FDA EIR - Charles J. Coté, MD - April 30, 2008

The FDA conducted a high-priority clinical investigator inspection of Dr. Charles J. Coté, MD, at Massachusetts General Hospital, from April 14 to April 30, 2008. This inspection, carried out under the Center for Drug Evaluation and Research's Good Clinical Practice program (Compliance Program 7348.811), focused on studies involving the drug Zemuron® (rocuronium bromide) for an NDA pre-approval. The inspection identified four significant observations. These included a failure to maintain accurate and adequate patient records, specifically concerning missing or inaccurate drug administration data (infusion rates, total doses, and drug concentrations), and a lack of documentation for study drug preparation and administration. There were also concerns about unlisted study personnel and instances of falsified signatures on regulatory documents and patient assent forms. A major issue involved improperly documented informed consent, with evidence of missing signatures and dates from subjects or their legal representatives, and blood samples collected without proper consent. Furthermore, informed consent was not provided in a language understandable to all participants' representatives. Lastly, study drug administration occurred without documented direct supervision by the clinical investigator or subinvestigator for two subjects. Dr. Coté acknowledged the observations as "very fair" and committed to providing a written response to the FDA within 30 days. The sponsor, Organon, indicated plans to review the clinical trial data from the Massachusetts General Hospital site, as well as other research locations, by unlocking the database. This inspection will be reviewed by CDER for final classification.