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Putting Children to the Test

Clinical drug trials on babies and youths can pose a dilemma for parents. But such programs shed light on how children react to medication.


Four weeks after the birth of their son, Ronnie and Michelle Higgins were stunned when they were asked to put him in a clinical trial for an antifungal drug.

Born 15 weeks premature, he had been expected to endure a long hospitalization crammed with drug treatments, tests and possibly surgery. And when he developed a fungal infection, they knew additional medication would be required. But an unproven drug?

"I found the idea of a clinical trial very scary," Michelle Higgins says.

Letting a child participate in the testing of a drug does carry some risks--and it's a decision that more parents are making.

A federal law passed in 1997 gave drug companies an incentive to test products in children by offering a six-month patent extension on drugs so tested. And in December, the Food and Drug Administration began requiring that new drugs deemed important to children--or even commonly used in children--include labeling on safe pediatric use.

As a result, the number of medications being tested in children has jumped from 114 in 1990 to 217 last year, according to the Pharmaceutical Research and Manufacturers of America. Most doctors agree there's a need for such research--and have long pushed for it.

After all, about 400 drugs commonly used in children--and 70% of all medications--bear no labeling information on safety and efficacy for them, says Dianne Murphy, associate pediatrics director at the FDA. Doctors typically prescribe the drugs simply hoping they'll work as they do in adults. With the new clinical trials, 120 medications could carry labeling for children within five to 10 years.

Still, "if a trial is for a new [drug], you can't really give people a good idea of all the types of possible side effects," says Jeff Goad, an assistant professor at the USC School of Pharmacy.

The possibility of serious harm became apparent during research on the drug Propulsid, for gastroesophageal reflux, in 1999. The FDA reported that 24 children being treated died of cardiac arrhythmia--some while involved in clinical trials. The drug's manufacturer, Johnson & Johnson Co., withdrew it from the market last year, although there is dispute over how much of a role the drug played in the infants' deaths.

But the case points to the agonizing choice facing doctors and parents: Test drugs in children or allow untested medications to be given to them. Even before the dangers of Propulsid were clear, doctors were enthusiastically prescribing the drug for babies despite the fact that the label carried no information on safety and effectiveness in children.

"There is this difficult dilemma as to which situation presents the most risk"--giving untested medications to children or doing clinical trials in children, says Christopher Milne, assistant director of the Tufts University Center for the Study of Drug Development. "But I think the evidence is coming down on the side of testing these medications in children."

Prescribing "adult" drugs to children has its own dangers, experts note. In the 1960s, numerous newborns died from the antibiotic chloramphenicol. And many other drugs have proved to be harmful in children in ways that were not discovered during testing in adults. For example, sulfa drugs were found to cause jaundice in newborns; the painkiller fentanyl led to withdrawal symptoms in kids; and the antibiotic tetracycline was found to stain the teeth of young children.

Among the major proponents of pediatric drug testing in children have been AIDS advocates, including the late Elizabeth Glaser, who said children were dying of the disease because of the lack of pediatric drug data.

Moreover, several recent studies have indicated that dosage in children does not work as doctors had hoped--that many children are receiving too much or too little of various medications.

Some trials have actually had immediate benefits for their participants. For instance, the standard medication for the Higgins baby's fungal infection can be toxic to the kidneys, particularly risky for such a young patient. The parents participated in the trial, and the baby is now doing well.

That antifungal drug study resulted in a change in treatment philosophy by demonstrating that the new medication was as effective but less toxic, according to a November paper in the journal Clinical Infectious Diseases.

"We're relieved now," his mother says, "because he could have been in another hospital where the experimental drug wasn't available and he would have received the toxic drug."

A Perception of Emphasis on Profit

Several U.S. children's hospitals, Children's Hospital of Orange County among them, are planning research centers to handle the growing demand for clinical trials.

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