Ronald Kavanagh: ... There is also irrefutable evidence that managers at CDER [Center for Drug Evaluation and Research] have placed the nation at risk by corrupting the evaluation of drugs and by interfering with our ability to ensure the safety and efficacy of drugs. While I was at FDA, drug reviewers were clearly told not to question drug companies and that our job was to approve drugs. We were prevented, except in rare instances, from presenting findings at advisory committees. In 2007, formal policies were instituted so that speaking in any way that could reflect poorly on the agency could result in termination. If we asked questions that could delay or prevent a drug's approval - which of course was our job as drug reviewers - management would reprimand us, reassign us, hold secret meetings about us, and worse.
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I think most people would be shocked at how malleable safety data is... I have seen new drug reviews where none of [the necessary safety studies and evaluations] were done by the medical safety reviewer... For example, human clinical pharmacology trials are typically done in Europe, yet clinical pharmacology reviewers at FDA have been barred from analyzing this information... Certain serious and potentially lethal adverse events that eventually resulted in a drug being withdrawn from the market would not have had any mention of the adverse events made in the labeling at all. On top of that, I frequently found companies submitting certain data to one place and other data to another place and safety information elsewhere so it could not all be pulled together and then coming in for a meeting to obtain an agreement and proposing that the safety issue is negligible and does not need further evaluation.
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During development, if reviewers say things that companies don't like, they will complain about the reviewer or they will call upper management and have the reviewer removed or overruled. On one occasion, the company even told me they were going to call upper management to get a clear requirement for approval that they did not want to fulfill eliminated, which I then saw happen. On another occasion a company clearly stated in a meeting that they had "paid for an approval."
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Sometimes we were literally instructed to only read a 100-150 page summary and to accept drug company claims without examining the actual data, which on multiple occasions I found directly contradicted the summary document. Other times I was ordered not to review certain sections of the submission, but invariably that's where the safety issues would be. ...if you found issues that would make you turn down a drug, you could be pressured to reverse your decision or the review would then be handed off to someone who would simply copy and paste whatever claims the company made in the summary document.
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FDA's response to most expected risks is to deny them and wait until there is irrefutable evidence postmarketing, and then simply add a watered down warning in the labeling. In fact, when patients exhibit drug toxicity, it is usually attributed to an underlying condition... This also allows the toxicity to be dismissed as being unrelated to the drug in any way.
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For 18 months, the FDA kept quiet about the issue of SJS [Stevens Johnson Syndrome, a life-threatening skin condition where huge swathes of skin covering large sections of the body die and slough off and the mucus membranes are also affected] in children [who took Provigil or modafinil], while Cephalon continued off-label marketing at full steam. Later, I found that the FDA had internal documents that had the same conclusion as my analysis but they had been withheld from the advisory committee.
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FDA management can use the threat of jail for violation of the Trade Secrets Act, not only to discourage reviewers, but in my case they got Senator Grassley's staff to destroy the evidence I provided them. The threats, however, can be much worse than prison. One manager threatened my children - who had just turned 4 and 7 years old - and in one large staff meeting, I was referred to as a "saboteur." Based on other things that happened and were said, I was afraid that I could be killed for talking to Congress and criminal investigators. ...I believe that actual felonies may well have occurred.
