Former FDA Reviewer Reveals Shocking Intimidation and Retaliation Within Agency
Rosenberg: You have recounted that this is what happened to you with the nerve gas drug pyridostigmine.
Kavanagh: Yes, pyridostigmine is intended to be given preventatively in case of a nerve gas attack with the nerve agent Soman and it was used experimentally on Gulf War troops. After the first Gulf War, there were concerns it was linked to Gulf War Illness. Then prior to Operation Iraqi Freedom, the Defense Department (DOD) tried to have President Bush waive informed consent for pyridostigmine, even though it was still an investigational drug.
Kavanagh: Possibly because there is less hassle medicating troops if no informed consent is required. When President Bush refused to waive informed consent, the FDA approved pyridostigmine using the "Animal Rule" which allows the approval of drugs for human use based on animal data. It was employed because it was unethical to dose humans with the nerve agent Soman to see if pyridostigmine would actually prevent death. However, the way the drugs were used in the animal studies didn't reflect how they would be used in humans and resulted in misleading conclusions.
Rosenberg: Another FDA reviewer turned down pyridostigmine before you?
Kavanagh: Yes. I was assigned to re-review his conclusions regarding pyridostigmine and even before I began my review I was pressured to approve it and this pressure continued through nearly two dozen meetings with FDA management. After it became clear that I would not be pressured into an approval and it became apparent that it would be approved according to the animal rule in spite of the science, I raised an even stronger objection: not only did it not work against nerve agents other than Soman but pyridostigmine actually increased lethality in the presence of other nerve agents and we knew that Saddam Hussein was not using Soman and was instead using these other nerve agents.
Rosenberg: So you were just stating the obvious?
Kavanagh: This information was not secret--both FDA and DOD public documents acknowledge increased lethality with other nerve agents such as Sarin, and DOD and other government documents that are public also document that Saddam Hussein was not using Soman and was instead using these other nerve agents exclusively. Yet because I raised this as an objection, I was immediately replaced as the primary reviewer so that I could not document my concerns and so that pyridostigmine could be approved. It's since been proposed that if we ever face the prospect of nerve agents in the future, that this approval will be used as a justification to convince the President at that time to waive informed consent without presenting a full picture. Even though using pyridostigmine would likely only invite the use of nerve agents.
Rosenberg: Why would the FDA and DOD allow troops to be put in this kind of harm's way?
Kavanagh: I don't know and don't want to speculate. However senior managers made statements indicating knowledge that the approval was illegal. In any case, it was clear and known that use of pyridostigmine would interfere with the operation of our troops.
Rosenberg: Your training as a pediatric clinical pharmacologist has made you especially sensitive to drug risks for children. What are some of the unique drug risks children face?
Kavanagh: Pediatric approvals are based on the assumption that children will respond similarly to similar exposures. Yet dosages that are used for studies in children are often based on approved adult dosages rather than a scientific determination of whether children achieve the same or higher exposures than adults. This is because companies don't want to develop lower dosages for children if they don't have to. Thus exposure studies in children are done after the efficacy studies have been begun instead of before when it's needed. The exposure studies then may also use overweight children as well as too few children. Since no allowance is made for race, age, puberty, or actual weight and since there are differences in children's clearance of drugs, there are often higher exposures to active and toxic metabolites in children compared to adults. Thus there are often unnecessary risks with the doses that are approved.