Risk-Based Monitoring Risky for Sponsors?

In August last year, the FDA came out with its Guidance for Industry Oversight of Clinical Investigations—a Risk-Based Approach to Monitoring. But why is it still garnering so much interest, almost one year later? Because sponsors and CROs alike are still examining the document and discussing how best to move forward. The FDA realizes there is hesitancy among the sponsor community, as it has outlined within the document.

In the guidance, which can be found at http://1.usa.gov/KlHybS, the FDA admits that the traditional on-site monitoring visit schedule of four to eight-week intervals, with 100% source data verification is based on industry's perception that is the FDA's "preferred way for sponsors to meet their monitoring obligations." The FDA further explains in the guidance that the previous 1988 guidance on monitoring of clinical investigations—which has been withdrawn—stated the "most effective way" to monitor an investigation was to "maintain personal contact between the monitor and the investigator throughout the investigation." But as the FDA points out, available means of communications between sites and sponsors was much more limited in 1988 than now. It says, there were only "limited ways to effect meaningful communication with investigators other than through on-site visits."

What the FDA Expects

The FDA offers in the guidance its thoughts on how sponsors should design their monitoring approach for a trial in a rational way. And to that end, it identifies the following nine key factors that sponsors should examine:

• Complexity of the study design

• Types of study endpoints

• Clinical complexity of the study population

• Geography

• Experience of the site staff

• Use of EDC

• Safety of the investigational product

• Stage of the study

• Quantity of data

The FDA also defines the steps it has taken or is taking to further the adoption of risk-based monitoring; and how to communicate the monitoring plan for the trial, and more. CROs, as usual, are not held accountable by the FDA in this document. The responsibility for oversight of the CROs work remains with the sponsor.

In the meantime, Ken Getz, Senior Research Fellow at Tufts CSDD, who wrote a background article on this topic in March 2011, http://bit.ly/MdQboz mentioned in another event that this move to risk-based monitoring could actually be used by CROs to lower their own operating costs. Specifically, CROs would be able to comply with the risk-based approach but provide fewer resources to the sponsor since 100% source data verification would no longer be necessary. "CRO's are always looking to improve their operating margins and this may afford some downsizing of study monitoring infrastructure. If a data collection risk is introduced that requires further investigation, I imagine that CROs will look to primarily use existing resources to perform that examination," said Getz.

Editor's Note: For a video blog on this topic, go to http://bit.ly/KRT5m2.