Study didn't warn of deadly side effect
By Kathleen Kerr. STAFF WRITER
For several years, researchers at the New York State Psychiatric Institute failed to tell parents of troubled youths who were the subjects of research that a controversial drug tested on them posed a risk of a rare but deadly side effect - primary pulmonary hypertension, a heart and lung disease linked to long-term use.
The drug, fenfluramine, was pulled from the market last September at the request of the Food and Drug Administration after a widely publicized announcement by the agency and the Mayo Clinic last July that it had been linked to serious heart valve damage in dieters who used it for weight loss.
But it was only this February - long after most of the 100 participants left the study - that researchers changed their parental consent forms to reflect the fact that fenfluramine posed possible risks of pulmonary hypertension and heart valve disease. Parents had to sign consent forms to give permission for their children to take part in the study.
Most of the participants - whose parents had not been informed of the possible dangerous side effect of pulmonary hypertension - had left the study by September, 1997, when the FDA asked that fenfluramine be taken off the market. The heart valve problem emerged after many dieters began taking fenfluramine in combination with another drug, phentermine. But phentermine was not implicated in the heart valve disaster that drove fenfluramine from pharmacy shelves last fall.
While the youths studied received only one dose of fenfluramine, parents should have been fully informed, specialists in medical ethics told Newsday.
Fenfluramine - one of the so-called fen-phen diet drugs - induces the brain to release seratonin and can affect mood, sleep and aggressive behavior. The study observed the effects of fenfluramine on brain activity and was not meant to treat the youths, who were either severely depressed or at risk for suicide.
The institute has also come under fire for another study, which officials said was completed in 1995. In that study, 34 black and Hispanic boys who were the brothers of delinquents received a dose of fenfluramine so researchers could study its effects.
In the study in which the 100 adolescents participated, all were either severely depressed or at risk for suicide. Claudia Bial, a Psychiatric Institute spokeswoman, said the youths came from throughout the metropolitan area - including Westchester and New Jersey - and were referred by their doctors. Some came from Washington Heights, where the institute is located. Thirty percent were Hispanic and 70 percent were caucasian, Bial said.
Bial said the institute studied 98 of the teenagers between 1992 and 1997 and that those 98 youths had left the study by September, 1997. Bial said the institute temporarily cut short its study after the FDA action, but resumed it this year with two more adolescents and with FDA approval. Then on April 2, the institute again halted the study.
Leonard Glantz, a highly regarded professor of health law at the Boston University School of Public Health, said even though pulmonary hypertension had only been associated with the appetite suppressants when used for more than three months, parents should have been informed of the risk.
"What you want to do with consent forms, in general, is explain to people material risks," Glantz said. "A material risk is a risk that affects whether you consent or don't consent to the study."
The institute's deputy director, Dr. Jack Gorman, blamed adverse publicity for halting the fenfluramine study: "We decided to put this on hold until we decide that the study could be pursued without any media questions that distract us from our mission."
Gorman said the institute didn't list pulmonary hypertension on parental consent forms until February, 1998, because it hadn't been identified as a possible side effect until then.
But Audrey Ashby, a spokeswoman for Wyeth-Ayerst Laboratories, which marketed fenfluramine under the Pondimin name until last year, said the company changed its label in 1996 to include a warning about the risk of primary pulmonary hypertension.
"There was a change in the label; it was revised on Nov. 25, 1996, to include the information that the use of appetite suppressants for longer than three months is associated with a 23-fold increase in the risk of developing primary pulmonary hypertension," Ashby said yesterday.
The warning, in bold type, read: "Fenfluramine is an appetite suppressant, and appetite suppressants increase the risk of developing primary pulmonary hypertension, an often fatal disorder."
When the institute changed its parental consent form this February, the new warning read, in part: "Use of this medication has been associated with the development of serious and potentially life threatening medical problems (specifically pulmonary hypertension and heart valve damage). These problems have only been reported among individuals who had taken the medication for weeks or months. The risks of these serious side effects after one or two doses is unknown."
Gorman said there is no evidence the youths suffered any harm from the single dose of fenfluramine.
Gorman also confirmed that the institute paid $150 to parents who let their children take part in the halted study and brought them back for follow-up visits. Some medical ethicists contend such payments may wrongly sway parents to give consent.
The institute has already acknowledged paying $125 for children's participation in its fenfluramine study focusing on brothers of troubled youths. In that study, the institute observed the effect of fenfluramine on 34 boys - all black or Hispanic - who lived in Washington Heights. Gorman has said the study reflected the population around the institute.
"You're essentially asking them to rent out their kids to have research on them," Glantz said. "Paying parents to volunteer their kids for research is an abuse of power."
In the halted study, the teenagers received in-patient hospitalization for depression but Glantz said even that might be viewed as a kind of payment.
Copyright 1998, Newsday Inc.
Parents Never Knew of Test Risks / Study didn't warn of deadly side effect., pp A04.