Good Clinical Practice Guide
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Thread: MHRA produced FAQs for Risk Adaptive Approach

  1. #11
    10. Can the risk assessment be amended?

    Yes. In fact it would be expected that the sponsor undertakes a continual review of the risk assessment, which is particularly important when new information becomes available. For example, the risk assessment should be re-examined following a protocol amendment or when new data is obtained (new SmPC, related pre-clinical/clinical trial results are released, a data monitoring committee meeting or interim analysis takes place). If the risk assessment is reviewed and it is not updated, the sponsor should document that the review has taken place. It is important when applying a quality risk management process that systems are in place for identification of new or unanticipated risks and taking appropriate actions. For example, a serious breach may occur and this may result in an amendment to the risk assessment with additional, changed or new mitigating actions required, such as changes to the type and/or frequency of monitoring.
    Version 1: 01 March 2012

  2. #12
    11. Will MHRA GCP Inspectors want to see the risk assessment at a GCP inspection?

    Yes, where applicable (i.e. risk adaptive approach is being used). As a key document for defining the management activities for the trials, GCP inspectors will review this and the supporting process in some detail. The risk assessment, where it is documented well, will provide the rationale behind trial management/monitoring and GCP activities applied, or not, to the trial. For example, as described in the safety management or monitoring plans and also the resultant documentation that is available for reconstructing the trial conduct that is filed in the Trial Master File.
    Version 1: 01 March 2012

  3. #13
    12. Is the safety monitoring plan (suggested to be submitted as part of the CTA) part of the risk assessment?

    Yes. The safety monitoring plan is the product of undertaking the risk assessment primarily concerning the risks of the IMP(s), as outlined in section A of the Appendix 2 of the risk-adaptive approach. As such, this would be part of the overall risk assessment and the information required to be submitted is a subset of the risk assessment process. The sponsor is encouraged to document the risk assessment such that it facilitates the extraction of this information ready for submission as the safety monitoring plan in the CTA (as a separate document, in the protocol or in the covering letter).
    Version 1: 01 March 2012

  4. #14
    13. Should the risk assessment consider investigator site staff experience and training in clinical trials/GCP etc.?

    Whilst the aspects for consideration in this area were not addressed in the risk-adapted approach*, this area is also a crucial aspect of the risk assessment process and must also be considered. This is recommended not only to be undertaken at a generic level, considering the risk and mitigations that are required across the trial for all sites, for example processes for initiation, but also at a site-specific level; looking specifically at the information gained about the site during an appropriate suitability assessment (e.g. questionnaire return, audit or pre-selection visit). This would then focus on any site-specific mitigations (e.g. additional training for site staff, additional oversight/monitoring) that may be required to be put in place or conversely, if the site is well known to the sponsor from previous experience and this has been documented; this may lead to a reduction in required oversight activities. A site?s facilities and personnel resources may change over time and this may impact on the site specific aspects of the risk assessment and thus be important in the ongoing review.

    * http://www.mhra.gov.uk/home/groups/l.../con111784.pdf
    Version 1: 01 March 2012

  5. #15
    14. Who should review the risk assessment?

    A multidisciplinary team, as described above is expected to conduct the risk assessment. It is up to the sponsor to decide if any additional review is required, this could be by senior management, other project teams/key individuals or could be in the form of an independent peer review. The MHRA would recommend that the need for or type of review is proportionate to the risks identified in the trial.
    Version 1: 1st March 2012

  6. #16
    15. Is it necessary to submit the risk assessment to the MHRA and the REC?

    No, this is not required and there are no current plans for this to change. The MHRA do want to see the safety monitoring plan for trials under the notification scheme, which, as described above, is part of the overall risk assessment. It should be noted that information contained in the risk assessment may prove useful in completing the application form for approvals, particularly for the REC application.
    Version 1: 01 March 2012

  7. #17
    16. The guidance suggests that the CI/sponsor?s assessment of the IMP risk category is included in the CTA application and gives an example of how this could be presented. Would the GCP Inspectorate consider this level of detail to be sufficient as an assessment of the IMP risk category (within a wider risk assessment of the trial) for the TMF?

    Yes, there should be a rationale for the trial type (A, B or C) as part of the risk assessment. The example table in the risk-adapted approach* is suitable to document this. A full bespoke risk assessment is also required.
    * http://www.mhra.gov.uk/home/groups/l.../con111784.pdf
    Version 1: 01 March 2012

  8. #18
    17. Can the risk assessment be discussed with the MHRA prior to submission of the CTA?

    A risk assessment based on the potential risks associated with the use of the IMP should be made by the sponsor. Background documentation on how to do this is provided on the MHRA website. The MHRA does not normally advise on the IMP risk stratification or on the eligibility of individual clinical trials for the notification scheme prior to an application being made by a sponsor. Example risk assessments will be reviewed by the MHRA GCP Inspectorate and published on the GCP Forum to assist sponsors in developing their risk assessment processes.
    Version 1: 01 March 2012

  9. #19
    18. Won?t the risk assessment process increase the paperwork required for a clinical trial?

    Whilst undertaking the risk assessment is an additional activity, its benefits in terms of application of risk-adaptive approaches are likely to be much greater than the impact of undertaking it. For example subsequent activities and documentation requirements may be reduced as a result. It is probable that sponsors are already undertaking such a risk analysis anyway and it needs to be formalised in procedures. Additionally, the risk assessment will allow a more detailed assessment of necessary management, monitoring and governance arrangements needed for the trial and this would be beneficial in improving the quality of the trial and the safety of clinical trial subjects.
    Version 1: 01 March 2012

  10. #20
    19. Does the risk assessment need to be global or country specific?

    For multi-country trials, a global risk assessment for the trial is acceptable, but part of the risk assessment areas would be to assess any country-specific risks ? for example differences in clinical practice, local regulations etc.
    Version 1: 01 March 2012
    Last edited by MHRA Super Moderator; 29th Mar 2012 at 05:18 PM.

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