FDA Updates Current Thinking on Risk-Based Monitoring

SPOTLIGHT EVENTRisk-Based Monitoring – Beyond Theory In-Depth ReviewMarch 13, 2014
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I’m spending some time going through the Draft Guidance for Industry Oversight—A Risk-Based Approach to Monitoring, August 2011 vs. the Guidance for Industry—Oversight of Clinical Investigations—A Risk-Based Approach to Monitoring, August 2013, released yesterday in fact, and alerted to me by a Tweet by Alexander Gaffney, the Regulatory Focus News Editor for RAPS.

Gaffney also graciously shared that the FDA has a habit of replacing the Guidances with the same URL on their web site, so in this case, my saved URLs for the 2011 document all link to the updated 2013, making my desire to compare them an initial challenge. But with persistence and Gaffney’s advice, I found the Draft here.

And really, there is a lot to compare. Through the commenting period, clearly the FDA was able to flesh out, reference, and “recommend a quality risk management approach to clinical trials” more fully.

As Gaffney noted in his news update the Guidance references centralized monitoring methods more thoroughly. In the Background section, the FDA specifically discusses changes in the industry related to the increasing use of electronic systems and records and improvements in statistical assessments, “present opportunities for alternative monitoring approaches (e.g., centralized monitoring) that can improve the quality and efficiency of sponsor oversight of clinical investigations. FDA encourages sponsors to develop monitoring plans that manage important risks to human subjects and data quality and address the challenges of oversight in part by taking advantage of the innovations in modern clinical trials.”

Interestingly, this sentence in the updated Guidance references an article from 2012 about statistical approaches to central monitoring can “help improve the effectiveness of on-site monitoring by prioritizing site visits and by guiding site visits with central statistical data checks,” an approach that is supported by illustrative examples using actual trial datasets. Further down, the FDA strengthens its support of technological advancements by stating the increasing use of EDC and electronic systems in records facilitates remote access, therefore, a decreased use of on-site monitoring will evolve.

I’ve heard from speaking to people in risk-based monitoring that sponsors are still a little wary of the change to monitoring, and CRAs may be a little more than skeptical of the need for change. In the Draft guidance, the FDA took some responsibility for the industry’s interpretation and use of 100% Source Document Verification and its ancillary use of on-site monitoring on a strict 4-to-8 week basis. No longer. The FDA references a review that says, “The review determined that centralized monitoring activities could have identified more than 90% of the findings identified during on-site monitoring visits.”

Maybe 100% SDV and on-site monitoring is easier. A risk-based approach to monitoring as outlined by the FDA, and others such as TransCelerate BioPharma’s Risk-Based Monitoring Methodology Paper is more amorphous, study-specific and maybe considered more work in the start-up phase. But FDA is looking to technology to provide that help.

For CRAs or others who are skeptical, the FDA is not suggesting that oversight stop. It clearly states: A risk-based approach to monitoring does not suggest any less vigilance in oversight of clinical investigations. Rather, it focuses sponsor oversight activities on preventing or mitigating important and likely risks to data quality and to processes critical to human subject protection and trial integrity.”

For more articles on Risk-Based Monitoring, and interviews with those who provide technology and services in this space, please visit www.appliedclinicaltrialsonline.com/rbm