The FDA issued guidelines on its acceptance of medical device clinical data from overseas studies in a just-issued draft guidance, saying the "increasing globalization of clinical trials presents challenges to both U.S. and foreign regulators."
The agency said the number of applications for clearance, approval or further clinical investigation based on foreign clinical trials has increased and will likely continue to do so. Challenges include "resource constraints that impact the number of foreign clinical sites" and the agency's desire to avoid unnecessary duplication of studies, the draft guidance says.
Under the Food and Drug Administration Safety and Innovation Act of 2012, the FDA is required to accept data from overseas trials to approve or clear a device as long as it was collected in conformance with good clinical practice, the Regulatory Affairs Professional Society points out.
The FDA acknowledges the law in the draft guidance and said it already accepted overseas clinical data in the first place. In addition, the guidance adds that overseas trials must be conducted in conformance with an international law known as the Declaration of Helsinki or the local country's requirements, whichever are more stringent.
If the laws of the local country are used, applicants must explain how they differ from the Declaration of Helsinki and why they offer greater protection to human subjects.
But mere acceptance of overseas clinical trial data is no guarantee of approval. The FDA says data collected overseas presents unique challenges and asks that differences in clinical conditions, study populations and regulatory requirements be taken into account in submissions.
"Differences in clinical facilities and levels of clinical skill can also affect OUS (outside the U.S.) study data to the extent that such data may not be generalized to US clinical practice and the differences could impact the data's usefulness in supporting the safety and/or effectiveness of the device," the FDA says.
The agency also says that providing subgroup analysis is particularly important when submitting data from overseas clinical trials because of the different characteristics of overseas populations compared to Americans, such as the foreigners' height, weight, possession of certain biomarkers like the BRCA cancer gene, and behavioral tendencies like smoking.
As is often the case, the guidance recommends reaching out to the agency early and often. "By seeking FDA feedback prior to initiating the OUS study, sponsors who intend to use an OUS study to support US clearance or approval, regardless of whether or not they intend to use that study to also support marketing authorization in another country, can help facilitate efficient clinical trial design and reduce the possibility that additional clinical studies may be needed to support marketing authorization in the US," the guidance says.
The draft guidance also encourages applicants to meet with the FDA if they intend to rely solely on foreign clinical data.
Examples of past experiences with overseas data provided in the draft guidance indicate that if the agency has concerns about the overseas clinical trial, it will sometimes accept a reanalysis of the foreign data. Other times, the overseas data can result in the company conducting a smaller clinical trial in the U.S. than would otherwise have been the case.
In the draft guidance, the agency said it is working on finalizing a more comprehensive proposed rule that would formalize the requirements of the Food and Drug Administration Safety and Innovation Act of 2012.
The draft guidance applies mainly to stringent PMA applications, but the proposed rule, "when finalized, would require that foreign clinical studies in support of PMAs, IDEs, HDEs and 510(k)s be conducted in accordance with good clinical practice (GCP)," the draft guidance says.
Since the recommendations are in the draft stage, the FDA is accepting comments on the document, which it will use to inform the final version of the guidance.