Asthma study patient who died worked at Hopkins lab|
By Tom Pelton, Jonathan Bor and Gary Cohn
Originally published June 17, 2001
The woman who died after inhaling a drug in an experiment at the Johns Hopkins School of Medicine was a 24-year-old lab technician who worked for the university's asthma center, which conducted the study.
Ellen M. Roche of Reisterstown, whom friends described as a bubbly, vivacious person who loved horses and had just bought her first house, was to have been paid $365 at the completion of the experiment, according to interviews and documents.
"She was perfectly healthy and a wonderful person. It's just a tragedy to have something like this happen. She volunteered for the study to try to help others," said Charles Noel, a retired railroad supervisor from Reisterstown and longtime family friend.
Roche died June 2 at the Johns Hopkins Bayview Medical Center, about a month after taking part in an experiment designed to help doctors understand a healthy person's natural defenses against asthma.
She developed a cough and flu-like symptoms a day after the test and was admitted to the hospital after X-rays showed a lung inflammation.
Roche's death was the first time in more than a decade that a research subject died at Hopkins from complications directly related to an experiment - not from an underlying illness.
The death was announced Wednesday by the medical school in a sparsely worded statement that did not identify the volunteer. The Office for Human Research Protections, which oversees the safety of federally funded research studies, launched an investigation the next day.
Yesterday, Hopkins released a detailed description of the study and a consent form shown to volunteers before they were accepted.
In the consent form, doctors warned of possible side effects including a cough, dizziness and a tight chest - but nothing life-threatening.
Medications and fluids would be given, they said, to reverse any side effects. A doctor would be present to treat the patient if problems arose.
Researchers planned to recruit 10 people, some of them staff at the Johns Hopkins Hospital and the Bayview Medical Center. While it is a common practice for medical centers to recruit employees and students as research subjects, some ethicists say it raises questions about whether they feel subtle pressure to volunteer.
In their description of the study, researchers said they were attempting to discover the natural mechanisms that protect healthy people from having asthma attacks. Asthma, which strikes 10 million Americans, is a disease in which the airways close down when patients breathe allergens, irritants or other substances.
The experiment, funded by the National Institutes of Health, was directed by Dr. Alkis Togias. It was part of a larger body of research overseen by Dr. Solbert Permutt.
In studies that began several years ago, Hopkins scientists discovered that healthy airways tend to close down, too. But people compensate by taking deep breaths that stretch the airways and cause them to reopen.
The experiment in which Roche died was designed to identify the exact reflex - the neurological pathway - that causes this response.
Volunteers were told that they would visit the center seven to nine times. During the first four visits, they would inhale a drug, methacholine, to induce "a mild asthma attack" that would produce a tight chest, some coughing and mild shortness of breath, according to the consent form.
"These go away on their own within a short period of time," the form says. "If you do not want to wait until the symptoms go away on their own, a lung spray will be given to you which will take the symptoms away within a few minutes."
Experts outside Hopkins said methacholine is commonly used in research and in clinical settings and is regarded as safe.
During the fifth visit, volunteers would be asked to take deep breaths before or after inhaling the drug, the form says. This would help doctors observe whether the breaths prevented the mild attack by opening the airways.
Roche apparently died in a subsequent phase of testing that began with the sixth visit. Some volunteers would take another drug - hexamethonium - before taking methacholine and breathing deeply.
Doctors had theorized that that drug would counteract the beneficial effects of deep breathing. If doctors could interfere with the body's defenses, they might better understand how those worked.
Hexamethonium could have side effects, the volunteers were warned. It could reduce blood pressure and make them feel dizzy when they stood up.
As a safeguard, volunteers would be hooked up to a heart monitor and have their blood pressure monitored. Doctors could also provide fluids through an intravenous tube if blood pressure sank dangerously low, the form said.
What sparked Roche's medical crisis remains a mystery. One question is whether the drug was to blame. Once widely given to treat high blood pressure and to reduce bleeding during surgery, hexamethonium has not been used clinically for many years.
A hypertension expert who was unfamiliar with the Hopkins case said the drug's benefits -and its side effects - were almost always short-lived.
"Whatever happened to the patient was probably unrelated," said Dr. Edward D. Frolich, a hypertension expert at the Ochsner Institute in New Orleans.
In letters sent to federal oversight agencies, Hopkins indicated that it was analyzing the hexamethonium for possible contamination but was considering other causes, too. Scientists were studying a spirometer - a device that measures lung capacity - and other medical equipment as possible sources of infection.
Doctors performed an autopsy and were testing tissues to see whether Roche had developed an infection.
"There are no results at this time," said Joann Rodgers, a Hopkins spokeswoman. "We are cooperating with these agencies and trying to find out [what happened]. That process is continuing."
The safety of medical experiments has become a matter of public concern since the death two years ago of an 18-year-old man in a gene therapy trial at the University of Pennsylvania. That incident provoked calls for closer government monitoring of experiments ands better self-policing by medical centers.
Roche was one of seven children and stepchildren of a photographer, Bernard J. Roche Jr., and his wife, Carolyn, who have lived for years in a wood-frame home in Reisterstown that also serves as the photo business.
More than almost anything, Ellen Roche took great joy in caring for animals, friends said. She owned two horses, keeping one - called Clown - for a while in her family's back yard. She had enjoyed the Carroll County Rabbit Club and 4-H Club, according to an obituary in the Carroll County Times.
"She was a very nice girl, very outgoing, very helpful to others - and, boy, did she love her horses," said Betty Noel, a longtime family friend.
Ellen Roche graduated from Franklin High School in 1994 and Frostburg State University in 1998. She worked in the labs at the Asthma and Allergy Center at Hopkins' Bayview Campus. And she was proud to have bought her own place last June - a $83,000 townhouse not far from her parents' Reisterstown home, friends said.
"She was such a healthy person - that's what really gets me," said Betty Noel. "When I heard she was hospitalized, I just couldn't believe it."
Hundreds of people packed her funeral June 7 at the Eckhardt Funeral Chapel on Reisterstown Road.
Craig Schoenfeld, an attorney who said he is acting as the Roche family's spokesman, said the family did not want to comment. "They are trying to grieve. When the time comes and they want to speak, they will speak," Schoenfeld said. "But right now they are just trying to grieve."
The Hopkins study was suspended after Roche became ill. She was the third volunteer to be tested, according to documents filed with federal agencies.
Hopkins employees say researchers often post fliers around the Bayview center cafeteria and elsewhere seeking recruits - fellow doctors, lab techs, students - for the center's experiments. That's because it's easier to find subjects on their East Baltimore campus than to find volunteers in the community.
Recruiting within an institution is common at academic medical centers, said Ruth Faden, director of the Hopkins bioethics institute. She said, however, that it is important to ensure that participation is voluntary.
"You certainly want to guard against a situation in which someone who is an underling feels manipulated or coerced," Faden said. The practice at Hopkins is to post notices and advertise rather than directly ask employees to participate.
Outside Hopkins, ethicists were divided on whether academic medical centers should recruit employees for studies.
George Annas, chairman of the health law department at Boston University's School of Public Health, said he didn't see anything wrong with allowing an institution's employees to serve as research subjects - provided they feel free to refuse.
But Dr. Michael Grodin, director of medical ethics at that university's School of Medicine, disagreed. He said employees might be reluctant to say no, fearing they would not be seen as team players.
"The fact that it's convenient doesn't justify it," Grodin said. "The bottom line is you shouldn't use people employed by the institution doing the research because there's potential conflict and coercion."
Sun staff writer Michael Stroh contributed to this article.
Copyright © 2001, The Baltimore Sun