Is it too risky to place healthy children in clinical trials when they don't suffer from the disease and won't benefit from being subjects?

That question will land on the desk of Health and Human Services Secretary Tommy Thompson sometime before the end of this year. His decision -- coming as Congress is poised to consider the first overhaul of medical research laws in 28 years -- could set a precedent for the Bush administration's approach to protecting children who participate in clinical trials.

The issue that faces Thompson stems from a notice tucked inside the Federal Register. The notice concerned a proposed clinical trial that would involve recruiting 450 children ages 8 to 10 who might be at risk for developing type 2 diabetes, a serious disorder that is on the rise in the United States, especially among teenagers and young adults.

But the children in the study would not actually suffer from the disease, and therein lies the problem for patient advocates.

"Children are not legally competent to volunteer for research," said Vera Hassner Sharav, president of The Alliance for Human Research Protection. "They have a right to be protected from experiments involving risks without a benefit for them."

Clinical trials involving children are supposed to be more closely scrutinized than those involving adults. The Office of Human Research Protection, which oversees the safety of subjects participating in federally funded research, was moved from the National Institutes of Health to the HHS secretary's office during the Clinton administration after a series of crises in clinical trials. One of the most serious incidents was the case of Jesse Gelsinger, a teenager who died at the University of Pennsylvania during a gene-therapy trial.

Research on adults is allowed to pose significant risk, and even offer little therapeutic benefit to the subjects who participate, provided they are adequately informed of the risks, and the study is expected to yield important information that could help others.

But federal rules governing human research consider research on children a special case. If the research poses more than a minimal risk, or even discomfort, it must offer the possibility of direct benefit to participants. Barring that, research on children must yield knowledge that is "of vital importance" to understanding and eventually treating a disease, and this knowledge cannot be gained by other means.

That's where the proposed diabetes study falls short, patient advocates contend. The research that would be conducted at the University of Washington School of Medicine and Seattle's Children's Hospital is aimed at understanding the metabolic changes that lead to higher than average rates of type 2 diabetes among Americans of Japanese ancestry.

Two-thirds of the children would be Japanese Americans and the rest Caucasian. The research would involve such invasive procedures as periodically drawing blood and dosing the children with glucose intravenously over the course of the multiyear study. Such procedures are generally not dangerous, but any procedure carries risk of infection or other complications.

Dr. Wilfred Y. Fujimoto, a leading diabetes researcher and co-investigator for the proposal, said the study is essential to understanding why Japanese Americans develop type 2 diabetes at twice the rate as the rest of the population.

"This research will help us learn why some children are at risk and how changes that occur before, during and after puberty affect this risk," he noted.

But Sharav, a patient advocate who served for two years on an advisory panel to the Office of Human Research Protection, said the study "does not even come close to meeting the ethical standards required under federal regulations."

By the time Sharav learned of the University of Washington proposal, it had already cleared a collection of review boards. The first hurdle was an ethics and safety panel known as an Institutional Review Board, or IRB, at the University of Washington. Ordinarily, if IRB found a proposal acceptable, it would allow the research to proceed. But in this case, IRB concluded that the study posed more than minimal risk to the children and would not benefit them directly.

As a result, the University of Washington panel kicked the proposal upstairs to HHS, as required by regulations. Once there, an Office of Human Research Protection panel subsequently recommended approving it. The panel was not unanimous in its decision, however, and one of the seven members argued that the proposal had "serious design flaws" and would not yield the information about diabetes the researchers were seeking.

Sharav and other patient advocates charge that HHS' handling of this case is an indication that the agency is loosening the standards that protect children. The office allowed only two weeks for public comment after the notice was published -- hardly enough time, patient advocates say, to find out about the proposed study, much less mount a credible argument against it. HHS has also refused to make public the proposal and full report of the advisory panel that supported the study.

Office of Human Research Protection officials were unavailable to comment about the proposal. A spokeswoman said the agency was not making the proposal or the panel report public because "it would interfere with the deliberative process."

Leonard Glantz, associate dean of Boston University's School of Public Health, and co-editor of the book, Children as Research Subjects: Science, Ethics, and Law, disagreed.

"You can't ask for comment and then not provide the material needed for comment," he said. "Otherwise the whole thing is just a sham."

Patient advocates argue that the pressure to recruit healthy children for research is increasing.

In 1997, the Food and Drug Administration proposed the "pediatric rule," which required the manufacturers of certain new and already marketed drugs to conduct studies on children. A year later, the National Institutes of Health issued regulations to include children in federally funded research studies whenever possible.

Since then, the number of proposals involving children that have reached the HHS secretary's office has jumped. Between 1983, when the rules governing research on children were first issued, and 2001, only three proposals failed the test of offering the possibility of direct benefit to the young subjects in the research. This year, there are six awaiting review.

FDA's pediatric rule was struck down by a federal district court on Oct. 17. Now, in addition to revamping the laws governing patient protection, Congress will also have to consider giving FDA new authority to require pediatric testing.