Ex-FDAer Unger Explains ‘FDA Medical Queries’
FDA is likely to expand its use of new FDA Medical Queries (FMQs ) on many NDAs and BLAs during their safety reviews, and incorporating the results in labeling, according to former CDER Office of Cardiology, Hematology, Endocrinology, and Nephrology director Ellis Unger, who earlier this year joined Hyman, Phelps & McNamara (HPM) as a principal drug regulatory expert. Writing in a 9/23 post on the law firm’s FDALawBlog site, Unger explained how FMQs work and predicted the agency will not initially mandate sponsors conduct these, but they are likely to be adopted by many firms. “Running FMQs on clinical datasets prior to, or during, NDA review could shed important light on FDA’s safety concerns and may become an industry best practice. Because we believe such information is highly important, HPM has developed the capacity to run the FMQs for our clients with a rapid turn-around time.”
The increased interest in FMQs was presented by FDA officials during a 9/14 FDA and Duke-Margolis Center for Health Policy virtual meeting on advancing premarket safety analytics, where Unger also participated on a stakeholder panel. His online post explained how for several years FDA has been including groups of related preferred terms in tables in the Adverse Reactions Section of drug labeling (Section 6), “generally describing such groupings with the use of footnotes. For example, Table 20 in Section 6 of the current Latuda labeling includes the term ‘somnolence’ with the footnote ‘Somnolence includes adverse event terms: hypersomnia, hypersomnolence, sedation, and somnolence.’ Such groupings have generally seemed to appear in labeling on an ad hoc basis, without standardization.”
The post also included an FDA-shared example of how the use of queries can lead to a more accurate characterization of adverse drug reactions. “In this example, only adverse events with a frequency greater than 2% in the drug group were to be included as adverse drug reactions,” Unger wrote. “When assessing anxiety as a single preferred term, the frequency in the drug group was slightly less than 2%; therefore, anxiety was not classified as an adverse drug reaction. When related preferred terms were included in an anxiety query, e.g., ‘nervousness,’ ‘general anxiety disorder,’ the frequency exceeded 2% and was included as an adverse reaction in the drug labeling. This example represents a situation where the existence of the adverse drug reaction depends on whether it is based on a single preferred term (‘anxiety’), or a grouping of anxiety-related preferred terms.”
During the virtual meeting, FDA also shared its new “Standard Safety Tables and Figures: Integrated Guide,” and included presentations on “standard safety tables and figures, tabulation of adverse events, statistical considerations in the analyses of adverse events, discussion of relative risk vs. risk differences, and advice on pooling trials (including Simpson’s Paradox), ascertainment windows, standard laboratory analyses, and drug-induced liver injury,” according to Unger.
A replay of the meeting can be watched here.