Scientists and several veterans groups said the U.S. Food and Drug Administration ignored evidence indicating serious safety concerns when it recently approved a drug called PB to protect soldiers from poisoning by a nerve gas.
The veterans groups, including Gulf War Vets, whose members first took PB in 1991 while serving in Iraq, said they plan to urge Congress to investigate the science behind the FDA’s decision.
The groups point to a 1999 study by the RAND Corporation and a 2000 report from a panel of experts convened by the Institute of Medicine, both of which concluded pyridostigmine bromide, or PB, could not be ruled out as causing Gulf War syndrome. This is a set of symptoms that includes fatigue, cognitive problems, muscle pain and weakness, and sleep disturbances experienced by some Gulf War vets who served in Iraq in 1990-1991.
Despite these studies, the FDA approved the drug last week for use in soldiers to prevent poisoning by a nerve gas called soman that can kill within a matter of minutes.
Another controversy about FDA’s decision is that PB is the first drug approved under a new rule that does not require human studies. The rule allows treatments for biological and chemical weapons to be approved on the basis of animal data because it would be unethical to expose humans to deadly agents.
In addition, the FDA did not convene an advisory panel of independent experts, as it normally does, and the agency did not consult with researchers considered to be experts in the area.
Beatrice Golomb, an assistant professor of medicine at the University of California, San Diego and the author of the RAND report, said the FDA’s approval of PB is “concerning,” in particular because “a substantial amount of research has been done since (the 1999 report) strengthening the case” of a link between PB and Gulf War syndrome.
A study released by Duke University researchers just two weeks before the FDA approved PB found a combination of three chemicals — including PB — to which Gulf War veterans likely were exposed caused testicular damage in rats. The researchers think this could explain the infertility and sexual dysfunction problems seen in some Gulf War vets.
Robert Temple, associate director for FDA’s center for drug evaluation and research, said he was not certain if the agency had reviewed the Duke study prior to approving PB.
He also acknowledged the agency decided not to conduct an advisory committee of independent researchers familiar with the topic because “we thought (the decision) was fairly clear cut.”
Sidney Wolfe, director of Public Citizen’s health research group, questioned how the decision could be “clear-cut” given there were no human studies conducted. He also noted the drug’s effectiveness at protecting against soman is questionable and there is concern it could worsen exposure to another nerve gas called sarin.
Rick Weidman, director of government relations with the Vietnam Veterans of America, noted “there is no peer-reviewed scientific study saying that PB is effective against soman and it’s safe to use.”
The agency’s decision not to hold an advisory panel meeting “is a serous problem because this would be the first drug … approved just on the basis of animal evidence so there’s more of a reason to subject it to very careful scrutiny,” said Wolfe, whose group filed a lawsuit challenging the experimental use of this drug in Gulf War vets in 1991. Public Citizen lost the lawsuit because the court ruled national security overrode the health concerns of soldiers.
The decision to forgo an advisory committee also meant the FDA did not have to take public comment on PB.
The agency also did not consult with the members of the IOM committee, Golomb, or any other experts in the area, Temple said.
Instead, the FDA “just read the reports” on PB and relied on studies in guinea pigs and monkeys to reach the conclusion the drug was safe and effective, Temple said. The safety of the drug was also backed up by its use for treating patients with myasthenia gravis, a disease that affects the muscles and for which PB was first approved in 1955.
Temple also asserted the major studies on the effects of PB in soldiers “concluded that you really couldn’t make the case pyridostigmine had anything to do with the Gulf War syndrome.”
This is an interpretation that runs in direct contradiction with those of the experts involved in those studies.
“My reading of the literature suggests there is an increasing and persuasive amount of literature to suggest … pyridostigmine contributed to the clinical health problems in Gulf War Veterans,” said Golomb, who also serves as science director for the Department of Veterans Affairs’ research advisory committee on Gulf War illnesses.
Golomb noted the FDA did not consult with her before deciding to approve PB and she is “puzzled why they didn’t talk to me.”
Harold Sox, chair of the IOM committee on health effects associated with exposures during the Gulf War that issued a report in 2000, said in presenting the committee’s report in 2000 there was “sufficiently strong (evidence) to demonstrate an association between exposure and the immediate onset of mild, transient symptoms.” Sox, who chair of Dartmouth’s department of medicine at the time and is now editor of the Annals in Medicine, noted that the long-term side effects were uncertain.
“In other words,” he said, “we don’t know if they occur, and we can’t be certain that they don’t occur.” The committee recommended further study of the link between PB and Gulf War illness.
William Winkenwerder, assistant secretary of defense for health affairs, said, “We are pleased with the FDA decision to license pyridostigmine bromide … As an FDA-approved drug for use as a pretreatment against the chemical warfare agent soman, PB provides a critical safeguard against a chemical threat.”
One concern among Veteran groups is if PB will be mandatory or voluntary for soldiers. A source at the Department of Defense, who spoke on condition of anonymity, said, “There hasn’t been any kind of decision made if it would be mandatory or even if they are going to use it.” The source added, however, that since “PB is FDA-approved a commander would be able to order it’s use.”
Several members of Congress still have concerns about PB’s involvement in Gulf War illness, including Rep. Christopher Shays, R-Conn., chair of the House subcommittee on national security, international relations and veterans affairs.
“The approval is very troubling because PB is still under investigation as a contributing factor in Gulf War illness,” Shays’ spokeswoman Betsy Hawkins said. “Just as troubling is how the doses will be set in humans since the approval was based on animal data,” Hawkins said.
Shays plans to look into how the approval of PB in the absence of human tests could impact a veteran’s ability to obtain compensation if he or she suffers an adverse reaction to it.
“We would be looking at how the fast-tracking of some of these compounds is getting them into use before adequate testing on humans has been done,” Hawkings said.
“The challenge is going to be for (a soldier) to have adequate medical records and data to demonstrate a link (between PB and an adverse reaction),” she said. “If an item has been fast-tracked and the testing has not been done it might be more difficult to prove. So we will be looking at both those things and how it’s happening and why.”
Another issue is whether PB will impair soldier’s ability to function in a combat situation. John Richardson, who retired as a Lt. Colonel in the Air Force Reserve, flew F-16 jets as a member of South Carolina’s Air National Guard and said the drug made him unable to operate as a pilot. His first dose of PB made him nauseous for two or three hours, he broke out in sweats and his eyes teared.
“I would have not been able to effectively accomplish a combat mission while taking that pill,” Richardson said. “I don’t think someone driving a tank would be able to do much better.”
All the major veteran groups, including the American Legion, the Veterans of Foreign Wars, the National Gulf War Resource Center and the Vietnam Veterans of America, will write a joint letter to FDA, the Department of Defense and the Department of Veterans Affairs objecting to the approval of PB, said Steve Robinson, a spokesman for the NGWRC, which represents Gulf War Vets.
The letter will also be sent to members of Congress asking them to look into the issue, said Robinson, who served as an Army Ranger in the Gulf War.
“It does not pass the common sense test,” Robinson said. “There’s too much science that says it does harm.”
The manufacturer of PB, ICN Pharmaceuticals of Costa Mesa, Calif., did not return phone calls from UPI.
