The role of the central monitor
On the 17th November 2016, the ICH Assembly reported that they had adopted the important amendment, ICH E6 (R2) that aims to encourage sponsor to implement improved oversight and management of clinical trials and that the amendment would now be implemented by ICH members through national and regional guidance. (http://www.ich.org/ichnews/press-releases/view/article/ich-assembly-osaka-japan-november-2016.html).
While we wait to see what implementation timelines will be adopted by the main regulatory authorities, I’d like to examine what impact the revision is likely to have on critical roles and responsibilities within our organizations, specifically on the role of the central monitor.
In a recent blog, I wrote that there is a temptation to make E6 (R2) a bigger organizational change than it needs to be, and that keeping it simple was the best approach. The intent behind the revision could achieved by simple process changes, clear expectations on standard practices, tools to facilitate process change, and education on why we are changing how we do things. That we don’t need to do it all at once and organizational roles, functions, processes and technology can and will evolve as we gain in experience.
While I stand by those statements, I firmly believe that new roles will emerge in this new world of improved quality oversight. One of the roles that is likely to emerge quickly, in fact in a number of organizations we are seeing this role and function take shape, is that of the Central Monitor.
I recognize and often advise that the implementation of a central monitoring function or role may not be practical or suited to many organizations at this time, for many and varied reasons, but the purpose and intent of a central monitoring role should be considered as part of the E6 (R2) implementation, even in the simple and pragmatic approach. The central monitor is likely to be a critical success factor in realising the full benefits of ICH E6 (R2) and releasing operational capability in adaptive monitoring practices.
Below is an outline job description for the Central Monitoring Role, defining some of the key functions this role should be responsible for:
The key functions performed by a Central Monitor will include, but may not be limited to the following areas:
During study planning and start up:
- Support the study management team by contributing to the identification of protocol critical data and processes
- Support the study management team by contributing to the protocol risk assessment
- Support the study management team by contributing to the (data) monitoring plan
- Support the bioinformatics and clinical systems team by contributing to the design of protocol and site risk indicators (KRIs) and other detection methods
- Preparation and review of the study central monitoring plan
During study conduct:
- Conduct periodic reviews of aggregate clinical trial data, as described in the central monitoring plan, to include, but not limited to, data listings, key risk indicators
- Use listings and aggregate data review tools to identify investigational sites that are displaying higher risk behavior and or data
- Conduct root cause analysis on the risk signals, using available data e.g. listings, remote monitoring of eCRFs, KRI source data, this may require interaction with other functions e.g. clinical monitoring, data management, biostatistics
- Provide direction to site monitors for additional remote and on-site monitoring activities for risk sites, within the scope of the trial monitoring and central monitoring plans
- Conduct periodic review, as described in the central monitoring plan, of aggregate data for trends within a site to further support RCA and direct monitoring activities
- Review the effectiveness of the recommended actions and take appropriate additional actions if no effect is observed
- Provide periodic risk profile reports, as described in the central monitoring plan, to the site and remote monitors, for all investigational sites
- Conduct periodic review, as per the central monitoring plan, of aggregate data for trend across sites within a country, across sites within a study, sites across studies to contribute to the continuous risk assessment process
- Notify the study management team if any new risks are emerging
- Support study management team in risk review and management activities
Must have worked as a clinical research practitioner for a minimum of 3yrs in an operational function e.g. data management, clinical monitoring, medical monitoring
Must have a proven track record of successful delivery, including effective management and understanding of data, and accountability for quality and timelines.
- Must be able to communicate clearly and effectively at all levels in an organisation and with external customers.
- Must be able to manage time effectively, working with multiple functions and requirements
- Must have been involved in the use of trial management or data management systems
- Must have been involved in the analysis and review of clinical data
- Must be skilled at problem definition and hypothesis testing
- Must be very IT literate
- Must be a fast learner and able to understand new concepts quickly
- Ideally a basic level of understanding of descriptive analysis e.g. means, medians, significance, confidence intervals