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Thread: MHRA produced FAQs for monitoring

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  1. #21
    20. What activities comprise “central monitoring” of a clinical trial and should they be documented?

    Central monitoring activities, focussing on the areas that matter as identified in the monitoring strategy could be undertaken by numerous roles and across various departments, for example clinical operations, study management, data management, statistics, medical monitoring etc. with close co-operation where appropriate. It is recommended that where the sponsor is undertaking many trials, some generic central monitoring processes are contained in SOPs, rather than trial specific documents.

    Any relevant/important communication or contact relating to the conduct of the trial by the sponsor would be part of monitoring the trial and this oversight, be it telephone calls, emails or letters should be documented and musta be retained and this would also demonstrate regular contact with the investigator(s).

    There will be many documents received from the investigator sites as per the monitoring procedures, these could include: consent/eligibility documents, status reports (recruitment/withdrawals etc), self assessment questionnaires/checklists. The sponsor should ensure that processes are in place to ensure blinding of the trial is maintained if documentation that could potentially unblind the trial is to be handled in central monitoring activities, for example records sent from pharmacy. Any generated evidence that receipt and review of such information has taken place musta be retained and as such this could prevent the need to retain the actual copies of the documents received. Some non-commercial trials use a form of central monitoring that involves sending in information from the investigator site to a central data centre. It is important that if information that identifies a subject is sent, for example copy of consent form, for monitoring purposes, that the subject has given explicit consent for this and is aware of who will have access to their data and this process is recommended to be included in the protocol. A formal system should be in place at the receiving site to restrict access to confidential subject data with respect to compliance with the Data Protection Act. Compliance any local country-specific requirements will also be required.

    Additionally, the investigator site will submit the clinical data CRFs either using eCRF or faxing/sending paper CRFs. Any generated evidence of central monitoring activities regarding this data musta be retained, these could include reports generated from interrogating the database, for example, looking at data submission timeliness, audit trails of the eCRF to examine times of completion, data query rates and response timeliness, SAE reporting rate, comparisons/reconciliations with other databases (e.g. IVRS, Central Labs) and data from other sites. The investigator musta retain the original source document or a certified copy and the sponsor should not have exclusive control of a source document.

    The data validation activities, usually done by data management, would be expected to be documented and so musta be retained; this would include evidence of manual checks of CRFs and outputs of inconsistencies detected from data validation systems. It is recommended that the data validation activities are recommended to be focussed on the data that is critical to the reliability of the trial results as identified by the risk assessment rather than excessive resource spent on raising data queries whose resolution makes little or no impact on the quality of the trial, the safety of the subjects and reliability of the results. This is similar to the approach taken for proportionate source data verification (SDV) (see FAQ 26).

    There should be a formal process for dealing with issues and data queries identified during central monitoring and data management activities, including an escalation process. Any generated evidence of identification of the issue(s), review and discussion and subsequent actions musta be retained. The monitoring strategy and procedures mustb be followed and there should be documentary evidence of this.

    The use of central monitoring transfers some additional activities to the investigator site and may impact on site resources; however, the investigator and research team mustc conduct the trial in accordance with the principles of GCP and have some specific responsibilities they mustd undertake according to the legislation. Some of the additional activities needed for central monitoring may assist in ensuring that this occurs (e.g. completing a checklist for review of investigator site file contents).

    The MHRA is willing to publish examples here of central monitoring documentation (for example plans and output reports) to assist sponsors in developing processes and procedures. Sponsors, who wish to provide examples for consideration for publication, should contact the MHRA GCP Inspectorate: GCP.inspectors@mhra.gsi.gov.uk
    The examples are not intended to be definitive approaches. They are not endorsed or recommended by the MHRA.

    a. SI 2004/1031 (as amended) Regulation 31A (3)
    b. SI 2004/1031 (as amended) Regulation 28 (1) and (2), Schedule 1, Part 2, (4)
    c. SI 2004/1031 (as amended) Regulation 28 1(a)
    d. SI 2004/1031 (as amended) Regulations 12, 13, 14, 29 (a), 31 A (7) & (8) and 32

    Version 1: 22 February 2013
    Last edited by MHRA Super Moderator; 14th Nov 2014 at 11:04 AM.

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