Trials and Errors: a Hospital Takes a Hit
Human research is halted at Johns Hopkins
Papering the bulletin boards at the Johns Hopkins Bayview Medical Center, dozens of colorful fliers beckon the healthy and the sick. They are soliciting volunteers for the scores of research studies that have made this Baltimore institution among the highest ranked in U.S. News & World Report and a top recipient of federal research dollars--over $300 million last year. One healthy person who answered the call was 24-year-old lab technician Ellen Roche. Whether she was attracted by the $365 stipend or the chance to advance science is not known. What is clear is that her participation in the asthma experiment killed her. Roche lapsed into a coma after taking a single dose of a drug that researchers had failed to tell her carried serious medical risks.
Now that mistake--among others--has temporarily cost Johns Hopkins the privilege of conducting any human experiments funded by the government. Last week, the federal Office for Human Research Protections suspended almost all of the university's studies involving human subjects after investigators found numerous safety problems. Specifically, OHRP found Hopkins's oversight committees--called institutional review boards, or IRBs--had failed to adequately inform patients of dangers.
Shutdowns. The troubles at Hopkins are only the latest in a series of setbacks to clinical trials on human subjects. Two years ago, an 18-year-old man died while participating in a gene therapy study at the University of Pennsylvania, causing a temporary halt to some trials there. That same year, the government temporarily shut down studies at Duke University. "There is hardly a research institution out there," says Paul Fishman, the former IRB chairman of the University of Maryland Medical Center in Baltimore, "that could not find ways to do it better."
Hopkins officials called the suspension "unwarranted, unnecessary, paralyzing, and precipitous." Yet letters obtained by U.S. News show that the Roche case was not the first to raise regulatory concerns. In a letter dated March 3, 1998, Diane Aiken of what was then the Office for Protection from Research Risks found that participants in cancer clinical trials at Hopkins signed consent forms that "lacked toxicity and treatment information." She also said the review board "failed to conduct continuing review in a timely fashion." An internal investigation later determined that several risk statements had been inadvertently omitted to make the consent form more understandable.
Hopkins has since made its forms more specific, but Ellen Roche never signed a new form. She also was not told that one of the drugs used in the trial, hexamethonium, was not approved by the Food and Drug Administration. Nor was she informed, investigators say, that the study could cause her serious harm or death. Twenty-four hours after inhaling the hexamethonium, Roche developed a cough and, later, a fever. An internal report said the director of the project failed to report that a previous volunteer had developed a persistent cough as well.
Although Hopkins has assumed responsibility for Roche's death, officials say the tragedy highlights confusing regulations on when researchers must seek government permission to test drugs in people. The FDA must approve all pharmaceutical research intended to find new therapies, yet it makes different demands of academic institutions that embark on scientific studies not aimed at treatment.
To resume its trials, OHRP says Hopkins must develop "corrective action plans," including establishing more review boards and better educating staff about regulatory requirements.
This story appears in the July 30, 2001 print edition of U.S. News & World Report.