Aventis subsequently hired Pharmaceutical Product Development (PPD) to conduct a study designed to enroll patients with respiratory infections in the offices of more than 1800 primary care physicians all across the country. Subjects were randomized for treatment with Ketek or Augmentin, another antibiotic.
In October 2001, doctors began enrolling subjects and were paid $100 for each patient they signed up, and another $150 when they submitted study results, as well as a final $150 after all questions were resolved, according to the May 1, 2006 WSJ.
The potential for money-making by doctors enlisted for this study was enormous. A fact that obviously did not go unnoticed by certain physicians who signed on to the study.
When the AIDAC reconvened to consider the study, the FDA presented it to the panel without disclosing that the agency's Division of Scientific Investigation and Office of Criminal Investigation were investigating both the conduct and integrity of the study. Without the benefit of this information, the AIDAC voted to recommend the approval of Ketek.
In the end, a March 25, 2004 memorandum, prepared by the Division of Scientific Investigations titled, "DSI Recommendations on Data Integrity," states that Study 3014 involved "multiple instances of fraud" and that "the integrity of data from all sites involved in [the] study ... cannot be assured with any degree of confidence."
In a press release on May 1, 2006, Senator Grassley said he was concerned about the FDA's complicity with the drug maker and subsequent failure to ensure the integrity of a pivotal study about the benefits and risks of Ketek. Specific allegations under investigation by the Senate Committee include that FDA management:
(1) accepted the resubmission of a new drug application for Ketek, which included fraudulent data in support of approval;
(2) presented fraudulent study data to an advisory committee tasked with recommending Ketek's approval or disapproval;
(3) instructed FDA scientists appearing before an advisory committee that they should present fraudulent data because discussing issues regarding data integrity and the conduct of the safety study would not be "productive;"
(4) approved a pediatric clinical trial, involving infants as young as six-months old, despite concerns related to known toxicities, including hepatic, visual, cardiovascular, and vasculitic adverse events; and
(5) continued to knowingly cite the fraudulent study in publicly released safety information on Ketek.
Given that the advisory committee had recommended conducting Study 3014 in the first place, theses allegations are "all the more outrageous," according to Senator Grassley.
The AIDAC members certainly would have been interested to know that the highest enrolling doctors were being investigated and that there appeared to be significant under reporting of adverse events.
For example, the investigator at the highest enrolling site, Dr Ann Campbell, was found to be enrolling patients when the clinic was closed, and patient consent forms had date modifications and signature inconsistencies.
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