WASHINGTON – A new Food and Drug Administration ethics panel said the advancement of science outweighed the risks of giving a stimulant to healthy children as young as 9.
The 11-member Pediatric Ethics Subcommittee gathered for the first time Friday to consider a proposal that would give a single 10 mg. dose of dextroamphetamine to 78 children. The study, led by Dr. Judith L. Rapoport, would use MRIs to reveal brain patterns as the children complete certain tasks.
At the heart of the study is a question Rapoport has pursued for 30 years: Do the brains of children with attention deficit hyperactivity disorder respond to stimulants in fundamentally different ways from normal children?
“How do you tell the difference between a child who really has ADHD and a child who doesn’t?” asked Daniel Pine, a child psychiatrist who is co-investigator on the project. He said the study, funded by the National Institutes of Health, could lead to tests that would diagnose the disorder more precisely.
Half the children in the study, all aged 9 to 18 years, already would have been diagnosed with ADHD. The study raised ethical concerns because half the participants would be healthy children.
Rapoport told the panel the dextroamphetamine dose was roughly equivalent to 50 mg. to 75 mg. of caffeine, about five cups of coffee. Household surveys have shown many healthy schoolchildren are exposed to higher doses of caffeine by drinking soda and ice tea, Rapoport said.
The researchers were sharply rebuked by Vera Hassner Sharav, president of the New York-based Alliance for Human Research Protection.
“Why are we even considering using children as human guinea pigs?” Sharav said. She said the message to poor children, lured by the $570 offered participants, would be “to earn money, sign up for drug tests. Amphetamine today. Cocaine tomorrow. Ecstasy next week.”
Alan Milstein, an attorney whose clients have included victims of clinical trials, quibbled with Rapoport’s characterization of the experiment’s risk.
“This is not an experiment with minimal risk,” Milstein said. “What will happen if one of these subjects has an extreme reaction to the single dose?”
The subcommittee’s recommendation to allow the research to go forward will guide the FDA Pediatric Advisory Committee, which meets Sept. 15. The ultimate ruling whether the trial goes forward, however, will be made by the Health and Human Services secretary, Tommy Thompson.
Members of the panel said they were comfortable with the safety of dextroamphetamine, in use since 1937 and approved for children as young as 3.
Dr. Laurence Greenhill, a New York child psychiatrist, said the drug’s effects are felt within 15 minutes, clear within five hours and, if given in the daytime, don’t interrupt nighttime sleep. There is no strong evidence that a single dose, especially given in the context of a clinical trial, would trigger later substance abuse, Greenhill said.
“I would have no problem giving any child in this age range … a starting dose of 10 mg.,” Greenhill said.
Panel member Dr. Norman Fost, a Wisconsin pediatric ethicist, asked for the worst that “might plausibly happen.” Greenhill said 1 in 100 younger children can become more irritable, restless, agitated and prone to tantrums.
Maryland pediatrician Dr. Richard Gorman said while he worked at a poison control center, children who accidentally took that much dextroamphetamine “would be observed at home and their parents would be told to call if they had symptoms.”
While healthy children will gain no direct benefit from participating in the study, science might win, panel members said.
The study is an extension of groundbreaking work Rapoport conducted in the late 1970s as the field struggled to understand ADHD.
“I think it was kind of a classic study that took a bold step and included individuals with no mental disorder,” Greenhill said of Rapoport’s earlier study. “I see this as another step in the advance of science.”
The panel also suggested trimming the amount paid to participants, provided it doesn’t make it impossible to recruit.
At $570 for 11 hours, “that’s actually $51 an hour. I would volunteer,” joked Dr. P. Joan Cheesy, a Tennessee infectious diseases expert.