Background: Companion diagnostic (CDx) medical devices are essential in the development of precision medicine, providing information essential for the safe and effective use of a corresponding drug or biological product. CDx devices used during clinical trials generally need a distinct regulatory determination by regulatory authorities (either by IRB or FDA).
Methods: To identify companion diagnostics medical devices, all device Clinical trials received at an Independent IRB in January 2023 to June 2023 were reviewed from the database. Three sources of information were reviewed for companion diagnostic device determinations: 1. The device checklists (which reflect regulatory requirements outlined in 21CFR 812), 2. Documentation of device risk status provided by sponsor (rationale for NSR and/or FDA letter) and 3. minutes language. The CDx device determinations conducted by IRB or FDA were further analyzed. The device clinical trials were also classified as either oncology or non-oncology indications.
Results: During January to June 2023, our IRB reviewed 652 device clinical trials. During our evaluation of those protocols, we found that 47 (7.20%) involved the use of companion diagnostics devices. Out of those, IRB made 36 (76.6%) companion diagnostic device determinations with rationale submitted by the Sponsor. The FDA determined that 11 (23.4%) had companion diagnostics devices. Forty-two (89.4%) CDx devices were utilized in Oncology indications. Out of 42, 15 (36%) CDx devices were various FoundationOne CDx devices. Five (10.6%) CDx devices were also used in non-oncology indications such as hematology, genetics, hepatology, and cardiovascular disease. FDA made significant risk device findings for 3 (27%) companion diagnostics devices used in genetics, hepatology, and cardiovascular diseases. All oncology related indications companion diagnostics devices were non-significant risk devices as per the FDA. IRB review was a major factor in identifying and making regulatory decisions as non-significant risks CDx devices.
Limitations: We received certain device clinical trials that were utilizing companion diagnostic devices as exempt diagnostic devices in the study (i.e., used for exploratory or retrospective analysis). As the use of the devices in those situations was not as a companion diagnostics device, these clinical trials were not considered for analysis. Therefore, the proportion of reviews seen for those studies does not reflect the complete experience for using companion diagnostic devices.
Discussion: Our data show that the majority of CDx devices were used for Oncology indications. The use of CDx devices was intended to assist in patient identification and study enrollment. We also observed the use of CDx devices in non-oncology indications. Most of the CDx devices met the FDA requirements for non-significant risk (NSR) devices that were determined by IRB and some by FDA. Our analysis shows that our checklists, minutes, communication with sponsors re: NSR rationale, and regulatory documentation (FDA letters, etc.) have ensured that the IRB recognizes when a companion diagnostic device determination is required and documents it consistently.
