Statement on Petition to Repeal DOD/FDA Regulation

May 7, 1996

Statement by Sidney M. Wolfe, M.D., Director
Public Citizen's Health Research Group
Concerning Petition to Repeal DOD/FDA Regulation Allowing
Waiver for Informed Consent for Experimental Drugs

The petition being filed today documents the extent to which the Department of Defense flagrantly violated the agreements it had made with the FDA concerning the use of experimental drugs during the Persian Gulf War. Pyridostigmine bromide (PB) and botulinum toxin were given to U.S. troops under investigational new drug (IND) exemptions with the added proviso that informed consent could be waived. In addition to terminating the regulation allowing waivers of informed consent, FDA should give serious consideration to sanctions against the DOD for widespread violations of the terms under which they were supposed to be operating. FDA's Division of Scientific Investigations has, over the years, investigated a large number of clinical investigators of drugs and brought sanctions against them for violations of the protocols under which they had agreed to operate and for violations of informed consent. Although there was a waiver of written informed consent in the case of these drugs, the DOD clinical investigators were not relieved of their obligations to inform the troops--including the 600,000 to whom PB was issued (400,000 of whom used the drug).

I will spend a few minutes reviewing the following two pages entitled Chronology of Pyridostigmine (PB) Cover-up. But first, I would like to briefly discuss the comparisons between pesticides and nerve gases as shown on the handout depicting the chemical structures of both of these classes of compounds. This is especially relevant in light of studies showing how the combination of PB use with pesticides has a marked enhancing effect (synergy) on their individual toxicities.

In summary, it is clear that the DOD knew much more than it told either the FDA or the 600,000 U.S. troops in the Persian Gulf about questions about the effectiveness of PB when used against soman with subsequent use of possibly inadequate levels of atropine and about evidence concerning the use of PB in nerve gas attacks employing either sarin or VX. In the latter instances, according to data the DOD almost certainly had before the commencement of the Persian Gulf War, the use of PB might actually "adversely affect the efficacy of atropine and 2-PAM as antidotes for VX and sarin intoxication."

Chronology of Pyridostigmine Bromide (PB) Cover-up

August 13, 1990

An Army paper based on Aberdeen experiments is presented at the American Society of Pharmacology and Applied Therapeutics meeting in Milwaukee, Wisconsin. The conclusion of an animal study, referring to the usefulness of PB pre-treatment followed by subsequent use of approved antidote drugs, was "this [PBI adverse effect decreases protection against VX [a nerve gas]-induced lethality (att 1).

December 21, 1990

FDA publishes in the Federal Register the DOD-requested regulation allowing case-by-case waivers of informed consent.

December 28,1990

DOD writes to the FDA requesting waiver of informed consent for PB. Letter states that PB is effective against soman--referred to as GD in the request--but omits any mention of the lack of effect of PB (or deleterious effect, partially undoing the protective effects of the approved antidotes) if other types of nerve gas such as sarin or VX are used (att 2).

January 8, 1991

FDA approves a waiver of informed consent for PB (att 3). The letter from FDA Commissioner Kessler states, based on the incomplete information supplied by the DOD, that "there is no satisfactory alternative therapy for the prevention of the effects of exposure to organophosphorus nerve agents." [this class of compounds includes soman, sarin, VX and tabun]. By this time the DOD is surely aware but did not inform the FDA that against nerve gases such as sarin and VX, PB pretreatment could actually worsen the protection troops would otherwise get from using antidotes such as atropine and 2-PAM (see February 11, 1991 entry below). FDA conditions waiver on additional information being given to troops (att 4) but this information is itself misleading in that it states that "pyridostigmine, WHEN USED IN CONJUNCTION WITH ATROPINE AND 2-PAM, may be critical to your survival." It omits the fact that if PB is used and the nerve gas is sarin or VX, the use of this experimental drug might decrease that chance of survival by neutralizing some of the protective effects of atropine and 2-PAM.

January 11, 1991

Public Citizen, representing John Doe, a soldier in the Persian Gulf, files suit to block the waiver of informed consent .

January 17, 1991

The Persian Gulf air war begins.

February 11,1991

Another paper on the deleterious effects of PB in animals, again based on research done at the Army's Medical Research Institute of Chemical Defense in Aberdeen, Maryland--including some of the same researchers who did the work presented in August 1990 in Milwaukee (see above entry of August 13,1990)--is received by the journal, Fundamental and Applied Toxicology. Although this paper was not published until January 1992 (see att 5), for it to have cleared all of the layers of military bureaucracy, especially with its sensitive findings, the research and its conclusions must have been finished by November or December 1990, if not before. This study concludes that "...pyridostigmine pretreatment may adversely effect the efficacy of atropine and 2-PAM as antidotes for VX and sarin intoxication."

February 24, 1991

Persian Gulf ground war begins.

February 28, 1991

Persian Gulf ground war concludes.

According to information in the U.S. Senate Hearings, an estimated 400,000 of the 600,000 U.S. troops to whom PB was distributed actually used the drug. Given that it was known that the Iraqi nerve gas arsenal included sarin, it is fortunate that this chemical weapon was not used against U.S. troops during the war. Had there been, it is quite likely that many U.S. troops would have suffered much more nerve gas poisoning than they would have had they not been coerced to use the experimental drug, PB, without their informed consent or, as delineated in the petition being filed today, without much accurate information.

Attachments to this document are available by contacting Health Research Group