In the first detailed account of how it is responding to the death of a research subject, the Johns Hopkins School of Medicine revealed yesterday that it has convened a panel of Hopkins physicians and outside experts to determine what might have caused the tragedy.
The panel will examine substances used in the asthma experiment, the consent form signed by volunteers and the actions of the internal Hopkins review board that approved the study, according to a statement posted on a Hopkins Web site. It will try to find out "whether there is a way to establish the most likely cause of the volunteer's death in light of the best clinical evidence," the institution said.
A final report will be submitted to federal authorities by July 13, Hopkins said.
Ellen Roche, a 24-year-old lab technician, died June 2 at the Johns Hopkins Bayview Medical Center, about a month after inhaling a chemical in an experiment that was designed to help doctors understand how healthy lungs protect against asthma attacks. The federally funded study was performed at the Johns Hopkins Asthma and Allergy Center, where Roche worked.
A preliminary investigation has turned up "some problems" relating to how closely scientists adhered to procedures approved by the Hopkins Institutional Review Board, the internal committee that must approve and monitor all experiments involving human subjects.
In the only example mentioned, Hopkins said the scientists changed the manner in which they prepared the chemical, hexamethonium, before it was given to volunteers.
In the proposal approved by the review board, scientists said they would dissolve the chemical in a saline solution that would then be inhaled by the volunteers. Instead, the principal investigator dissolved the chemical in buffered distilled water.
"While he believed this modification is consistent with past practices as reflected in the scientific literature and was intended to enhance the comfort of the patients, such modifications should have been presented to the IRB for approval," according to the Hopkins statement.
Although Hopkins did not name the scientist in its statement yesterday, internal documents list the principal investigator as Dr. Alkis Togias, an asthma researcher.
Hopkins did not indicate whether using buffered water rather than saline might have compromised patient safety, or whether it was merely a technical violation of the protocol.
Dr. Gary Smith, a professor at the University of Maryland School of Pharmacy, said yesterday that scientists commonly use either saline or distilled buffered water to prepare drugs and chemicals given to people.
"It sounds like a really minor thing, a procedural thing that shouldn't cause any harm," Smith said.
Both are used to produce a solution that has the same acidity as the body's fluids, preventing unwanted side effects, he said.
Buffered water contains small amounts of a chemical, such as phosphate, that causes the solution to be less acidic than pure water. Saline does much the same thing, he said.
In its statement yesterday, Hopkins indicated that it convened the panel after authorities conducting a preliminary investigation turned up irregularities including the way the chemical was prepared. Joann Rodgers, a Hopkins spokeswoman, said the panel was convened after Roche died, but she declined to say precisely when.
The panel will submit its final report to the federal Office for Human Research Protection. Hopkins is also in the process of naming an "independent outside group of experts" that will review the findings.
The independent group's report will be sent to government agencies, Johns Hopkins President William R. Brody and the university's board of trustees, Hopkins said.
Dr. Arthur Caplan, who heads the bioethics program at the University of Pennsylvania, said the steps by Hopkins in the wake of the tragedy are appropriate.
"That's pretty much what the standard would be for responding to this situation," Caplan said. "It's sort of going inside, going outside, reporting to the relevant groups and authorities. I think it's a reasonable and commendable approach."
The University of Pennsylvania took a similar approach after an 18-year-old volunteer died in a gene therapy experiment two years ago, Caplan said.