Risk Assessment and Monitoring

Transcription

1 Version 1.3 Effective date: 25 May 2012 Author: Approved by: Claire Daffern, QA Manager Dr Sarah Duggan, CTU Manager Revision Chronology: Effective Date Version May 2012 Version January 2010 Version January 2008 Reason for change Renamed as includes risk assessment information. RSS web link updated. Minor text amends in section 3. Templates added. Bi-annual review: RSS web page link updated. Bi-annual review Format change. Version 1.0 March 2006 Page 1 of 6

2 1. Purpose The purpose of this Standard Operating Procedure (SOP) is to describe how to decide the level of monitoring that is appropriate for a trial, based on the risk assessment, and the range of procedures available to meet that requirement. You are advised to refer to the University of Warwick Research Code of Practice available on the Research Support Services website: 2. Background Risk assessment is a systematic method of estimating the likelihood of adverse effects that may result from exposure to certain hazards. The assessment should identify and document suitable control measures to minimise any hazards/risks identified. Considerations for inclusion in a trial risk assessment should include (but not be limited to) ethics, data protection and confidentiality, trial population, type and complexity of the intervention, recruitment issues etc. The trial monitoring plan should be based on the level of risk associated with each trial. Monitoring is defined by International Conference on Harmonisation Good Clinical Practice (ICH GCP) section 1.38 as the act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded, and reported in accordance with the protocol, Standard Operating Procedures, Good Clinical Practice, and the applicable regulatory requirement(s). The purpose of monitoring is defined by ICH GCP (5.18.1) as verifying that: 1. The rights and well-being of human participants are protected. 2. The reported trial data are accurate, complete, and verifiable* from source documents. 3. The conduct of the trial is in compliance with the currently approved protocol/amendment(s), with GCP, and with the applicable regulatory requirement(s). *This does not imply that every item of data recorded must be supported by a source document or checked. Where there are original documents the trial data should be in agreement with the information they contain. Where the Case Report Form (CRF) is the source document (e.g. information collected directly from the participant and not recorded elsewhere) then the training of the persons collecting and recording those data and clearly documented procedures are crucial. The monitoring required for each trial will vary according to the nature of the trial. The level of monitoring required will be based upon considerations such as the objective, Page 2 of 6

3 purpose, design, complexity, blinding, size, and endpoints of the trial. In general there is a need for on-site monitoring, before, during, and after the trial; however central monitoring in conjunction with procedures such as investigators training and meetings, and extensive written guidance can assure appropriate conduct of the trial in accordance with GCP. Statistically controlled sampling may be an acceptable method for selecting the data to be verified (ICH GCP ). 3. Procedure 3.1 Who? It is the Sponsor s responsibility to ensure that arrangements are in place before the trial begins and to allocate responsibilities for monitoring during the research. 3.2 When? A risk assessment should be conducted, and the extent and nature of monitoring should be determined, prior to the trial starting. 3.3 How? Specific Procedures Determine the extent and nature of monitoring required, based on the risk assessment Ensure arrangements are in place to allocate responsibilities for monitoring the research This should be done before the trial begins Record monitoring visits and outcomes, and ensure there is clarity regarding who will review monitoring reports Provide procedure for dealing with actions arising from monitoring visits Page 3 of 6

4 Risk Assessment Risk assessment should be carried out as early as possible in the trial design stage to identify potential hazards. It is good practice to undertake the risk assessment as a team so everyone is aware of all the potential hazards at each stage of the trial and define actions which may be taken. For each hazard, the following should be considered: a) The associated risks to the particular trial; b) The potential consequences; c) Reasonable steps to reduce the risks by (1) reducing the probability of the hazard occurring or (2) minimising its adverse consequences. The use of a risk ranking matrix allows hazards identified to be graded by their potential severity and the likelihood of occurrence. The risk can be categorised as low, medium or high and appropriate actions defined to manage the risks. A Warwick Clinical Trials Unit (WCTU) risk assessment template is available. The Medical Research Council/Department of Health (MRC/DH) joint project also produced a document on clinical trial risk assessment which is available via: Monitoring Plan The aim of monitoring is to improve quality and promote high standards, identify noncompliance or research misconduct/fraud, and to ensure participant safety and adherence to regulations. There are many different ways in which a trial may be monitored, and the monitoring plan will be based on the trial design (to inform the methods used), and a risk assessment (to determine the intensity and focus of the monitoring) carried out for each trial. The monitoring procedures for each trial should be documented, to include: The extent and nature of monitoring to be employed The responsibilities of those involved The procedures for monitoring reports and for dealing with issues raised. Various approaches may be used e.g. trial oversight committees, central monitoring, on-site monitoring and site self-monitoring checks. A WCTU Monitoring Plan template is available. The MRC/DH joint project on good practice in clinical trials with medicines provides a trial monitoring option checklist of ways a trial may be monitored; Page 4 of 6

5 This checklist may be used prior to the start of the trial to determine which features of monitoring are essential, desirable, unnecessary or not applicable to a particular trial. Other alternative methods may be applicable. The risk assessment and monitoring plan should be filed in the Trial Master File (TMF). For clinical trials of Investigational Medicinal Products (CTIMPS), the protocol should include details of the monitoring policy to be applied (Medicines for Human Use (Clinical Trials) Act 2004). For CTIMP Type 1 notifications, a risk assessment and monitoring plan are required as part of the submission to the Medicines and Health Care products Regulatory Agency (MHRA). For more details refer to SOP 5 Regulatory Approvals and Communications and the MHRA website: Submittinganotificationforatrial/Submittinganotificationforatrial/Generalinformation/inde x.htm Responsibilities and training of monitoring staff Trial monitoring procedures should be described in such a way as to make clear the responsibilities of the staff involved, including their organisation training and relationship to other trial staff, the arrangements for central monitoring, the frequency and nature of site visits (if required) and how the results of monitoring inform other activities such as the training of personnel at study sites. To monitor a trial successfully requires both relevant scientific and/or clinical knowledge, and appropriate training. It is recommended that these be documented (e.g. in the CV and/or training records held by the individual or personnel department) Monitoring reports Monitoring visits and other monitoring procedures should be recorded. Visit reports would typically include the date, site, name of the monitor, and name of the investigator(s) or other individuals contacted, as well as a summary of what was reviewed. The monitor should record significant findings, any deficiencies detected, conclusions and any recommended actions. A Monitoring Visit Checklist/Report template and a visit report letter template are available. Page 5 of 6

6 3.3.6 Procedures for dealing with the issues raised by monitoring It should be clear by whom monitoring reports are to be reviewed. Any required actions detailed in the monitoring report should be dealt with promptly by the member of staff identified in the report. List of abbreviations CRF Case Report Form DMEC Data Monitoring & Ethics Committee DH Department of Health GCP Good Clinical Practice GP General Practitioner ICH International Conference on Harmonisation IMP Investigational Medicinal Product MHRA Medicines and Healthcare products Regulatory Agency MRC Medical Research Council ONS Office for National Statistics TMG Trial Management Group TSC Trial Steering Committee WCTU Warwick Clinical Trials Unit Available Templates 18-1 Risk Assessment Template 18-2 Monitoring Plan Template 18-3 Monitoring Site Visit Checklist/Report Template 18-4 Monitoring Site Visit Report Letter Template Page 6 of 6