FDA Strengthening Good Clinical Practice Oversight

Writing in an FDA Voices column, four senior agency executives describe ways in which FDA is strengthening its oversight of good clinical practice (GCP) as the ethical and scientific foundation for clinical investigations of all regulated products. The column was written by CDER acting director Michael Davis, CBER acting director Karim Mikhail, CDRH director Michelle Tarver, and Oncology Center of Excellence director R. Angelo de Claro.

The four say that GCP establishes a standard for the design, conduct, performance, monitoring, recording, analysis, and reporting of clinical trials in a way that helps ensure that the data and reported results are credible and accurate and that the rights, safety, and well-being of trial subjects are protected.

They report that the foundation of GCP is being tested by the scale and globalization of modern clinical research that is introducing new risks to oversight, transparency, and data integrity. “Multi-regional trials without an American patient at all or with only a small percentage of patients in the United States present a variety of concerns for American patients, for FDA, and, increasingly, for policymakers in Congress,” they write. “Trials that fail to enroll American patients can be less easily generalized to the population the products are intended to treat. It also means Americans are losing out on the opportunity to participate in trials of innovative or breakthrough medical products.”

The column says FDA is working to:

• expand inspection coverage at foreign clinical trial sites;
• improve communications with sponsors; and
• strengthen internal review training.

Steps the officials say the agency is taking as part of a renewed commitment to oversight and transparency are:

• increased transparency of inspection findings;
• heightened scrutiny of foreign data generated outside of an IND/IDE non-IND studies and sites; and
• active engagement at the pre-submission stage.

“What FDA is saying, plainly and with full intent to act on it, is that the standard is the standard,” the column concludes. “Geography does not change the evidentiary requirements. And it is incumbent on those sponsors coming to FDA to meet those requirements…. The message to sponsors is straightforward: plan your development programs to comply with all GCPs and proper human subject protection, in trial settings where FDA access will not be impeded from day one, and data integrity and informed consent are prioritized. If you are building a regulatory strategy around clinical data from sites where FDA has been unable to inspect, or from circumstances where the conditions for ethical research are in serious question, think again.”