FDA WARNING_LETTER - University of Texas Health Science Center At San Antonio, The - December 06, 2024

The U.S. Food and Drug Administration (FDA) issued a Warning Letter to Dr. Ralph A. DeFronzo of the University of Texas Health Science Center at San Antonio following an inspection conducted from December 3 to December 6, 2024. The inspection, part of FDA’s Bioresearch Monitoring Program, identified significant deviations from regulatory requirements for clinical investigations. The primary violations concerned Dr. DeFronzo’s failure to ensure adherence to the investigational plan for Protocol (b)(4). Specifically, multiple subjects were enrolled despite not meeting critical eligibility criteria, including specified blood pressure and estimated glomerular filtration rate (eGFR) ranges, and the use of exclusionary medications such as SGLT2 inhibitors and GLP-1 receptor agonists. This raises concerns regarding subject safety and data integrity. Additionally, Dr. DeFronzo failed to promptly report substantial changes in research activity, specifically a modification in the study design for Protocol (b)(4) from a double-blind, placebo-controlled trial to a two-part study including a pilot feasibility phase, to the Institutional Review Board (IRB). These actions constitute non-adherence to the Federal Food, Drug, and Cosmetic Act and Title 21 of the Code of Federal Regulations, Part 312, which govern clinical investigations and human subject protection. Although Dr. DeFronzo responded by detailing protocol amendments and staff retraining, his response was deemed inadequate. The FDA noted that protocol changes were made well after subject enrollment and lacked sufficient detail on future oversight to prevent recurrence. The FDA mandates Dr. DeFronzo to ensure all studies are conducted according to the investigational plan to safeguard human subjects and maintain data reliability.