recommendations for corrective actions and timelines will be detailed along with who is responsible for completing each action. A copy of the report will be sent to the Dean of the Medical School, Director of WCTU, relevant Head of Division (e.g. Health Sciences, Reproductive Health), the Director of Research Support Services and WMS REGM. Page 3 of 5
Audit visit findings will be graded using the following criteria: Major: a finding defined as one with the capacity to put participants at immediate risk or directly undermine the integrity of the entire trial. For example: Where evidence exists that the safety, wellbeing, rights or confidentiality of trial participants has been (or has significant potential to be) jeopardised. Where approval of the trial has not been sought or granted from one or more regulatory body (e.g. Ethics committee, MHRA) but the trial has commenced regardless. Where procedures not included on the consent form are being performed or new procedures have been introduced but participants have not been asked to re-consent. Where significant amendments have been made to the protocol but no new request for approval has been submitted. Where reason has been found to cast serious doubt upon the accuracy and/or credibility of trial data. Moderate: a finding defined as one that compromises the integrity of a certain component (or components) of the trial. For example: Where there has been a significant and unjustified departure from UK regulations or GCP guidelines e.g. failure to provide participants with a copy of their consent form or Participant Information Sheet (PIS). Where there have been a number of minor departures from the UK regulations or GCP, suggesting a systematic quality assurance failure. Minor: any other audit findings defined as those where the integrity of the trial is not directly compromised but which represent a lack of due diligence on behalf of trial staff towards the conduct of the trial. For example: Findings which demonstrate that no definite document management systems are in place at site. Where there has been a failure by trial staff to inform the relevant authorities of amendments to start/stop dates or study specific documents. 3.3.4 Response to report and follow up It is the CI s responsibility to ensure the required actions are taken to remedy any issues detailed in the audit report. The CI must respond to the audit report within 28 days and corrective actions to be made in an agreed, specified time frame. The response should be sent to the QA Manager and copied to the WMS REGM. A follow up visit may be made to the site to confirm that all the necessary actions have been taken. Page 4 of 5
Abbreviations: CI Chief Investigator GCP Good Clinical Practice ICH International Conference on Harmonisation MHRA Medicines and Healthcare products Regulatory Agency MRC Medical Research Council PIS Patient Information Sheet QA Quality Assurance REGM Research Ethics and Governance Manager SOP Standard Operating Procedure WCTU Warwick Clinical Trials Unit WMS Warwick Medical School Page 5 of 5