NEW! FDA’s Guidance on Risk-Based Monitoring now Official

This month, FDA officially released the new Guidance for Industry: Oversight of Clinical Investigations – A Risk-Based Approach to Monitoring.  The draft guidance was originally released in August 2011, and has been a popular topic of conversation over the two year period before becoming final.  You may recall a recent blog we posted about the concept of Risk-Based Monitoring and how it seems to be met with some skepticism and confusion amongst the clinical research community.  Hopefully now, with FDA’s “current thinking” on the topic becoming official, we can all review what exactly FDA’s vision for the future of monitoring entails.

So what does FDA recommend for the current state of affairs when it comes to monitoring clinical research trials?  The guidance is basically the blueprint for the future of monitoring in the eyes of FDA.  Below are some key takeaways that stood out to us during review:

• FDA wants sponsors to use more modern, time efficient, combination methods to ensure compliance when conducting clinical trials, with an emphasis on centralized monitoring when possible.
• FDA is clear that they feel centralized monitoring for certain activities are not only adequate, but might be better than on-site monitoring due to advances in technology.
• Sponsors can meet and/or exceed statutory and regulatory requirements by using the risk-based approach.
• A risk-based monitoring approach does not mean less vigilant monitoring, it means more focused monitoring.
• FDA feels this not only applies to monitoring, but to clinical trial management as a whole.  They allude to future draft guidance expanding from monitoring to all aspects of clinical trial managment.
• FDA’s seriousness about this topic can be further evidenced by their communicating it to their staff in review, inspection, and compliance functions.
• There is published evidence to suggest that some activities such as fraud and other data anomalies can more readily be recognized from centralized monitoring approaches.
• FDA expects a decrease in on-site monitoring activities as more technological advancements occur in the near future.
• Centralized monitoring activities should guide the decision making process of when on-site visits may be needed, and on-site visits should not be done away with completely.
• There are some things that currently still cannot be done via centralized monitoring and therefore some level of on-site monitoring is still needed.
• Each clinical trial will be different and should have its own unique monitoring plan that has the most beneficial mix of monitoring techniques to ensure human subject protection and adequacy of trial data.
• Here are some examples of centralized monitoring activities that FDA encourages:
• Routinely review data submitted for inconsistencies, missing values, outliers, etc.
• Conduct statistical analyses at regular intervals that can identify trends not easily recognized.
• Analyze sites on key performance metrics that may signal poor performance.
• Verify critical data points remotely.
• Complete administrative and regulatory tasks. remotely/electronically.
• FDA specifically lists out what they consider critical data to be considered:
• Proper informed consent.
• Protocol eligibility criteria.
• Product accountability.
• Assessments related to study endpoints, patient safety measures, and adverse event reporting.
• Study conduct and procedures essential to trial integrity
• They also specify factors to consider when developing the monitoring plan:
• Complexity of the study.
• Types of endpoints.
• Complexity of the population.
• Geography.
• Experience of the clinical investigator.
• Whether or not EDC is used.
• Safety of the investigational product.
• Stage of the study.
• Quantity of data.

It’s our hope that summarizing FDA’s guidance will help quiet some of the noise surrounding the controversial topic of risk-based monitoring.  Change is often met with resistance, but we believe that through continued discussion and education all can see the benefits of this new mindset for monitoring clinical investigations.

Do you think the guidance will help clear up some of the controversy?  We would love to hear your thoughts on this guidance and the concept of risk-based monitoring as a whole.

Photo Credit:Patrick Haney