Pubdate: Tue, 03 Jul 2001 Source: Pittsburgh Post-Gazette (PA) Section: Pg A3 Copyright: 2001 PG Publishing Contact: http://www.post-gazette.com/ Details: http://www.mapinc.org/media/341 Author: Lawrence K. Altman, The New York Times UNAPPROVED DRUG USED WHEN TEST SUBJECT DIED 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. - --- MAP posted-by: Beth