On August 29, 2011, the Food and Drug Administration (FDA) released draft guidance entitled “Oversight of Clinical Investigations: A Risk-Based Approach to Monitoring,” which can be found here.1 The FDA has not released a similar guidance for more than 23 years. There is a 90-day comment period during which members of industry, professional organizations and the public can submit written comments to the agency for review and consideration.

The guidance is intended to assist sponsors of clinical investigations with clinical trials relating to human drugs, biologics, and medical devices. Although the overriding theme of the guidance is the protection of human subjects, the FDA is clear that onsite visits are not always necessary and that “centralized monitoring” may be the preferred method for clinical trial monitoring. Centralized monitoring is a remote evaluation carried out by sponsor personnel or representatives, or clinical monitors at a location other than the sites at which the clinical investigation is being conducted.  

However, the FDA is not discouraging onsite visits when a protocol is complex or the subject population carries a high rate of co-morbidity. Through the guidance, the FDA encourages a risk-based approach when looking to fulfill sponsor monitoring duties. This means there may be some instances when onsite monitoring is most appropriate. One size does not fit all, but the FDA is adamant in having sponsors consider centralized monitoring.  

Guidelines to follow in choosing an approach have to do with the resources, training, safeguards in place, the experience of the investigator, as well as the severity of illness experienced by the study population. The guidance lists several factors to consider when developing any type of monitoring plan:

  • Complexity of study design
  • Types of study endpoints
  • Clinical complexity of study population
  • Geography
  • Relative experience of the clinical investigator and of the sponsor with the investigator
  • Electronic data capture
  • Relative safety of the investigational product
  • Stage of the study
  • Quantity of data

One obvious advantage to offsite or centralized monitoring is the potential time and money saved. It is less time-consuming and human intensive to gather and study data remotely. In addition, it will allow the more efficient sharing of data with investigators and the FDA. It could even be postulated that centralized clinical trial monitoring could speed up drug development times. In the guidance, the FDA clearly expresses that onsite monitoring takes place more than is necessary, and that centralized monitoring should be placed in the risk assessment mix.  

Centralized monitoring may be disruptive to some sponsors who maintain organizations and cultures conducive to on-site monitoring. It would seem to follow that those sponsors who can adjust to centralized monitoring stand a better chance of working more smoothly with the FDA, as well as possibly expediting the approval of their products.  

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