The US Food and Drug Administration (FDA) this week sent a Warning Letter to a Principal Investigator for allegedly failing to adhere to the agreed-upon investigational plan, among other alleged deviations.

The letter, made public by FDA on 28 May 2013, pertains to observations made by regulators during a series of inspections conducted in late 2012 of a clinical site maintained by Dr. Jose Joseph-Vempilly, a Fresno, CA-based investigator. Those investigations resulted in a FDA Form 483 being sent to Joseph-Vempilly alleging that he had failed to follow statutory requirements and FDA regulations.

FDA's allegations boil down to two main contentions: that Joseph-Vempilly "failed to ensure that the investigation was conducted according to the investigational plan," and that he "failed to maintain adequate case histories that record all observations and other data pertinent to the investigation on each individual" in the investigation.

To the former point, FDA alleges that the study had several deviations from the agreed-upon parameters, including two patients who were taken off of an inhaled corticosteroid, another who stopped using the corticosteroid, and a fourth patient who stopped using the corticosteroid one day prior to a checkup point. In all four cases, the patients were not excluded from the treatment randomization, FDA said, violating the protocol and "jeopardizing subject safety and welfare."

FDA said these deviations "raised concerns about the validity and integrity of the data collected at [the investigator's] site."

Falsified Data

The second set of allegations made in the Warning Letter pertains to the adequacy and accuracy of case studies maintained by the investigation, which FDA said it found lacking. Those case histories were supposed to include records of patient blood pressure, pulse rate and body temperature, but FDA said it found several instances when recordings were listed when they were not actually taken. Several progress notes in the case file documents indicated that "these measurements were not taken at every visit," but nevertheless were recorded.

FDA said it was unable to determine the extent of the alleged falsification, but said Joseph-Vempilly had "acknowledged" the falsification, and indicated that he had informed the institutional review board (IRB) overseeing the study upon being made aware of the problems in July 2011. The problems were blamed on a research coordinator who has since been terminated, according to his correspondence with FDA.

FDA, however, said his response was inadequate in that it did not provide sufficient information regarding corrective actions to be taken to avoid problems occurring in the future.

FDA Warning Letter to PI