Hopkins officials take blame for death

BALTIMORE, Maryland (CNN) -- Officials at the Johns Hopkins Medical Institution said Monday they aren't certain what caused the death of 24-year-old Ellen Roche, but they believe it was related to the drug she inhaled as a healthy volunteer in an asthma study.

Dr. Edward Miller, CEO of Johns Hopkins Medicine, told reporters, "We accept full institutional responsibility for her death."

On May 4, Roche inhaled approximately one gram of hexamethonium, a drug which constricts airways. She developed a dry cough May 5, flu-like symptoms May 7, and shortness of breath and a fever of 101-degrees May 9.

She died June 2 from multi-organ failure brought on by lung damage.

The Hopkins researchers were using the drug to study why irritants trigger asthma in some healthy people and not in others.

She was the third volunteer to participate in the study. The first volunteer developed a dry cough after inhaling the drug and the second had no side effects.

The internal investigation raised several red flags.

First, the cough developed by the first volunteer was never reported to Hopkins' institution review board, which oversees tests involving human subjects. Dr. Alkis Togias, the study's lead researcher, said he did not consider the cough serious enough to merit reporting, and wasn't sure it was related to the drug. The woman got better without treatment and there was a cold going around the hospital campus at that time, he said.

Second, the institutional review board was unaware studies carried out in the 1950s and 1960s -- when hexamethonium was used to treat blood pressure -- had shown it was associated with lung damage. But the studies were carried out in sick patients who had been taking the drug for at least a month.

"There really wasn't anything in the literature that would suggest that inhaled hexamethonium in a single dose would produce pulmonary toxicity of any kind, much less severe toxicity and death," said Dr. Lewis Becker Chair of the Johns Hopkins Joint Committee on Clinical Investigation.

Third, the clinicians departed from the approved protocol when they added sodium bicarbonate to the hexamethonium. It was added to make the patients more comfortable, but its addition was not approved by the institutional review board.

Johns Hopkins officials say they are taking steps to prevent this from happening again, including:

- The creation of a third institutional review board to handle the review of the large number of studies and increase expertise available for analysis of submitted protocols.

-An increase in the number of random quality control checks of ongoing research protocols to see how well they ensure safety and adhere to best practices.

- Initiation of an intensive review of the institutional review board processes by an external audit firm.

The Hopkins investigators are waiting on the results of an external review. For now, all of Togias' research projects have been placed on hold.