|
|||||
|
|||||
|
|
|
|
|
|
|
|||||
 |
 |
    |
|
|
|||
 |
|
||
|
|||
|
|
|
|
||||||||
|
U.S. Response: Some Experts Express Caution on New FDA Measures By David Ruppe When human testing is deemed impractical or unethical — such as against live smallpox, Ebola or anthrax — the new regulations, announced last week, allow FDA marketing approval based partially on efficacy testing on animals (see GSN, May 31). Some say the regulation change is useful because it can provide incentive to biotechnology companies to put increased resources into developing terror-defense drugs and vaccines with the knowledge they could be marketed even though human efficacy testing is not possible. “It seems to make the most sense. There’s no way you can test some of these bugs [and bacteria] on people without violating our laws … no other way to go around it except to use animal data,” said Gigi Kwik an immunologist and fellow with the Johns Hopkins University Center for Civilian Biodefense Strategies. “If you’ve got a potentially dread disease, what are the alternatives? What are you going to do? You test on animals,” said John Bailar, professor emeritus at the University of Chicago Department of Health Studies. Reliability Experts say there are risks, however, because animal testing has not always proved reliable in predicting drug and vaccine effectiveness in humans. “It isn’t as good as testing in humans,” said Bailar. “You can learn an awful lot from testing on animals, though you don’t learn as much [as] from testing on humans.” “Less than 25 percent of those drugs that have been shown effective on animals gets approval from authorities,” said Imre Szebik, of the Clinical Trials Research Group of the Biomedical Ethics Unit of McGill University in Montreal, who opposed the regulation change. Szebik described several potential pitfalls of using an animal-tested drug in an actual incident, including the following possibilities: the drug may not work at all, the anticipated necessary dosage may be too high, the toxic effects may be too frequent and severe or the dosage would need to be increased, causing greater toxicity. “Although a small fraction of drugs are not marketed due to commercial reasons, the rest — the vast majority — is discarded due to failure of efficacy … or because of toxicity problems,” he said. To address that issue, the new regulations tighten requirements for approval of animal tested products by demanding an analysis and explanation of how the drug or vaccine would work. “The barriers are a lot higher now” than they used to be, said Kwik, who praised that move. “If you can’t do the testing in humans, then you have to have a lot better idea about how it works … You have to take a more intellectual approach to how that drug is solving your problem.” Szebik said, though, that it can be difficult to predict when metabolic and other systemic differences between the animals tested and humans have a significant impact on the effectiveness of a drug. “Given this huge uncertainty, it is hard to think that a drug or vaccine in question could be evaluated with a much better certainty,” he said. If an FDA approved drug does not perform as hoped in a bioterrorist incident, aside from the possible consequences to human life, public trust might be undermined, he said. “Commercial advertising of a drug with no proven efficacy or toxicity may be misleading, undermine public trust in the drug evaluation system in general,” he said. In his view, the preferable alternative to the new regulations would have been to allow such drugs to be approved for research purposes only, which still could be administered by government authorities in an emergency. “I don’t see why the administration of a research drug or vaccine in itself should be a problem in a public health emergency situation if all the steps are well designed, planned and the public is informed in advance,” said Szebik. “The danger of putting a drug on the market with uncertain properties however, may cause false expectations.” Available Sooner The FDA said in a press release that it changed the regulations to help get essential drugs to the market more quickly. “The terrorist attacks of last fall underscored the acute need for this new regulation,” said FDA Deputy Commissioner Lester Crawford. The “action will help make certain essential new pharmaceutical products available much sooner — those products that because of the very nature of what they are designed to treat cannot be safely or ethically tested for effectiveness in humans.” Pharmaceutical companies have said there is a lack of funding for such products, which may not have an immediate market value. Research has been underway on a new vaccine for smallpox that would not have the side effects of the vaccine used to wipe out the disease in the 1960s and 1970s (see GSN, Jan. 29). The United States currently is purchasing and stockpiling enough of the old formula to vaccinate every person in the United States (see GSN, May 16). The FDA regulations apply only to efficacy testing. No changes were made to regulations concerning safety testing of drugs and vaccines, which can be established generally without using a deadly bacteria or live virus. The regulations also apply to products for reducing or preventing the toxicity of chemical, radiological and nuclear substances. Perhaps Not for Everyone Kwik says she personally would not chose to take a new smallpox vaccine proven effective only on animals over the currently available, potentially less safe smallpox vaccine. She adds, however, that for many people the risk of the side effects might be too great and a smallpox vaccine with fewer side effects approved under the new regulations could become the best alternative. “If I were immunocompromised, then I would be very interested in those results [of the animal testing], since I’m not able to use the vaccine that worked before,” she said. People with AIDS, for instance, would face greater risk of serious side effects from the vaccine currently used, experts said (see GSN, Nov. 21, 2001). With respect to other diseases for which no proven vaccine is currently available, the regulations could help make the only good option widely available, Kwik said.
| ||||||||||
Back to top
