Decisions for Non-Significant Risk Device Studies: Laboratory-Developed Tests


Description of the Research

How should IRBs respond when a sponsor claims that Food and Drug Administration (FDA) enforcement discretion applies to its clinical investigation of a laboratory-developed test (LDT)? Responding appropriately is critical to maintaining compliance with FDA regulations. In this poster we highlight key aspects of FDA guidance and share information gained from communication with FDA regarding initial review of clinical investigations of LDTs.

In October 2014, the FDA issued draft guidance entitled "Framework for Regulatory Oversight of LDTs". This guidance outlines a proposed risk-based framework that refines an existing policy of enforcement discretion when an LDT – "an in vitro diagnostic  (IVD) that is intended for clinical use and designed, manufactured and used within a single laboratory" (p. 5) – is used in clinical treatment. 

Contrary to a sponsor’s claim that FDA enforcement discretion applied to its clinical investigation of an LDT, our correspondence with FDA and the FDA guidance explicitly indicated that FDA does enforce applicable regulations in such cases. Because LDTs are a type of IVD, IRBs must be able to assess whether a clinical investigation of an LDT is an investigational device exemption (IDE), meets abbreviated IDE and non-significant risk  device study requirements, or requires an IDE.

In determining whether the LDT might be IDE exempt, we revisited FDA guidance from June 2010 ("In Vitro Diagnostic [IVD] Devices Studies – Frequently Asked Questions"), which clarifies that IVDs are not exempt when their novelty means that there are no established products or procedures for confirming the diagnosis. 

Because the sponsor was actively marketing the device, it was felt that it would not meet the criteria for an abbreviated IDE. Therefore, we sought clarification from FDA regarding the applicability of the abbreviated IDE requirement to comply with "prohibitions in 812.7 against promotion and other practices" (812.29(b)(1)(vii)). In its response, the FDA indicated it would not require an IDE for a clinical investigation of an LDT solely because the sponsor had been marketing or promoting the device under the existing policy of enforcement discretion for clinical treatment. With this information, our convened IRB was able to consider whether the research represented a significant risk or non-significant risk device study as part of the criteria for an abbreviated IDE.

We are hopeful that other institutions will benefit from our communications with the FDA and be able to better identify cases in which an IDE is not required for a clinical investigation of a laboratory-developed test.