AMA Calls for Studies of Psychotropic Use in Children

Researchers, clinicians, and regulators agree that conducting clinical trials of medications in pediatric populations is no easy task. First of all, pharmaceutical companies must find clinical investigators with the expertise to conduct pediatric studies. Physicians must convince parents to expose their children to unknown risk and subject them to monitoring and testing they would normally not need. The potential pool of recruits for pediatric studies is also inherently smaller than those on adults, simply because the population of children with the disease or disorder being studied is small.

In addition, children may not cooperate freely or completely with the strictness of accepted research methods. And rating symptoms of illness, especially psychiatric illness in children, is even more subjective than it is in adults. Researchers must also worry about redesigning methods of evaluation and monitoring. In the words of one researcher who presented testimony on the subject to the FDA, “you simply can’t draw a bucket of blood from babies.”

And then there are the ethical questions. For years, researchers have worried that studying children was unethical. Robert Ward, M.D., a professor of pediatrics at the University of Utah and an expert in ethics of pediatric studies, said he thinks the ethics concerns are largely coming to a close.

“Without controlled clinical trials, we are treating children with less than optimal information about effectiveness, dosing, and safety,” Ward said. “You have to ask the question—Which is more unethical? To do that, or to treat a child in a controlled clinical trial?”

But many still have great concerns. Placebo comparison is still the FDA’s gold standard in clinical trials; however, it is extremely difficult, said Ward, to get parents to sign informed consent when they really understand that their child has the potential to receive no active treatment at all.

To address these and other critical issues, the FDA released last month its “Guidance for Industry E11: Clinical Investigation of Medicinal Products in the Pediatric Population.”

While stating that “the pediatric population represents a vulnerable subgroup,” the guidance offers only general suggestions for review-board participation and guidelines for recruitment, consent, and minimization of risk. The guidance does note that “in order to minimize risk in pediatric clinical studies, those conducting the study should be properly trained and experienced in studying the pediatric population, including the evaluation and management of potential pediatric adverse drug events.”

But new data are being developed and analyzed, thanks to the FDAMA incentives and a new federal regulation that went into effect last December. The new rule gives the FDA the power to require pediatric studies for drugs that might directly benefit children. In fact, at the FDA’s discretion, approval of the use of a drug in an adult may be withheld, pending at least initiation of pediatric trials.

“The interest in developing the type of trials that need to be completed in children has been somewhat overwhelming,” said Dianne Murphy, associate director for pediatrics at the FDA. “The important thing is, you can’t simply decide to do any study—the FDA determines if there is a public health benefit.”

So far about 200 studies have been proposed by pharmaceutical companies, including drugs for allergies, asthma, and, yes, depression. The proposed research, Murphy said, could involve as many as 20,000 children. By contrast, only 11 studies were completed in pediatric populations from 1991 through 1997, Murphy said.

The AMA resolution, while not likely to influence the FDA’s stance on the issue, may play a role in the public’s mind.

“With this new policy, the AMA is focusing on the need for sound scientific evidence to support treatment of children with medications,” AACAP’s Fassler told Psychiatric News.