Category: Writing

In four studies funded by the NIH and conducted at Columbia
University in New York City during the early 1990s, 68 healthy children and 66
children diagnosed with attention-defi cit/hyperactivity disorder (ADHD) were
enrolled in a nontherapeutic experiment (with no potential direct medical
benefi t). The purpose of the study was to investigate possible correlations
between serotonergic activity and aggression. There are some data to indicate
that an increased secretion of serotonin may be associated with aggression.
Some of these children were identifi ed as having aggressive behavior. The rest
of the children were identifi ed as having potential aggressive behavior
because they had siblings who were incarcerated or had family, social, genetic,
or environmental factors associated with aggressive behavior. The rationale for
this experiment is that administering a dose of fenfl uramine could greatly
increase the rate of secretion of serotonin in the experimental group compared
with the control group, which could reveal an association between serotonergic
activity and aggressive behavior. Fenfl uramine is one of the active components
of the “Fen-Phen” antiobesity drug combination, which has signifi cant known
risks, such as cardiac damage. ADHD itself is recognized as a risk factor for
aggression. All children were African Americans or Latinos from very poor
environments, and all were receiving drug treatment. The children were given a
gift certifi cate of $25, and the parents were given $100 to $150 each. Incarcerated
siblings were identifi ed from sealed court records without permission from the
courts or the city administration. Afterward, the researchers contacted the
subjects and their siblings at their homes and identifi ed themselves as
persons conducting research funded by the federal government. The study was
approved by several IRBs. NIH study sections also approved the original
research proposal. The procedure required subjects to undergo a battery of
tests, including genetic tests. The subjects then underwent an overnight fast
and were administered a challenge dose of fenfl uramine, with blood samples
collected for several hours. Samples of spinal fl uid (by spinal taps) were
collected every 3 hours for 12 hours. Blood levels of serotonin were monitored continuously
through a vein catheter. Because the study offered no potential direct medical
benefi ts, it could not be approved under the federal designation 45 CFR 46.404
or 46.405 (category I or II). It could only be approved under designations
46.406 or 46.407 (category III or IV; see defi nitions above). In the fall of
1997, the human rights organization, Citizens for Responsible Care and Research
(CIRCARE), cofounded by one of the authors (Shamoo), called for an
investigation by the federal oversight agency, the Offi ce of Protection from
Research Risks (OPRR), the predecessor of the Offi ce for Human Research
Protections. CIRCARE also alerted the media and other advocacy groups. The
determination letter from OPRR claimed that using healthy subjects was
appropriate, whereas using ADHD subjects was not appropriate. Also, OPRR said
that the informed consent document did not adequately inform the parents.
Unfortunately, the OPRR determination was based on technical matters such as
whether there was a properly convened meeting of the IRB, not on substantive
matters concerning the ethics of the study (Shamoo and Tauer 2002, Koocher
2005).
• Were the risks to subjects minimized?
• Were the benefi ts suffi cient to justify the study?
• What kind of informed consent process could be adequate?
• Was the selection of subjects equitable?
• Was confi dentiality of subjects, family, or their
siblings protected?
• What can we learn from this episode?

Should the military conduct research on blood substitutes
with soldiers who are wounded on the battlefi eld and potentially could die
with no access to fresh blood? If not, should you do such research on civilian
trauma patients?

1. How would you design a system to ensure enrollment of
mentally ill individuals into research studies while protecting them from harm?
Why?
2. Should there be decisional capacity assessment for the
mentally ill? All of them? Why? When and how?