http://www.nytimes.com/2001/07/03/health/03ASTH.html
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In releasing preliminary findings from its investigation into the
volunteer's death, the agency cited other violations in the Johns Hopkins
study, which was federally financed. They included failure to report a
previous unanticipated adverse reaction, in the first volunteer to
participate in the experiment; failure to follow the approved scientific
blueprint in preparing the experimental drug, and failure to inform
participants that the drug they would inhale, hexamethonium, was experimental. Johns Hopkins has not released findings of the autopsy it conducted and
has said that the cause of the volunteer's death has not been determined.
News organizations have identified the volunteer as Ellen Roche, 24, of
Reisterstown, Md. Johns Hopkins officials have questioned whether F.D.A. approval was
required for the asthma study. Nonetheless, they said they had temporarily
halted any studies involving drugs the agency had not approved for
experimental use until they consult with the agency. In the experiment, the inhaled hexamethonium was not intended to be a
therapy for asthma or in any way to benefit the three volunteers to whom it
was given. Rather, hexamethonium and another drug, methacholine, were used
to provoke the airways to constrict as they do in an asthma attack so the
researchers could study the drugs' effects on the airways during shallow
and deep breathing. The F.D.A. licensed hexamethonium as a pill for treatment of high blood
pressure in the 1950's, but the manufacturer withdrew it from the market in
the 1970's after new laws required that drugs meet both safety and
effectiveness standards instead of the earlier standard of safety, said Dr.
David Lepay, an F.D.A. official. The government requires that an ethics committee review any experiment
that uses federal money before it is carried out on a person. The review
board at Johns Hopkins approved the use of inhaled hexamethonium in the
experiment. Johns Hopkins officials said tonight that the researcher who led the
study, Dr. Alkis Togias, and the review board had not believed they needed
the agency's approval for inhaled hexamethonium because it was being used
for basic physiology tests and not to test its therapeutic value. In a statement released tonight, Johns Hopkins officials also said that
the university's ethics review board had "believed the lengthy consent
form was adequate in addressing known risks" and the issue would be
addressed by an internal review committee that is expected to deliver its
findings later this month. The death of the volunteer has come at a time of growing concern about
the safety of people who participate in drug trials and other experiments,
and it is one of a small number of deaths at hospitals that have come to
public attention in recent years. The death has also led to a number of investigations at Johns Hopkins in
Baltimore and by federal health officials. Johns Hopkins suspended the study but has come under criticism from
ethicists and researchers not connected with the university for failing to
report the death until mid- June, when it occurred on June 2. Much of the
information disclosed has resulted from requests filed by news
organizations under the Freedom of Information Act. The F.D.A. said that when the first volunteer in the asthma study
developed a persistent cough two days after inhaling hexamethonium on April
23, Dr. Togias's team at Johns Hopkins failed to notify the university's
institutional review board. The cough lasted from April 25 to May 3, the
F.D.A. said. The cough could be significant in the federal investigation because 24
hours after Ms. Roche inhaled hexamethonium, she developed a dry cough and
a flulike illness that progressed to severe inflammation of her lungs and
death. Johns Hopkins said that Dr. Togias believed the first volunteer's cough
"was due to an upper respiratory ailment going around the campus at
that time." Officials said they were "reiterating to faculty that all
unanticipated adverse events must be reported" to the review board. The F.D.A. also said that the Johns Hopkins researchers had not notified
the review board that had approved the experiment that they were changing
the way they prepared the experimental drug for the second and third
healthy volunteers by adding sodium bicarbonate and altering the concentration
of the saltwater solution. Johns Hopkins officials said that although Dr. Togias changed the
preparation "for the comfort of the volunteers," he should have
reported it to the review board. "We have reminded faculty of the
necessity to obtain approval for all changes to approved protocols,"
the university said.
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