The U.S. FDA is advising devicemakers that plan to use data from clinical studies conducted outside the U.S. to support an FDA premarket submission to meet with the agency before finalizing their trial design.
Meeting with the FDA early in the trial design process can help manufacturers ensure that the FDA will accept their OUS study data as valid scientific evidence, a issued Wednesday states. Otherwise, the agency may request additional or duplicative U.S. trials.
While the agency has long accepted such data, provided it conforms to national and international laws governing clinical trials, a growing trend toward conducting device trials outside the U.S. has created the need for clearer guidance on FDA policies toward use of overseas studies. A separate rule is being finalized that will require overseas trials to be conducted according to good clinical practices, the draft notes.
Trial models that meet the FDA’s standards for valid scientific evidence include well-controlled investigations, partially controlled studies, objective trials without matched controls, well-documented case histories and reports of significant human experience with a device, the agency says.
Devicemakers should consider whether the clinical conditions in the country where the trial is being conducted — such as standard of care — match those in the U.S., to enable the FDA to more accurately look at benefits and risks. Level of clinical skill among caregivers may also make a difference, the guidance says.
Sponsors should try to recruit study populations that match the U.S. patient population in areas such as race, gender, ethnicity and age.
Other variables that may need to be considered include prevalence of smoking, diabetes and obesity, and cultural or language differences that may affect the interpretation of study results.
If differences exist between the OUS study subjects and the intended U.S. patient population, sponsors should either find a way to mitigate those differences or explain why they believe they don’t affect the device’s safety and effectiveness, the FDA says.
Sponsors should also consider the possibility that FDA requirements will differ from those where the OUS trial is conducted — for example, a foreign regulator may require proof of safety and performance, while the FDA standard is safety and effectiveness.
The draft guidance includes examples of seven cases where OUS data was used to support a device application and why the agency accepted or rejected its use.