FDA WARNING_LETTER - Ralph A DeFronzo, MD - December 06, 2024

The U.S. Food and Drug Administration (FDA) issued a Warning Letter to Dr. Ralph A. DeFronzo following an inspection of his clinical site conducted from December 3 to December 6, 2024. The inspection, part of the Bioresearch Monitoring Program, identified significant deviations from regulatory requirements under the Federal Food, Drug, and Cosmetic Act and 21 CFR Part 312, which govern clinical investigations and human subject protection. The primary issues observed involved Dr. DeFronzo"s failure to conduct clinical investigations according to the approved investigational plan. Specifically, multiple subjects were enrolled in a study despite not meeting critical eligibility criteria, including specific blood pressure and kidney function ranges, and the use of exclusionary medications. These lapses raised serious concerns about the safety and welfare of enrolled participants and the reliability of study data. Furthermore, Dr. DeFronzo failed to promptly report significant changes in research activity, such as a major modification to a study"s design from a double-blind, placebo-controlled trial to a two-part study, to the Institutional Review Board (IRB). Although Dr. DeFronzo submitted a response detailing protocol modifications, staff retraining, and new internal checks, the FDA deemed it inadequate. The agency noted that the protocol changes occurred long after subject enrollment, and the response lacked sufficient detail on how Dr. DeFronzo would ensure robust oversight of study procedures and prevent similar violations in the future. The FDA requires comprehensive corrective actions to address these serious deficiencies.