SOP Monitoring

Transcription

1 Monitoring Author: Sandra Schrek Signature: Date: Approved by: Zoe Doran Signature: Date: Effective date: 11 / 04 / 2008 Document Revision History Version Effective date Changes 01 New SOP Page 1 of 8

2 1.0 Scope This Standard Operating Procedure (SOP) has been written in order to conduct clinical studies according to the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use Good Clinical Practice (ICH-GCP) guidelines. This SOP describes in particular the procedure for monitoring clinical trials sponsored by the European Group for Blood and Marrow Transplantation (EBMT). The purpose of monitoring is to assure that the trial is being conducted according to the approved protocol, GCP, and all applicable laws. And to assure that the facilities and staff at the investigational site continue to be adequate for the conduct of the trial. Clinical trial monitoring requires data collection and analysis throughout a project to ensure appropriateness of the research and project design, validity and integrity of the data, and protection of human subjects. 2.0 Abbreviations CRF Case Report Form CTO Clinical Trials Office CV Curriculum Vitae EBMT European Group for Blood and Marrow Transplantation GCP Good Clinical Practice ICH International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use ISF Investigator Site File MVR Monitor Visit Report PI Principal Investigator Page 2 of 8

3 PIL SAE SDV SOP TMF Patient Information Leaflet Serious Adverse Event Source Document Verification Standard Operating Procedure Trial Master File 3.0 Responsibilities Monitoring activities may be undertaken by dedicated Clinical Research Associates, whose primary role is to monitor studies, other trial management staff, who are seconded to undertake some or all monitoring activities, or statistical staff implementing a remote monitoring plan. The allocation of monitoring duties may be influenced by the resources available to support the study and may change during the course of the trial. However, anyone who undertakes the role of a monitor must have relevant experience and/or training to undertake this activity. 4.0 Introduction All clinical trials require monitoring, and the method chosen must be commensurate with the degree of risk. Prior to the commencement of accrual at an institution, each institution must be initiated. For further information please refer to SOP 115 Initiation. Throughout the period that the clinical trial is conducted at an Institution, the Sponsor is obliged to conduct monitoring visits to review study data and ensure that the trial is being conducted in compliance with the approved protocol, ICH-GCP, and all applicable laws. The frequency of monitoring will be specified by each individual protocol but will at a minimum conform to the standards laid down by law. The extent and nature of monitoring is determined prior to initiation of the trial and based on considerations such as the primary and secondary objective(s) and their associated Page 3 of 8

4 endpoints, design, treatment plan, safety considerations and available resources. In addition it may be influenced by the prior experience of the investigator/institution s previous or current trials. Each visit must be documented and all documentation providing evidence of monitoring procedures must be archived in the Clinical Trials Office (CTO) assigned to the study. The aims of a monitoring visit are to verify that: The rights and well-being of human subjects are protected. The conduct of the trial is in compliance with the currently approved protocol/amendment(s), in accordance with the principles of ICH-GCP and with the applicable regulatory requirement(s) specific to the country in which the trial is being conducted. The reported trial data are accurate, complete, and verifiable from source documents. To identify any problems with the conduct of the study and implement a project plan to resolve them. To clarify any queries. The local PI had completed all the necessary paperwork to achieve regulatory, ethical compliance and obtained any relevant local approvals prior to commencing the accrual of subjects in the clinical trial. 5.0 Procedure The procedure can be broken down into three phases; i.e. preparation, the monitoring visit and follow-up. 5.1 Preparation for a Site Visit Schedule a visit including expected duration with investigator(s) and trial personnel, including pharmacist if relevant. Page 4 of 8

5 Send confirmation letter or to investigator giving time, date and duration of visit and outlining purpose of visit and items for discussion. Identify materials or information that the investigator is expected to provide and personnel who should be present. Do the same for the Pharmacist if relevant to study Review all essential documents related to the trial registration and regulatory/ethical approval of the study. Identify any that are not yet on file centrally and need to be collected from the centre or any documents that may need to be distributed to trial centre (e.g. any applied for by the Sponsor). Review previous monitoring report(s) if relevant (or initiation report if first monitoring visit), recent telephone contact reports or s with the centre and establish outstanding actions. Review current status of the study. Number of patients enrolled. Identify CRFs due for monitoring and collection. Review any SAEs associated with the centre. Check for outstanding data queries for the centre. Gather documents needed for undertaking of the monitoring visit (e.g. previous Monitor Visit Report (MVR), extra copies of all logs (e.g. screening, enrolment, consent form) in case update needed). 5.2 The Monitoring Visit Sign site visit log. Assemble all required trial documentation. o Investigator Site File (ISF) o Completed CRFs o Completed CRFs, edited by investigator since last visit. Review ISF: the ISF is the main site located repository for the essential documents for the conduct of a clinical trial. The contents that must be filed in the ISF are specified in SOP 310 Trial Master File. Page 5 of 8

6 o Ensure that the ISF is complete and up-to-date, adding documents being delivered during this visit, identify any deficiencies. o Check if any documents have been added to the file by the site since the last Monitoring Visit and photocopy if copies are required at for the files at the coordinating clinical trials office. o Check if any changes have occurred in site personnel, update roles and responsibility logs and signature log if relevant. Obtain CVs for any new staff and update investigator Agreement or Protocol signature page if required by any change in site personnel. Review all trial subject related logs. Monitor completed CRFs verifying the data against the source documentation in the patient s notes (SDV). o Check that Inclusion/Exclusion Criteria have been met by any new subjects enrolled by checking data entered on relevant pages of CRF against the information recorded in the subject s case notes. o Note any non-compliance with Entry Criteria to address with investigator. o Verify that written, informed consent was obtained from each subject prior to entry into the trial, check that current version of the consent form, valid at the time of subject enrolment was used. If the PIL/Consent form has been amended, ensure that all subjects still on study at the time that the revised consent was approved and current patients are re-consented with the new form. o Verify that subject was treated as per protocol, if randomised trial check subject received allocated arm of the trial. o Verify the percentage identified for the protocol of Adverse Events recorded on the CRFs and 100% of any Serious Adverse Events. o Source verify 100% of endpoints of study e.g. response to treatment, relapse-free survival. o Check CRFs for consistency of administrative details e.g. subject initials, unique identification number. o Note any discrepancies or protocol violations to discuss with the investigator and other staff. Page 6 of 8

7 Visit Pharmacy, if relevant, to check drug accountability data o Inventory supplies with Clinical Trials Supplies Log/Dispensing Log. o Confirm that storage requirements are met (e.g. Refrigerated). o Ensure adequate supplies. o Check drug expiry dates and document. o Check all patients to whom clinical trials supplies have been dispensed are study patients. Review monitored CRFs with Research Nurse and/or Data Manager. If possible have staff make corrections during the visit. Review any outstanding corrections from previous visits. NB Monitors may not make corrections, under any circumstances, to CRFs. Review supplies of all study related materials and make a note of any deficiencies that need to be addressed. Meet with study investigator to review study progress, in particular accrual and discuss any issues. Ensure he is aware of any reporting/submission dates that are due in the near future. Update investigator on study progress in general. Make provisional arrangements for the next visit. Prepare any Note(s) to File required to document 5.3 Follow-up Complete MVR within two weeks of monitoring visit and send to the Clinical Trials Supervisor for sign-off. He sends a copy of the signed MVR to the site Send follow-up letter to investigator(s)/study personnel within two weeks of visit outlining general findings. Provide follow-up information and/or request any documentation that is outstanding from the site. File the Monitoring visit report and follow-up letter in central files. Page 7 of 8

8 6.0 References - ICH Harmonised Tripartite Guideline for Good Clinical Practice (GCP) EU Clinical Trials Directives2001/20/EC and 2004/28/EC - National Institute of Health and the National Institute of Allergy and Infectious diseases website: and - SOP 115.XX Initiation 7.0 Appendices Not applicable. Page 8 of 8