FDA EIR - Hetherington, Dr Maxine - June 27, 2014

An FDA inspection of Dr. Maxine Hetherington, M.D., at Children's Mercy Hospital in Kansas City, MO, occurred from June 23-27, 2014. This was a High Priority CDER User Fee NDA Pre-Approval, Clinical Investigator Data Validation Inspection, conducted under Bioresearch Monitoring Compliance Program CP 7348.811, as part of a CDER-EMA collaborative initiative. The focus was on clinical protocols DIV-NB-301 and DIV-NB-302 concerning high-risk neuroblastoma. Key violations included the failure to conduct studies in accordance with the investigator statement. Specifically, there was delinquent reporting of Serious Adverse Events (SAEs) to the Institutional Review Board (IRB) and sponsor, and non-reporting of targeted toxicities and dose modifications. The facility lacked an adequate system for ensuring all study personnel were properly trained and aware of their protocol responsibilities, with incomplete or missing FDA Form 1572s for sub-investigators. Further issues comprised inadequate investigational drug accountability, inconsistent financial disclosures for physicians, improper waivers for subject enrollment, and inconsistent Adverse Event (AE) grading per NCI's CTCAE. The absence of regular sponsor monitoring and the site's failure to verify source data accuracy were also identified. Management acknowledged the deficiencies and indicated they would evaluate and implement corrective actions. A written response detailing these actions was required within 15 business days to the district and CDER.