Posted 21 April 2015
By Alexander Gaffney, RAC
New draft guidance issued by the US Food and Drug Administration (FDA) seeks to make it easier for medical device companies to rely on data obtained from clinical studies outside the US, provided those studies are conducted to appropriate federal standards.
The draft guidance document, Acceptance of Medical Device Clinical Data from Studies Conducted Outside the United States, is closely related to a rule proposed by FDA in February 2013. That rule, Human Subject Protection; Acceptance of Data from Clinical Studies for Medical Devices, proposed requiring all clinical studies conducted outside the US in support of a device application comply with US regulations on good clinical practice.
"The proposed rule is intended to update the standards for FDA acceptance of data from clinical studies conducted outside the US and to help ensure the protection of human subjects and the quality and integrity of data obtained from these studies," FDA wrote in the regulation.
The goal, regulators explained, was to promote consistency in the trials while assuring that human subjects participating in the trials were given adequate protections. FDA now accepts data from foreign-conducted clinical studies so long as they meet 21 CFR 812-14, which states that the obtained data must be scientifically valid and must have been collected per the ethical guidelines of the Declaration of Helsinki or local laws (whichever offers stronger protection to research subjects).
This data is most commonly used in support of an application that includes data from the US, but FDA encourages sponsors to meet with it if the application will be "based solely on foreign clinical data." Those requirements are less stringent than required for clinical trials conducted within the US, which are held to various US-specific regulations such as 21 CFR 56 (IRBs) and 21 CFR 50 (informed consent).
Read more about FDA's proposed rule here.
The change regulators need to account for, FDA explains in its newest draft guidance, is that medical device trials are becoming increasingly global.
"The number of IDE applications and submissions for marketing authorization supported by OUS clinical trials has increased in recent years and will likely continue to increase in the future," it wrote. "This increasing globalization of clinical trials presents challenges to both US and foreign regulators. Among the challenges are resource constraints that impact the number of foreign clinical site inspections and unnecessary duplication of clinical studies and administrative burdens."
Another change: Under Section 1123 the Food and Drug Administration Safety and Innovation Act (FDASIA) of 2012, FDA was required to accept data from clinical investigations conducted outside the US as long as the data were collected according to acceptable good clinical practices (GCPs).
While FDA said it had a "longstanding" approach to accepting this data, FDASIA served to codify the practice into law and called on FDA to clarify the processes by which the data could be accepted.
An Either/Or Approach
FDA's new practice, outlined in its guidance document, calls for an either/or approach.
Either a company's clinical trials conducted outside the US exactly meet federal human subject protection requirements, or they meet local standards, which a company must show are either equal to or greater than US requirements for human protection under the 1983 version of the Declaration of Helsinki.
In addition, FDA's guidance addressed what it calls "valid scientific evidence"—evidence from what FDA defines as "well-controlled investigations, partially controlled studies, studies and objective trials without matched controls, well-documents case histories conducted by qualified experts and reports of significant human experience with a marketed device."
"Should FDA determine that the OUS data constitute valid scientific evidence, under 21 CFR 860.7, then the OUS data can be used to support clearance or approval of the application," FDA wrote. Sponsors intending to rely on outside-the-US (OUS) data should "seek input from the relevant … review division at the earliest stage possible using the Pre-Submission process," it added.
Which factors should sponsors take into account when assessing whether they can rely on OUS data? FDA says sponsors should take into account three main questions:
- Are there differences in clinical conditions which might affect the standard of care afforded to a patient?
- Are there differences in the populations being studied, which might preclude the data from being extrapolated to US patients?
- Are there differences in regulatory requirements which might cause the study to fail to meet US requirements?
FDA is accepting comments on its guidance until 20 July 2015. The draft guidance also notes FDA is continuing work on its proposed rule, Human Subject Protection; Acceptance of Data from Clinical Studies for Medical Devices.
Acceptance of Medical Device Clinical Data from Studies Conducted Outside the United States (FR)