Approximately a third of clinical trials conducted utilize some elements of Risk Based Monitoring (RBM), with this figure expected to increase. Site monitoring has been identified as one of the largest components of clinical trial expenditure. With the change in the way that site monitoring is performed, the role of the Clinical Research Associate (CRA) is significantly changing.
With RBM, on-site visits would be triggered based on pre-determined risk factors, as opposed to pre-determined intervals. In order to interpret changes in these risk factors at site level, CRAs need to have a much deeper understanding of their trial, their sites and their patients than before. CRAs remain the key link between the clinical team and the site, and should be included in central team discussions and decision making regarding risk analysis of the site. In order to better support sites remotely, CRAs also increasingly perform cross functional coordination and direct communication with vendors. Traditionally, the Project Manager plays the central cross function coordinator, however adoption of some of these activities by the CRA in the issue-escalation and communication plan becomes beneficial.
This shift in focus to risk identification means that the role of the CRA has become a blended ‘compliance’ and ‘risk assessor’ role. This article seeks to explore this change from three aspects, namely site interaction, CRA oversight and change management.
Interaction with sites
The decrease in on-site visits associated with an increase in remote communication with site personnel through the systems employed results in less face to face interaction as the average number of on-site visit falls.
Feedback suggests that this shift places an increasing demand on site personnel. With the decreasing number of on-site visits, CRAs have become less self-sufficient when it comes to access of on-site documents. Hence, there is more onus placed on site personnel, as they have to spend more time communicating with CRAs and updating systems. The perception amongst ex-study coordinators is that there is an increased responsibility for coordinators to ensure protocol compliance and collection of trial data. Traditionally, the CRAs provide a lot of support to site staff for these activities – but as their role shifts to a risk assessment role, study coordinators also have to shift their responsibilities in parallel.
CRAs have to manage this increasingly virtual relationship with site, and possibly deal with more complex issues through this type of relationship. This places a demand for a different set of communication skills from the CRAs.
A greater number of systems are utilized to enable RBM implementation, such as CL, IXRS, eCRF, CTMS and eTMF. There are now a large number of reports that readily provide objective measures of performance. For example, metrics reports such as queries, missing visits, open issues, missing pages, Investigator File completeness, monitoring visit report completion metrics, outstanding SAEs/endpoints, are all now instantly available. CRAs performance are now instantly quantifiable and afford greater transparency.
However, this large amount of readily available data is not always utilized to its full potential. In the sponsor/CRO scenario, risk assessments and decision making may sometimes be held solely with the sponsor. As the CRO is responsible for CRA oversight, it is beneficial to form strategic partnerships between sponsors and CROs so that risk analysis is always shared and the CROs and their CRAs can respond more intelligently.
This drift in CRA focus and responsibilities is well recognized. Some organizations have created specialised CRA roles that are distinct from the ‘traditional’ CRA role. However, for mid-sized or smaller organizations, CRAs must adapt and grow accordingly. Change management should therefore be at the forefront of effective application of RBM model.
To facilitate this change, there are several ways to support CRAs with this shift. Training that CRAs receive should be targeted towards a comprehensive understanding of the trial, systems, communication skills, risk and management plans. In particular, targeted training sessions on risk management strategies and decision making are particularly important as this is not typically part of CRA training traditionally. CRAs have the closest knowledge of sites and their knowledge should be used in assessing and adapting monitoring plans, which are essential for successful RBM implementation.
Managers should also provide more autonomy to the CRA level with RBM, as they should be part of the feedback loop for risk identification, assessment and decision making. For example, instead of assigning CRAs targeted visit schedules based on risk data, CRAs should be involved in the risk assessment of the site throughout the study lifecycle. Without this feedback loop, true RBM cannot be realized.