In industry, the current monitoring practice relies on ‘on-site monitoring’ and 100% source data verification (on all data fields). This process is very costly and is one of the main reasons that the clinical trials now become so expensive. This process is really the most conservative interpretation of ICH E-6 guidance on
Guideline for Good Clinical Practice and the 1988 FDA’s “Guidance for the Monitoring of Clinical Investigations”. These guidance only require “the sponsor should ensure that the trials are adequately monitored” and leave the door open in terms of the frequency of the monitoring and the approaches of the clinical monitoring. In industry, the conduct of the clinical trials are highly regulated. Sponsors are usually take the most conservative approaches no matter how costly these approaches are.
Will ‘on-site monitoring’ be really effective? Will 100% source data verification really be needed? Should we identify the new ways to conduct the cost-effective clinical monitoring?
Last month, FDA withdrew its 1988 guidance on “Guidance for the Monitoring of Clinical Investigations” and issued its draft guidance “Oversight of Clinical Investigations - A Risk-based Approach to Monitoring”. The newly issued guidance suggested it is acceptable to use alternative approaches (such as remote monitoring, centralized monitoring, risk-based monitoring). The guidance also suggested that the source data verification should be focused on critical fields (key efficacy and safety variables) and less than 100% source data verification on less important fields may be acceptable. The guidance gives a clear signal that the Sponsors are encouraged to explore the cost-effective ways to conduct the clinical monitoring instead of solely relying on the on-site monitoring.
If this guidance gets implemented, we may expect the increasing role of statisticians in clinical monitoring, especially the centralized monitoring. Currently, statisticians will identify the issues in the late stage of the clinical trials when statisticians or statistical programmers start to perform the data analyses. The new guidance says:
“…notably, the advancement in EDC systems enabling centralized access to both trial and source data and the growing appreciation of the ability of statistical assessments to identify clinical sites that require additional training and/or monitoring.”
“Centralized monitoring is a remote evaluation carried out by sponsor personnel or representatives (e.g., data management personnel, statisticians, or clinical monitors) at a location other than the site(s) at which the clinical investigation is being conducted.”