Pubdate: Tue, 03 Jul 2001
Source: Pittsburgh Post-Gazette (PA)
Section: Pg A3
Copyright: 2001 PG Publishing
Author: Lawrence K. Altman, The New York Times


Washington--The Food and Drug Administration yesterday said Johns Hopkins 
University researchers who conducted an asthma experiment that led to a 
healthy volunteer's death last month had not sought or received FDA 
approval to use an unlicensed drug that was involved in the experiment.

In releasing preliminary findings from its investigation into the 
volunteer's death, the agency cited a number of other violations in the 
Johns Hopkins study, which was federally financed.

They included failure to report a previous unanticipated adverse reaction 
in another healthy volunteer who went first 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, 
mexamethonium, was experimental.

Johns Hopkins, in Baltimore, has not released findings of the autopsy it 
conducted and has said that 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 FDA approval was required 
for the asthma study; nonetheless, they said they have temporarily halted 
any studies involving drugs for which the FDA has not given permission for 
experimental use until they consult wih the drug 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 FDA licensed hexamethonium as a pill for the treatment of high blood 
pressure in the 1950s, but the manufacturer withdrew it from the market in 
the 1970s after new laws required that drugs meet both safety and 
effectiveness standards instead of the earlier standard of safety, said Dr. 
David Lepay, an FDA 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 last night said the researcher who led the study, 
Dr. Alkis Togias, and the review board did not believe that they needed FDA 
approval for inhaled hexamethonium because it was being use for basic 
physiology tests and not to test is therapeutic value.

Johns Hopkins officials also said its ethics review board "believed the 
lengthy consent form was adequate in addressing known risks," and that the 
issue would be addressed by an internal review committee 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.

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 June 2.

Much of the information disclosed has resulted from requests filed by news 
organizations under the Freedom of Information Act.
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