FDA Issues Draft Guidance that Supports Developing a Risk-Based Approach to the Monitoring of Clinical Studies

By Anne Marie Murphy –

This week FDA announced the publication of a draft guidance titled, “Oversight of Clinical Investigations: A Risk Based Approach to Monitoring.”  This is the first time since 1988 that the agency issued a specific guidance document on how a study sponsor may meet its obligation to monitor or oversee the conduct of a clinical study. 

For purposes of the guidance, “monitoring” refers to the methods that sponsors and contract research organizations (“CROs”) use to oversee the conduct of and reporting of data from clinical studies.  FDA indicates that the primary focus of study monitoring should be protecting study subjects, ensuring the integrity of study data, and ensuring that clinical investigators comply with applicable regulations. 

Sponsors have always been free to adopt monitoring practices and procedures as they saw fit.  Historically, however, FDA notes that industry sponsors have relied heavily on frequent on-site visits to clinical sites to verify data and ensure compliance.  FDA also notes a misconception on the part of industry that FDA expects 100% verification of study data.  

In addition to on-site monitoring, the draft guidance encourages the use of centralized monitoring, i.e., remote evaluation of study data at a location other than the site where the study is being conducted.  The extent to which remote or centralized monitoring is used should depend on the complexity of the study and the electronic accessibility of study data.  According to the guidance, centralized monitoring should:

• include activities that can be done as well or better remotely (e.g., standard checks for consistency and completeness of data);
• target on-site monitoring by identifying higher risk clinical sites;
• perform monitoring activities that can only be done in a centralized manner (e.g., statistical analyses to identify data trends);
• identify missing or inconsistent data and potential protocol violations;
• verify source data remotely, where both source data and CRFs can be accessed remotely;
• analyze site characteristics (e.g., high screen failure or protocol violation rates and delays in reporting data);
• complete administrative tasks such as collecting regulatory documents.

For each clinical trial, FDA recommends that the sponsor develop a monitoring plan that describes:

• the monitoring approaches and procedures to be used;
• communicating monitoring results;
• managing noncompliance, including developing specific processes for investigating suspected data falsification;
• training and study-specific information, including training monitors and study site staff.

FDA intends to evaluate processes through which sponsors may voluntarily submit monitoring plans to the appropriate FDA review division and request feedback. 

The guidance also addresses a sponsor’s ability to transfer of monitoring obligations to a CRO.  It notes that any such transfer must be in writing, and that the sponsor retains responsibility to oversee the CRO’s activities. 

Comments on the draft guidance should be submitted by November 28, 2011.