By Kathleen Kerr. STAFF WRITER
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
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
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.
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