When Is An Investigational Device Ready For Human Study? FDA Weighs In
FDA has finalized a guidance outlining risk-benefit factors manufacturers should consider when determining whether an investigational device is suitable for clinical study with human participants. A majority of the finalized guidance’s content is consistent with the draft guidance released in 2015, but additional sections clarify the FDA’s interpretation of a “well-designed study” and what effect study design has on the agency’s decision to approve an investigational device exception (IDE).
FDA acknowledges that evidence available for an IDE application may be significantly limited compared to marketing applications, and the degree of limitation depends on the device’s stage of development. Devices in early stages of development are typically associated with “greater uncertainty,” and the approval of an IDE will depend more on the manufacturer’s plan for risk mitigation.
The agency “believes that effective risk management, including the application of risk controls, which includes risk mitigation measures, can result in a favorable benefit-risk determination,” wrote regulators in the guidance.
The primary goals of the document — outlined in the introduction — are to clarify the agency’s approach to “anticipated risks” and “most probable risks,” characterize the agency’s understanding of benefit in the context of investigational research, and describe a variety of suggested risk-mitigation measures that an investigator or sponsor may want to implement.
A draft of the guidance was first published in June of 2015 and established a basic “benefit-risk framework” that the agency uses when making decisions. According to the Regulatory Affairs Professionals Society (RAPS), industry advocacy groups — including the Advanced Medical Technology Association (AdvaMed) — submitted comments on the draft, asking the agency to provide additional clarity.
Tara Federici, VP of technology and regulatory affairs at AdvaMed, submitted a letter to the agency asking FDA to clarify references to “well-designed” studies, pointing out that the subjective nature of the terminology may lead to inconsistent reviews. Also, Federici highlighted section 520(g) of the Food, Drug and Cosmetic Act amended in 2012 that prohibits rejection of an IDE application based on study plans.
In the finalized guidance, the agency clarifies that well-designed studies are “more likely to produce important knowledge about device or disease,” but that the agency would not disapprove an IDE based on the study plan alone. The guidance also specifies that the scope of the document refers to IDE applications, supplements, and amendments, while the draft referred more generally to IDEs.
FDA intends that the finalized guidance will improve the “predictability, consistency, and transparency” of its review process for IDEs, so that device investigators and sponsor-investigators can better anticipate the results of their applications.
“FDA believes use of this benefit-risk framework will facilitate the incorporation of evidence and knowledge from different domains—clinical, non-clinical, and patient—to support a comprehensive, balanced decision making approach,” wrote regulators.