FDA CONSIDERS DRUGGING HEALTHY KIDS FOR SCIENCE
WASHINGTON (AP)
- Is it ethical in the name of science to give a healthy child as young
as 9 a controlled substance? That's the dilemma facing the Food and
Drug Administration's Pediatric Ethics subcommittee at its first-ever
meeting on Sept. 10. The research, proposed by the National Institute
of Mental Health, includes healthy children among 9- to 18-year-olds
who would receive a single 10 mg. dose of dextroamphetamine.
The hoped-for payoff for
research: A better understanding of how healthy brains work differently
from those of children diagnosed with attention deficit hyperactivity
disorder.
The payoff for families:
$570.
Characterized by inattentiveness,
overactivity and impulsiveness, ADHD affects up to 5% of schoolchildren.
The disorder continues in roughly 60% of those youths as they age, although
experts say the disorder is underdiagnosed in adults.
Dextroamphetamine, the active
ingredient in such drugs as Dexedrine and Adderall, is prescribed commonly
to increase attention span and calm restlessness. Doses vary with children's
needs, with daily doses as little as 5 mg. or as much as 30 mg.
Judith L. Rapoport, chief
of child psychology at NIMH, within the National Institutes of Health,
conducted a similar trial 20 years ago. The same stimulant was given
to children at a higher dose. Researchers looked only at how the stimulant
changed children's behavior as they performed tasks. The stimulant improved
attention span in the children, regardless of whether they had ADHD.
The new trial would add magnetic
resonance images to map potential differences in brain activation patterns.
While Rapoport's trial is
little different from the earlier one, review boar ds that balance risk
vs. scientific gain have changed dramatically in 20 years.
Indeed, an NIH review panel
met twice and was unable to reach a consensus whether risk to healthy
volunteers would be too high in the new study. They kicked the sensitive
matter over the FDA's new pediatrics ethics subcommittee.
The study would involve 14
children with ADHD, 14 healthy children, 12 pairs of identical twins
and 12 pairs of fraternal twins. As the children completed specified
tasks, their brain activity would be captured by MRIs.
Comparing twins - one with
ADHD, the other normal - helps researchers tease out genetic explanations
of differences in response to treatment.
In September 2003, an NIMH
panel that reviewed the proposal's scientific merit called the program
an excellent submission. The panel noted that it would be the first
ADHD study to compare twins, which has been useful in past studies on
schizophrenia.
The panel that considers
a safety of human subjects, however, was troubled by the youngest tested
children's age and the potential for coercion because each participant
would be paid $570 for the 11-hour study.
The major stumbling block
was determined to be the risk of giving a class 2 controlled substance
to healthy children, which some fretted might breed future substance
abuse.
Children in the 1980 NIH
trial had no increased risk of drug abuse in the five years after the
trial ended, researchers say in the study protocol.
The most common side effects
among healthy children given a single dose of the stimulant in past
experiments was temporary insomnia and poor appetite. One brain-damaged
child exposed to the medication suffered hallucinations.
Many ethicists expect the
FDA subcommittee to use a primary litmus test: Does taking the stimulant
pose more than a minimal increase to risks that healthy children face
in everyday life?
Pearl O'Rourke, who oversees
human research affairs, interviewed the heads of six review boards at
Massachusetts General and Brigham and Women's Hospital.
"Five said they would
not approve this study. And all five said, 'But we wish we could,'"
O'Rourke said during a March 3 NIH discussion.
O'Rourke acknowledged that
the review boards struggle with murky federal regulations, tightening
case law, financing agencies that prefer pediatric studies and the threat
of negative media coverage.
"I live in dread fear
of what's going to be on the front page of the paper," she told
the audience. "So, when I heard this, three things hit my mind:
Kids, ohmigod! Psychiatric disease. And a class 2 drug."
The FDA panel could simply
approve the plan if it should find it carried great scientific weight,
said Dr. Douglas Diekema, director of medical ethics at Children's Hospital
in Seattle.
New Jersey attorney Alan
Milstein said that would be the wrong call.
Milstein, who represented
the family of an 18-year-old whose death in 1999 spurred greater federal
oversight of gene therapy trials, pointed to a recent Maryland Supreme
Court ruling. The court held that exposing healthy children to higher-than-minimum
risk in a medical study is unethical.
"They can't do this
study. It doesn't take a genius to figure out why they can't do it,"
Milstein said. "I can't believe that anybody is going to say it's
ethical to do this. It's not even a close call."
