OHRP suspends Johns Hopkins Research license for Fed funded research

July 19, 2001

The death of Ellen Roche, a healthy young woman before she was killed in a fatal hexamethonium inhalation experiment at Johns Hopkins University, has opened Pandora’s box, demonstrating that the safety of human research subjects has had a very low priority.

Following an on-site investigation of Johns Hopkins University research, the Federal Office of Human Research Protections (OHRP) took action. In its letter dated July 19, addressed to Edward Miller, Dean and CEO, Gregory Schaffer, President and Chi Van Dang, Vice Dean for Research ,OHRP suspended the University’s Federal license (MPA) to conduct human research involving human subjects:

All Federally funded research was suspended at: the Johns Hopkins University School of Medicine (JHUSM), the Johns Hopkins University School of Nursing, the Johns Hopkins Hospital, the Johns Hopkins Bayview Medical Center, the Gerontology Research Center of the National Institute of Aging-Bayview Campus, the Kennedy-Krieger Institute, and the Applied Physics Laboratory. Hopkins is the nation’s highest recipient of Federal research grants–$301 million last year. According to AP Hopkins has ranked No. 1 for the ninth straight year:

“OHRP has directed the above-referenced institutions to suspend accrual of additional subjects in all Federally supported research. Research interventions in previously enrolled subjects may continue only where it is in the best interests of the subjects. Reinstatement of MPA M-1011 must be approved by OHRP (or an alternative written Assurance must be approved by the supporting Federal department or agency) prior to resumption of any Federally supported research activities involving human subjects at the above referenced intuitions.”

In its letter of findings (July 19) to JHUSM OHRP cited multiple violations with Federal regulations, some as basic as:

a. failure “to obtain published literature about the known association between hexamethonium and lung toxicity. Such data was readily available via routine MEDLINE and Internet database searches, as well as recent textbooks on pathology of the lung.”

b. failure “to obtain sufficient information regarding the source, purity, quality, and method of preparation and delivery of the hexamethonium used in the research” prior to approval.

c. Failure by the IRB to “receive or request from the investigators any information regarding the pharmacology and toxicity of inhaled hexamethonium in animals or sufficient information regarding the safety of inhaled hexamethonium in humans.”

d. “The informed consent document failed to indicate that inhaled hexamethonium was experimental and not approved by the FDA. Furthermore, hexamethonium was referred to as a “medication” in the informed consent document.

These are just the some of the indicators that the research protection system is a sham–OHRP’s findings demonstrate that the IRB served as mere rubber stampers approving protocols en masse–without minimal information. As has been repeatedly demonstrated since September 1997, major research institutions can no more be entrusted to protect the lives of human research subjects, than stock traders can be entrusted to protect the interests of small investors.

How many more preventable research casualties will there be before Congress takes action? A law is needed and an independent oversight and enforcement agency is needed to protect human subjects from overreaching investigators.

Johns Hopkins Medicine: http://www.hopkinsmedicine.org
Office of Human Research Protection: http://ohrp.osophs.dhhs.gov

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Government Suspends Federally-Funded Research at Johns Hopkins University Wire
July 19, 2001
Filed at 4:50 p.m. ET

Government Suspends Federally-Funded Research at Johns Hopkins University
By THE ASSOCIATED PRESS

BALTIMORE (AP) — The government has suspended federally funded research on human subjects at Johns Hopkins University following the death of a healthy volunteer during an asthma experiment, the school said Thursday. The move comes just three days after the university suspended human research by the doctor whose experiment went awry in June, causing the death of 24-year-old Ellen Roche.

Officials with the federal Office of Human Research Protection did not immediately return a call seeking comment. Hopkins called the agency’s decision “unwarranted, unnecessary, paralyzing and precipitous.” “We strongly believe that this action was taken in utter disregard of patients’ health and potentially of life,” Hopkins Medical School spokeswoman Joann Rodgers said. The school said the effect could be devastating for ongoing clinical trials.

Hopkins receives more federal research dollars than any other medical school — $301 million last year, making it No. 1 for the ninth straight year.

The university has acknowledged full responsibility for Roche’s death June 2 and suspended 10 projects led by Dr. Alkis Togias. Togias remains on staff and faces no other disciplinary action.

Medical school officials said Roche likely died from inhaling the drug hexamethonium, which restricts airways.

Hexamethonium was used widely as a tablet in the 1940s and 1950s to treat hypertension, but the Food and Drug Administration later withdrew its approval. It never was approved as an inhalant, which was the way it was used in the Hopkins study, the FDA said.

Earlier this month, a preliminary federal report said researchers should have sought FDA approval for experimental use of hexamethonium. Togias’ study was funded by the National Heart, Lung and Blood Institute, a division of the National Institutes of Health. It was intended to help doctors learn how the body fights asthma by inducing asthmatic symptoms in healthy lungs.

Roche, a lab technician in the Johns Hopkins Asthma and Allergy Center, was one of three subjects who inhaled hexamethonium. The first developed a cough lasting a week. The third had no symptoms.

Roche also began coughing and died a month later while hospitalized. An internal review was mixed on whether Togias should have stopped the experiment after the first subject developed symptoms.

The panel noted that existing information about the danger of the drug wasn’t published in the research subject consent forms, but said disclosing the information may have had little effect on the outcome.

The report stopped short of blaming Togias for Roche’s death and said the experiment was well-supervised.

On Monday, the university said it is imposing additional supervision on the hundreds of studies it conducts each year. An external investigation of the fatal research is expected to begin later this month.

Some members of Congress have suggested requiring new standards and reviews for researchers who want federal funding. Others have called for the establishment of an accreditation system for researchers.

Pressure for added protections has been building since the 1999 death of Jesse Gelsinger, 18, at the University of Pennsylvania four days after he was injected with a genetic drug designed to correct a liver disorder. Researchers said he died because the protein used to carry new genes into his damaged liver triggered a major immune system response.

A federal investigation found researchers enrolled ineligible patients such as Gelsinger and had failed to warn patients that two monkeys used in the same experiment had to be put to death because they developed serious side effects.

Copyright 2001 The Associated Press