The first change in ICH E6 – Guidelines for Good Clinical Practice is coming this year. We should remember that the previous version in the document history is dated June 1996. This time it is more prescriptive than previously and here is more emphasis around risk based monitoring and the use of centralized monitoring.
Central monitoring is clearly recommended as one of the appropriate methods to be employed in the monitoring plan. Central monitoring will become one of the key elements to continuous risk evaluation and reporting during the course of the clinical trial.
Even though central monitoring is considered a supplement to onsite monitoring activity, it is the core process that performs continual risk evaluation at the site level.
Central monitoring will require scheduled review of the critical data points as well as surveillance framework for any unknown or unidentified risks to be identified, evaluated and controlled as part of the risk based approach.
Here are the direct excerpts from the ICH E6 R2 draft which are worth noting from the central monitoring perspective.
Centralized monitoring is defined as a remote evaluation of ongoing and/or cumulative data collected from trial sites, in a timely manner. Centralized monitoring processes provide additional monitoring capabilities that can complement and reduce the extent and/or frequency of on-site monitoring by such methods as:
(a) Routine review of submitted data.
(b) Identification of missing data, inconsistent data, data outliers or unexpected lack of variability and protocol deviations that may be indicative of systematic or significant errors in data collection and reporting at a site or across sites, or may be indicative of potential data manipulation or data integrity problems.
(c) Using statistical analyses to identify data trends such as the range and consistency of data within and across sites.
(d) Analyzing site characteristics and performance metrics.
(e) Selection of sites and/or processes for targeted on-site monitoring
“Detection of deviations from the predefined quality tolerance limits should trigger an evaluation to determine if action is needed.”
“Outcomes of centralized monitoring should be reported”
The revisions to ICH E6 have been a long time coming, but they are sure to drive a paradigm shift in our oversight of clinical trials. The role of central monitoring as a tool to manage risk will be central to that movement.