U.S. Suspends Human Research at Johns Hopkins After a Death

By GINA KOLATA

After investigating the death of a young, healthy volunteer last month in a research study at Johns Hopkins University, a federal oversight agency yesterday suspended almost all the university's federally financed medical research involving human subjects. One reason for its action, the agency, the Office for Human Research Protections, said in a letter to Hopkins, was that the ethics committee that approved the study in question had failed to take proper precautions to protect its subjects. Suspending research is an unusual step.

[Note: By July 24, the FDA and Hopkins had reached an agreement that allowed most/all of the ongoing research to resume, but the investigation continues ... most recent news: a 1978 study is being re-examined because researchers now recall that two participants in it had adverse reactions to hexamethonium].

Johns Hopkins receives more federal research money than any other university, $310 million last year. ...

The volunteer, Ellen Roche, died on June 2, a month after she inhaled an unapproved drug as part of a research study to examine the causes of asthma. Her lungs were destroyed, apparently by the chemical she inhaled, hexamethonium. She was 24 and a technician at Johns Hopkins [According to the research protocal, subjects were paid $365 for their participation. Roche work in the allery and asthma group at Hopkins,but not for the researchers, Togias.] Hopkins officials reacted with outrage ...

The continuing examination of what went wrong at Hopkins has raised broader questions about how tightly the government should regulate academic research. The Food and Drug Administration says scientists should seek its approval for any study involving new or unusual uses of drugs, but the agency does not police the universities to make sure they comply. Some researchers have sought F.D.A. approval, but others, like the researcher at Hopkins, have not. Hopkins says the F.D.A. has not made its policy clear....

"What we are talking about is a system of controls that works to protect human subjects," said Dr. David Lepay, who is a senior adviser for clinical science in the office of the F.D.A. commissioner. "Our regulations are fairly specific. It is not a question of how many subjects are in the study or whether the study is being used for purposes of marketing. What we are talking about is the study of an unapproved drug in a clinical investigation."...

"The F.D.A. has a double standard," said Dr. Bert Spilker, who is vice president for scientific and regulatory affairs at the Pharmaceutical Research and Manufacturers of America. "The standards for industry are much higher than those followed by academic investigators." ...

William Vodra, a former F.D.A. lawyer now working for the Washington law firm Arnold & Porter, said drug companies are used to getting agency approval and have entire staffs whose job it is to make sure the job gets done. Universities have no such resources, Mr. Vodra said, which could make it very hard to comply with F.D.A. regulations.....

[About this tragedy, obviously alot easier in hindsight to see the mistakes/possible mistakes. Gives me the willies, just thinking about it having done research myself, priding my self on good literature reviews and yet knowing how committees and individuals can get overburden/over-extended....anyway, the study took place and without clear guidance from the F.D.A., it seems]
Dr. Togias went ahead with his study, without applying to the F.D.A. After assessing hexamethonium's safety by searching the medical literature, he concluded that its main side effect was a possible transient lowering of blood pressure. The [university] ethics committee approved his study, which was to involve 10 healthy volunteers.

He then bought hexamethonium, sterilized it and began giving it to his study subjects, in amounts as high as 1 gram each. Some doctors said that was an extraordinarily large amount to inhale. The first person developed a cough and shortness of breath but got better in a week.[The Washington Post articles cited, below, say, the cough lasted nine days.] Dr. Togias did not report those symptoms, deciding that the volunteer had caught a cold or that her symptoms were caused by the acidity of the hexamethonium solution. He altered the chemical to make it less acidic and gave it to a second volunteer, who had no adverse effects. [Apparently, a change in protocol, which was not reported, nor was the first person's reaction, which was not an anticipated.]

On May 4, he gave the chemical to Ms. Roche.
She began feeling ill the day after she took the drug. A few days later she was admitted to the hospital, the air sacs of her lungs collapsing. Her lungs failed and she died on June 2, after weeks in an intensive care unit, tethered to a respirator. A Hopkins committee investigating the death reported last week that the hexamethonium was probably what killed her. And it found reports in the medical literature that Dr. Togias had apparently missed, indicating that the chemical might injure the lungs....

[Note: This chemical was once used as a medication for blood pressure, but was taken off the market many years ago because of its side effects, when better alternatives were developed. According to Susan Levine, of the Washington Post, 07/17/01, Dr. Togias found safety studies on this drug done in the 1980s, but these involved only 20 subjects, and, apparently, he did not locate studies from the 1950s, which suggested pulmonary problems might occur with hexamethonium. - see http://www.washingtonpost.com/wp-dyn/articles/A6391-2001Jul16.html].

A substantial part is cited here. Material in brackets represents comments added by Sally Hobson. The information on this webpage is intended for non-commercial use only

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