Suffer the little children in the search for cures

By Dan Vergano, USA TODAY

Was the death of Ryan Lucio -- and of children in a few other cases -- an isolated tragedy or the inevitable byproduct of a wide-ranging push for more children to take part in experimental drug tests?

The FDA has 640 active requests for studies by pharmaceutical firms on the effects of their drugs in children. At least 37,520 children are needed for these clinical trials, in which some receive a new drug and others the standard treatment.

The FDA requires such studies before approving drugs. But health officials have seen many children receiving adult drugs, ones untested on kids, through legal prescriptions.

To beat the problem, agency officials began a push for pediatric clinical trials six years ago: More than 40 drugs are now approved for use in children, and there is a greater understanding of how medicines act in young bodies. Last week, for example, the agency approved the leukemia drug Gleevec for children's use, the first pediatric cancer drug approved in a decade.

But critics warn that the pitfalls of testing more drugs on children are little recognized by doctors and parents. "The FDA is only trying to expand the market for drugs to children," says activist Vera Sharav of the Alliance for Human Research Protection. Regulations intended to protect children from participating in trials not directly beneficial to them -- a level of protection beyond that required for adult participants -- are being ignored in the rush to test new drugs, she charges in The American Journal of Bioethics.

Agency officials strongly disagree, saying the drive for more testing in children reflects a desire for increased safety in drug prescriptions. In 1997, the FDA offered "pediatric exclusivity" to firms marketing drugs approved for adults if they perform agency-requested studies of the drugs' effects on children. This exclusivity provides an extra six months of patent protection and prevents competitors from marketing copies of a medicine during that extension.

For a $2 billion-a-year drug, "that's $1 billion extra" in sales, says FDA pediatric drugs chief Shirley Murphy. "It has completely changed the attitude of the pharmaceutical industry towards children."

Since 1997, her agency has given 74 drugs exclusivity, products ranging from the cancer drug Tamoxifen to the anti-osteoporosis drug Fosamax. Plus, Murphy says drug tests show that old medical ideas that treated kids "like little adults," shaving adult doses to children-size using weight as the criterion, don't work.

Prozac, for instance, is now known to stunt kids' growth, something tests in adults wouldn't have considered. Other drugs require higher or lower doses than expected for kids.

In clinical trials, "tragedies happen. We don't want them to happen, but they do," Murphy says, but the benefits of new drugs for kids are part of the conversation. Some 194 new drugs are now in development for children, according to the Pharmaceutical Research and Manufacturers of America.

All this activity makes it more likely that parents of very ill children will become involved in a clinical trial, perhaps with little understanding of the stakes. "So much information parents need to know, the researchers never tell us," says John Rogers of St. Louis. He and his wife, Oksana, saw their 20-month-old daughter Daniella die last year, killed by a side effect of a drug she was being given in a clinical trial.

In January, the federal Office of Human Research Protection found that Washington University School of Medicine in St. Louis had failed to warn Daniella's parents of "reasonably foreseeable risks ... including liver failure and death," from the drug in "informed consent" documents required before anyone enrolls in a study.

"Our child got sick. We were desperate. Your child is your flesh and blood, so you're willing to go to extremes to get the best care," Rogers says. He says he thought getting his child into an experimental treatment center meant she was getting the best care.

But researchers in clinical trials have conflicting responsibilities that may interfere with providing the best care, notes bioethicist Erich Loewy of the University of California-Davis.

"The researcher is ethically committed to generating knowledge, truth, whatever. If along the way the patient is benefited, that is nice, but not the researcher's primary aim," Loewy says.

And about four out of five drugs in clinical trials don't pan out, neither benefiting nor harming patients, according to industry statistics. Still, a majority of patients (77% of respondents in a 2000 survey) join clinical trials to be cured, receive better care or earn extra money rather than to advance medical science.

Loewy suggests that patients in trials have a separate physician oversee their case, a doctor concerned only with the patient's health.

In many cases, very ill people may have no choice, Rogers acknowledges, but in others the option to pursue standard care may never be mentioned by physicians eager to enroll patients in trials of potentially lucrative drugs.

"It is all about money to researchers. It really is," Rogers says. "Parents need to ask hard questions before they enroll a child in a study."