Anish S. Shah, M.D./Siyan Clinical Research – FDA Warning Letter, Dec 16, 2022

The FDA issued a Warning Letter to Dr. Shah following an inspection from December 5-16, 2022, regarding the clinical investigation of investigational drug (b)(4) (Protocol (b)(4)). The inspection, part of FDA’s Bioresearch Monitoring Program, identified a failure to conduct the investigation according to the investigational plan, specifically concerning blinding procedures [21 CFR 312.60].

Dr. Shah, as a designated blinded rater, conducted 16 Montgomery-Asberg Depression Rating Scale (MADRS) assessments for all three enrolled subjects. However, Dr. Shah was not blinded to certain safety assessments, including vital signs, clinical laboratory reports, and physical examinations for subjects (b)(6) and (b)(6). Dr. Shah acknowledged reviewing study records, consenting subjects, performing study-related assessments, and conducting the unblinded MADRS assessments. A protocol deviation was filed after realizing the error, and no further MADRS assessments were conducted by Dr. Shah.

While Dr. Shah's January 9, 2023, response detailed corrective actions, including identifying blinding requirements, consulting with the sponsor and a third-party quality group, and site personnel training (Good Clinical Practice), the FDA deemed the response inadequate. Insufficient details were provided on the implementation of proposed practices to ensure future compliance with blinding procedures. The FDA emphasized that the unblinded assessments raise significant concerns about the