The centralized monitoring report is the best channel to share risk signals with clinical trials stakeholders. In addition to being the perfect tool for the review of site-specific Key Risk Indicators (KRI) metrics with clinical operations teams, producing periodic reports ensures the traceability of the centralized monitoring activities for regulatory audit purpose. Reports are also essential for the continuous improvement of centralized monitoring processes.
The TransCelerate BioPharma Initiative specifically states that Monitoring reports should serve as tools for the team members to communicate a concise, high-level summary of monitoring activities, issues and associated actions. It’s imperative that companies build off of the knowledge they are gaining around RBM now to impact future use. TransCelerate also state that a risk-based monitoring (RBM) approach implies the ongoing adjustment of monitoring activities based on the issues and risks that may arise throughout the study.
As such, reports must include a concise evaluation of individual site-specific risk signals (i.e.: KRIs that fall beyond their set limits / thresholds) as well as a description of the actions performed to mitigate individual risk signals. If no action is performed, the report should still provide an analysis that justifies the fact that no action is performed in response to a given risk signal. Also, because KRIs limits / thresholds are likely to change when using an adaptive-type centralized monitoring approach, reports should document the adjustments made to KRI’s limits when they occur.
The FDA is relatively specific about what centralized monitoring reports should contain in their guidance A Risk-Based Approach To Monitoring of Clinical Investigations: Questions and Answers; Draft Guidance for Industry:
Question 8: How should centralized monitoring activities and the results of these activities be documented and shared with those involved in the investigation
Answer: As described in the RBM guidance, documentation of monitoring activities should generally include the following: (1) the date of the activity; (2) the individual(s) conducting and participating in the activity; (3) a summary of the data or activities reviewed; (4) a description of any noncompliance, potential noncompliance, data irregularities, or other deficiencies identified; and (5) a description of any actions taken, to be taken, or recommended (see section V of the RBM guidance for details). Such documentation should include the results of centralized monitoring activities in sufficient detail to allow verification of adherence to the monitoring plan describing those activities.
Reports of centralized monitoring activities should be provided to appropriate management, including sponsor staff responsible for investigation and site oversight, in a timely manner for review and follow up. In addition, sponsors should inform a CI of monitoring findings from centralized monitoring activities that are relevant to the CI’s activities.
It is therefore clear that producing periodic reports is essential for executing centralized monitoring. Considering the directives from TransCelerate and the FDA, the centralized monitoring report format displayed below can be used to effectively perform centralized monitoring.
A dashboard showing individual site-specific KRIs that fall beyond normal limits (yellow lights) and critical limits (red lights) provides a holistic view of current risks and makes for a neat cover page.
Limits / Thresholds
A limit section documents all current KRI limits / thresholds and the reasons for the changes made to them. See Setting Limits in Centralized Monitoring for more information on managing limits.
Individual Site-Specific KRI Evaluations
The individual site-specific risk signals and their variation can be presented along with their analyses and actions performed in a table format.
Using the RI Calculator, most of this information can be retrieved from the Calculator’s Metrics worksheet with one of the VBA macros available in the workbook. Namely, the identities of the site-specific KRI metrics which fall beyond their set limits / thresholds along with their variations can be transcribed automatically. Additional information including the KRI metrics evaluations and the actions taken can be manually entered on the report as part of the periodic KRI review. As described in the article A Centralized Monitoring Approach Using Excel for the Quality Management of Clinical Trials, the RI Calculator represents an effective solution for performing centralized monitoring and producing related reports.
Another VBA macro available with the RI Calculator allows gathering all the information mentioned above in a PDF document that can be distributed to all stakeholders through email or a shared directory. Maintaining a collection of the PDF reports serves to document the whole trial's Centralized Monitoring process. Indeed, if it's written, it happened.