SSKRP ATTORNEYS IN THE NEWS

Safety among medical testing under scrutiny

By Janette Neuwahl, Daily Northwestern - Northwestern U.

03/2002

EVANSTON, Ill. (U-WIRE) Ellen Roche, a previously healthy 24-year-old, died in June when her lungs and kidneys failed during an asthma experiment at Johns Hopkins University.

Jesse Gelsinger, 18, died in September 1999 when a gene therapy experiment at the University of Pennsylvania triggered an overwhelming response from his immune system.

Failure to protect volunteer subjects at Duke University and the University of Rochester has led to federal scrutiny of the research programs, and the shutdown of testing facilities at Duke in 1999.

In response to these incidents, universities nationwide including Northwestern are focusing on how they protect research subjects, said Lydia Villa-Komaroff, NU's vice president for research.

"Every time something happened (nationally), we would sit down to make sure the way we did things would minimize the chance that this would happen," Vil la-Komaroff said.

At a December conference, five NU administrators joined 1,500 others to discuss safety during experiments. This week the National Institutes of Health is meeting to discuss a similar topic. Efforts to improve protection at NU have included hiring more staff for the Office of Protection of Research Subjects and expanding the number of its Institutional Review Boards, which approve or reject applications for every study conducted at NU. The Medical School also has a research subject advocacy program.

But of the thousands of NU's research studies, none has come close to resulting in fatalities, OPRS Director Carol Nielsen said. And a 1999 audit by the Food and Drug Administration did not uncover any policy violations. Still, Villa-Komaroff conceded the difficulty in monitoring NU's 2,300 studies at its six major facilities.

"We have found instances where people didn't keep the right records or they didn't tell the OPRS when they made a change in the study, and we made sure they corrected this," she said.

Many studies are unnecessary, leading to an overburdened staff in protection offices, said Alan Milstein, a lawyer who represented the Gelsingers and who specializes in clinical research litigation.

"There are too many experiments going on and too many that are trivial, it's simply not true that every experiment is essential to the advancement of science," Milstein said.

A research assistant scribbled notes furiously recently as Robert Thonander, an 85-year-old retired lawyer and Evanston resident, paced back and forth down a hallway at NU's General Clinical Research Center. After the walking exercise, the assistant explained Thonander's progress in the 740-member study he began in 1998.

"They were very thorough in explaining the study I was participating in," said Thonander, a 1940 graduate of what NU then called the College of Liberal Arts.

"As with any research, I hope that something will come out of it that will help somebody. But it may produce nothing."

The study, one of 70 taking place at the center, concerns peripheral arterial disorder, which causes leg pain in many senior citizens. As an alumnus, Thonander said he wanted to participate to help NU's research efforts.

Other research subjects at NU include the Introduction to Psychology class, where students must sign up for 10 hours of experiments or choose to write a paper. All subjects have to sign a consent form, no matter how minimally invasive the testing.

"My experience was incredibly boring because you sit by yourself in front of a computer for an hour," said Weinberg freshman Josh Harmon. "Before the testing they would give you a copy and take a (signed) copy of the consent form that was standard procedure."

But whatever the experiment, Milstein said subjects should not accept risks they don't fully understand. Volunteers for studies often receive monetary compensation from the research grant; other times they simply receive free medical testing or health insurance.
"The only reason why a subject should be in a research project is for altruistic reasons," Milstein said. "Nobody should be a subject for the money and if you are, it's a problem."

At NU, when researchers submit their applications for experiments to review boards, they also must describe their recruiting methods. Many of NU's volunteers are recruited through advertising or doctor recommendations, Villa-Komaroff said.

Roche was actually an employee at Johns Hopkins when she took part in the experiment because she "felt she had to be loyal to her job," Milstein said. Roche died after inhaling hexamethonium, which led to the progressive failure of her lungs and kidneys. An investigation found that the doctor conducting the study failed both to acquire the FDA's approval for using hexamethonium and to inform the group of volunteers that they would be inhaling an unapproved drug.

University President Henry Bienen said he has spoken with the president of Johns Hopkins about the death and said that the research facility's guidelines were quite strict, but that mistakes are inevitable.

"Since you're dealing with life and death, you try to have the most serious and strictest policies, though there's always human error," Bienen said. "There's human error in the operating room. There's human error in data entering. ... You do the best you can."

"Milstein said a lack of supervision from institutional review boards at research facilities across the country can also explain mistakes in testing during the past few years.

"While the IRB members may have good hearts and good motives, they can't possibly monitor all the studies being done," Milstein said. "The repeating problem is the IRBs are overwhelmed with work, and this is the body to protect subjects."

As far as Northwestern's protection methods, Milstein said the amount of review boards is cause for concern. With four review boards and 2,300 studies, he wondered how NU could possibly monitor all of them when the boards meet only once a month.

To satisfy federal regulations, the boards must have five members, although most of NU's four panels have about 15. Three of the boards focus on medical research downtown, while one reviews behavioral science research, mostly in Evanston.

Research oversight also has expanded since Villa-Komaroff joined NU six years ago. The OPRS staff has increased from three to 11, and the number of review boards has doubled from two to four in the last three years.

But staffing levels aren't the best indication of how much protection research subjects receive, Nielsen said.

"It isn't a measure of the amount of people but the amount of time dedicated to a project," Nielsen said. "There's no correlation between the number of people and the consideration for each trial."

Although administrators say the hirings are unrelated to the mishaps at other universities, the heightened level of concern is apparent.

"NU is constantly checking to try to be sure that we are doing a good job of ensuring the safety of people who have volunteered to be subjects," Villa-Komaroff said. "We are a part of national efforts to re-evaluate the way that universities and medical schools protect people."

Medical School Prof. Sigmund Weitzman, hired as part of the OPRS' expansion in September, said the increases were necessary because of the greater number of applications for experiments involving people.

"They are doing twice as many clinical trials as they did five years ago, so if the trend continues, we may need to increase our number of IRB panels," Weitzman said. "Right now we have enough but we're growing rapidly."

Villa-Komaroff said the university might add a fifth review board in the spring to handle the inundation of protocols the OPRS receives.

Violations of subjects' rights often are hasty results from researchers' dreams of recognition and riches, Milstein said.

"There's a lot of pressure among professors and researchers (at universities especially) because they want to bring in grant money for tenure," Milstein said. "These kinds of pressures, such as the desire for fame and the need for recognition among their peers, can all work to shift the focus away from the protection of research subjects."

To help combat the economic pressures, NU began a conflict-of-interest policy in September against researchers having any financial stake in the organization or company that funds their study, Villa-Komaroff said. NU's two main medical research sponsors are drug companies and federal agencies.

"I know of one faculty member who gave up his stock so that he could do the trial," Villa-Komaroff said. "The conflict-of-interest policy is an issue which is now a general recommendation for research facilities nationally."

Despite the increasing amount of precautions, both Milstein and Gelsinger's father, Paul Gelsinger, say they would probably not volunteer themselves for research.

"The motivating forces that are out there right now would make me very leery of participating," Gelsinger said.