New FDA drug category proposed by military

Designation would apply to battlefield drugs

A proposal to create a new category of Food and Drug Administration (FDA) licensure for drugs used by the Department of Defense (DoD) against nuclear, biological, and chemical threats has caused a stir in human research circles.

One of the authors of the proposal says the goal isn’t to weaken human subjects protection standards for those on the front lines of potential bioterror attacks, but simply to allow for the special circumstances of dispensing drugs in emergency situations such as wartime.

At the center of the issue is an important question: Should soldiers preparing for war or already on the battlefield be treated as research subjects?

"The military obviously has an interest in their personnel being as prepared as they possibly can make them, which includes protection from chemical and biological weapons," says Jeffrey Kahn, PhD, MPH, director of the Center for Bioethics at the University of Minnesota in Minneapolis. "So there’s an issue about whether that category of soldier should be considered research subjects or people who are needed to be trained and ready for the battlefield or some combination of those two. You can certainly argue that they are both. And the way you answer that question is going to make a difference in what protections you think ought to be in place."

In emergency circumstances such as preparation for war, following the more traditional FDA drug approval process isn’t just impractical — in some cases, it’s unethical, says Col. Arthur O. Anderson, MD, chief of the Office of Human Use and Ethics, U.S. Army Medical Research Institute of Infectious Disease (USARMIID) in Frederick, MD.

"It is immoral for us to get our products licensed with human clinical efficacy because in order to have a valid clinical trial, people are going to die — healthy people," says Anderson, co-author of the military proposal.

Anderson says his October 2002 memorandum was based on an assessment of the use of vaccines and treatments for diseases such as anthrax and smallpox, and weapons such as nerve gas in previous wars, including the first Gulf War.

He says that while innovative treatments are being developed for these purposes, their availability and use are restricted by elements of the federal Food, Drug and Cosmetic Act. Among the problems he identifies:

• Requiring human efficacy testing for drugs designed to treat diseases that are virtually unknown outside of their use in bioterrorism. Anderson argues that to conduct true clinical trials would mean exposing healthy subjects to these diseases or agents, which would be unethical.

"To do a valid clinical trial as required by the FDA, you would have to have placebo controls and immunized individuals and then you would have to challenge them with a lethal dose of agent, in order to have a valid argument that you have proven safety and efficacy against biological warfare," he says.

• Designation of many drugs that are in use in battlefield situations as "investigational." The problem with this designation is twofold: It undermines the confidence of soldiers who may believe they are being used as guinea pigs and it puts an undue burden on field surgeons, Anderson says.

"These gung-ho surgeons are saving lives," he says. "They don’t really have time to worry about whether they’ve deviated from a protocol. Those documentation and product accountability [requirements] are almost impossible to carry out on a battlefield."

Anderson’s memo suggests a new FDA designation: "Licensed for contingency," to be used when an advisory committee of DoD, FDA, and other experts determines that time or resources don’t permit a well-controlled clinical trial. The committee would review existing safety and animal efficacy information to determine whether and under what conditions the drug could be used.

Under this system, researchers could track the effectiveness of drugs because soldiers’ medical information can be stored on computer chips carried with them. The chips would carry such information as further treatment or possible adverse reactions.

Kahn says he has not seen all the details of the proposal yet, but notes that in general, it’s accepted that soldiers represent a unique circumstance when it comes to the use of vaccines and drugs.

"At some level, part of the deal when you enlist in the military — and realize that we’re not conscripting people here, they’re all volunteers — is you agree to give up some of the liberties you might otherwise have as a citizen of the United States," he says. "I think some different rules may apply. I don’t think you suspend all of your liberties or your right to certain protections as a subject in research. But I think the needs of [military] readiness alter the way we should think about how much testing must be done before these agents are used more widely on the population of the military."

He says that a system with some safeguards to bring forward drugs that show promise of effectiveness could be a sensible intermediate approach between no testing at all and the normal full FDA approval process.

One important question, Kahn says, is whether soldiers have a "right to withdraw," whether they can choose not to take a drug if they’re concerned about its safety. Previously, soldiers have been court-martialed for refusing anthrax vaccinations.

"Informed consent means there’s an option not to participate, and then what happens to those people?" Kahn asks.

While Anderson says no official action has been taken on his proposal, a recent FDA change creating a "streamlined investigational new drug (IND)" process has addressed some of his concerns.

FDA officials were unavailable for comment for this article, referring questions to the DOD. But previous published reports have outlined a streamlined IND process now in use that includes informed consent, use of an IRB board to review the protocol, and collection of outcomes data.

Anderson says any drug used under these conditions would be subject to animal efficacy and human safety testing. But he says he knows that arguing for any difference in standards for drugs used by the military could be a hard sell to some.

"It’s a You’ve-got-to-trust-me’ kind of thing, and obviously the military is always what people don’t trust, because we’re the government," he says.