An Op-Ed by Dr. Nancy J Stark
FDA's draft guidance, "An Oversight of Clinical Investigations—A Risk-Based Approach to Monitoring" (August 2011) references the ICH-GCPs six times. The ICH-GCPs were written in 1996 by pharmaceutical sponsors and regulators from the US, Europe, and Japan. It is 15 years old and is showing a few signs of age—there is no discussion of central data management or electronic security issues, for example. But because the phrase 'good clinical practice' is in the public domain, ICH was free to adopt it as part of the title of document E6, "Good Clinical Practice: Consolidated Guidance." The Center for Drugs published the guidance in the Federal Register giving it high standing in the regulatory community.
Although used by device manufacturers, the guidance does not work well. It's description of an Investigator's Brochure is chemically-centered not mechanically-centered, investigational devices are stored and dispensed but never installed, there is no mention of training an investigator to use the investigational product, there is no mention of software-controlled devices or software collected data, no mention of caregiver or healthcare provider safety; in other words, for medical devices, the ICH-GCPs are inadequate and out-of-date.
ISO 14155 'Clinical investigation of medical devices in human subjects—Good clinical practice' (2011)—the internationally definitive document for medical device clinical studies—is not mentioned even once; yet the international standard was closely harmonized with ICH-GCP to promote international continuity. I could live with the lack of acknowledgement in FDA's guidance if the same FDA Office hadn't taken such a heavy hand in writing the ISO standard. It is wrong to insist on practice-changing language (such as moment of consent versus moment of enrollment) and then turn your back on the work product as FDA seems to have done.
The draft guidance draws heavily on the ever-increasing presence of electronic data collection. A really cool EDC system can spot a lot of site problems before the human eye ever gets to the data. But these systems are expensive (think in terms of a $1M for a modest study) and unaffordable to small start-ups.
Finally, it was the Offices of Compliance from CDRH, CDER, and CBER who wrote this guidance. While they promise us the inspection manual will be promptly updated to match the guidance, they do not make assurances that the reviewers in the Office of Device Evaluation will follow along. Sponsors are strongly urged to get buy-in on the monitoring plan from reviewers before initiating a clinical trial.
While device manufacturers can use the new guidance to their benefit, often to defend existing practices, they should make certain FDA's Office of Device Evaluation buys into any IDE monitoring plan.
Nancy J Stark, PhD
President, Clinical Device Group Inc