Clinical Events Committee

FDA Clinical Inspection Summary of Teva's Cinqair (reslizumab)

FDA did not post any warning letters to Sponsors/Monitors/CROs, IRBs or Clinical Investigators this week. From the archives, here is the clinical inspection summary for Cinqair (reslizumab) submitted by Teva. No sites were selected for inspection, as all study sites worldwide had very low enrollment. The sponsor, Teva, was inspected. No form 483 was issued; however the inspectors were instructed to look at four specific items during the sponsor inspection.

  • The inspection was directed to focus on the data fields that were changed post database lock. FDA also noted that the statistical analysis plan for the two studies was finalized after the first database lock, but before study unblinding. 
  • The inspection directed to investigate the process for adjudication of Clinical Events. FDA noted that the submitted eCRF data fields did not appear to be complete enough for proper adjudication.
  • Subjects who were excluded from the safety database were examined closely to determine the incidence of adverse events.
  • The inspection looked carefully at adverse events that FDA noted were of concern during the FDA's review of the submission. 

FDA Inspection Summary: Savaysa by Daiichi Sankyo

FDA did not post any warning letters to Sponsors/Monitors/CROs, IRBs or Clinical Investigators this week. From the archives, here is the Clinical Inspection Summary for Savaysa by Daiichi Sankyo. One thousand four hundred and twenty sites enrolled subjects over a course of five years. Sites with relatively high enrollment were chosen for inspection. Other factors for selecting sites for clinical inspection included  high favorable effect size, high or low rates of death/discontinuation, and low reported bleeding adverse events, a high ratio of NSAEs to SAEs, no events in the active arm, high numbers of adverse events. Five sites plus the sponsor were inspected. One site and the sponsor received 483s.

Dr. Salby received a 483 for failing to follow the investigational plan, specifically:

  • Three serious adverse events (SAEs) were reported to the sponsor late, ranging between 5 and 20 days late. 

The sponsor, Daiichi Sankyo, received a three item 483 for: 

  • Failing to ensure an investigation was conducted according to the investigational plan and protocol, specifically:
    •  The sponsor failed to follow the Clinical Events Committee (CEC) Charter, Data Monitoring Committee (DMC) Charter, and Academic Contract Research Organization (ACRO) agreement during the adjudication process. The CEC vendor did not retain all paper copies of adjudication forms.
    • The sponsor failed to ensure a CEC organizational meeting was held, as required by the protocol and CEC charter. 
    • Failing to have CEC members update their financial disclosure forms annually
  • Failing to notify the FDA when a site's participation was terminated due to noncompliance.
  • Failure to maintain accurate records of shipment, receipt and return of study drug.
    • Accurate quantities of drug returned from three study sites to depots was not recorded