December 23, 1997
Clifford C. Scharke, D.M.D., M.P.H.
Chief, Assurance Branch Division of Human Subject Protections
Office of Protection from Research Risks
6100 Executive Blvd. Suite 3B-01
Rockville, MD 20892-7507
Dear Dr. Scharke:
We are writing to request that the Office for Protection from Research Risks investigate a potential violation of federal research regulations that appears to endanger the human subjects.
A recently published article describes an experiment that occurred at the New York State Psychiatric Institute in New York City. Daniel S. Pine et al., Neuroendocrine Response to Fenfluramine Challenge in Boys, 54 Arch. Gen. Psych. 839 (September 1997). The experiment was partially federally funded according to the article, and the New York State Psychiatric Institute conducts research under a multiple project assurance which requires it to apply the federal research regulations in all experiments regardless of funding. The experiment involved thirty four healthy boys, ages six to ten,* who were younger brothers of convicted delinquents. They underwent a "challenge" experiment with the drug fenfluramine. The study was wholly non-therapeutic, and designed to test an hypothesis about the effect on a child's brain chemistry of living in an environment with poor parenting and other stressors. The boys "were all from impoverished families; 44% were African American and 56% were Hispanic." Id. at 840. The boys fasted for twelve hours prior to the test, and during the test had access to water only. An intravenous catheter remained in place for five and one half hours. During that period, a single oral dose of fenfluramine hydroxide was administered and blood was drawn hourly. The side effects of a single dose of fenfluramine frequently include anxiety, fatigue, headache, lightheadedness, difficulty concentrating, visual impairment, diarrhea, nausea, a feeling of being "high," and irritability. Matthew F. Muldoon et al., D, L-Fenfluramine Challenge Test: Experience in Nonpatient Sample, 39 Biological Psych. 761, 765 (1996). Moreover, ninety percent of subjects experience side effects from a single dose of fenfluramine. Id.
Notably, in September 1997, the FDA requested that the manufacturer of fenfluramine withdraw the drug from the market because the drug may cause heart valve damage in as many as thirty percent of the people who take it. Gina Kolata, Two Popular Diet Pills Are Withdrawn from Market, N.Y. Times, September 16, 1997 at A1. It has been known for several years that fenfluramine can cause an often fatal heart condition called pulmonary hypertension. Id.
Future studies are contemplated involving repeated fenfluramine challenges at multiple developmental stages for each subject. See Pine at 844.
This experiment does not provide either therapeutic benefit or a prospect of understanding a medical condition presented by these boys, since the subjects are healthy young children. Therefore, it is difficult to understand how this experiment could have been approved for participation of incapable subjects pursuant to 45 C.F.R. § 46.406(c). Moreover, since this experiment involves drugs, blood drawing and side effects that are not within these healthy boys' experience, the experiment appears to be prohibited by 45 C.F.R. § 46.406(b).
The hypothesis being tested that socially adverse child rearing conditions may affect brain chemistry in a way that contributes to chronic aggression is being studied elsewhere through experiments using hamsters and primates as subjects, and through review of records of child abuse and subsequent criminal activity by the victims. See Daniel Goleman, Early Violence Leaves its Mark on the Brain, N.Y. Times, October 3, 1995. Because this hypothesis can be studied without conducting non-therapeutic experiments on children, and because the risks and discomforts are significant, the propriety of this experiment is even more doubtful.
We request that you investigate this experiment, and take necessary steps to safeguard the human subjects and persons who may be subject to similar experiments at this institution. Please advise of the results of your investigation.
Thank you for your cooperation.
Very truly yours,
Disability Advocates, Inc. Disability Law Center
New York Lawyers for the Public Interest, Inc.
* See Daniel S. Pine et al., Platelet Serotonin 2A (5-HT 2A) Receptor Characteristics and Parenting Factors for Boys at Risk for Delinquency: A Preliminary Report, 1996 Am. J. Psych. 538, 539 (Describes a second experiment conducted on the same thirty four boys.)
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