Drug trials under scrutiny

People suffering from life-threatening diseases turn to experimental treatments, which can carry special risks

By CLAIRE HUGHES, Staff writer

First published: Sunday, March 30, 2003 Albany Times Union

After removal of Lynn Gasorowski's breast and lymph nodes failed to rid her of cancer, doctors wanted to continue attacking the disease aggressively.

Albany oncologist Dr. Michael Kolodziej Gasorowski participate in an experimental study in which she would receive three drugs not usually taken together. She would get four treatments in under four months, half the time of the standard regimen.

Gasorowski agreed to give it a try. But after the third treatment, she was weak, incoherent and dehydrated. "I'm saying, 'This is it, let me die,' " Gasorowski recalled.

Kolodziej told her that she could back out of the study, though he encouraged her to keep going. She did.

Four years later, the 46-year-old Colonie woman remains cancer-free and a believer of clinical drug trials -- experimental studies in which patients take new, unapproved medicines or new combinations of approved medicines. But as companies try to push more drugs to market, the studies have come under increased scrutiny after a series of mishaps.

Last month, the news broke that federal authorities were investigating whether two former researchers at Stratton Veterans Affairs Medical Center Hospital in Albany improperly enrolled patients in drug trials they weren't eligible for. The researchers, Dr. James Holland of Voorheesville and Paul H. Kornak of Clifton Park, could face manslaughter charges if found responsible for speeding as many as five patients' deaths.

This comes after the Institute of Medicine in Washington, D.C., last fall recommended broader federal oversight of research involving patients. The report was commissioned after the death of an 18-year-old during a gene-therapy study at the University at Pennsylvania. In 2001, the prestigious Johns Hopkins University in Baltimore was ordered to halt research on patients temporarily after the death of a healthy 24-year-old woman in an asthma study.

The Albany case has sparked a federal review of research throughout the entire VA medical system, especially because Kornak had his medical license revoked in three states before being hired at the VA.

Still, local researchers and hospital managers outside the VA said the situation should not stop people from participating in drug trials. The studies aid the development of cures for deadly and debilitating diseases and can provide patients access to effective drugs years before they're on the market.

"Any rogue investigator could bypass the informed consent process and recruit patients" who didn't belong in the study, said Lee Van Voris, chief medical officer at St. Peter's Hospital in Albany.

Consumer advocates and an attorney representing the families of deceased drug trial participants agreed that Kornak's background makes the Albany case unusual. But they said a more common problem may have contributed -- lax oversight. They cautioned people to evaluate risks carefully before jumping in.

The problem, said Philadelphia attorney Alan Milstein, was that oversight bodies "failed in monitoring and supervising what was going on and ultimately in protecting the human subjects."

Milstein has filed a class-action lawsuit against Kornak and Holland, claiming the researchers violated well-established medical standards and patients rights.

Hundreds of people in the Capital Region currently are in studies to test drugs. St. Peter's, Albany Medical Center, Ellis Hospital and Glens Falls Hospital offer studies, as do some doctors' offices.

To participate in drug trials, patients must meet strict medical criteria. They also must be informed of risks and be allowed to back out at any time.

No one involved in the investigation of Holland and Kornak has offered a possible motive for their alleged falsification of patient records to enroll study participants.

In general, experts said financial incentives can tempt researchers to seek more patients for their studies. Depending on the source, drug companies can pay researchers $1,000 to $2,500 per patient enrolled in a trial.

"The money is enormous, and it is poisoning the process," Milstein said.

Local researchers dispute the claim that study work is especially lucrative. They offer drug trials mainly, they said, because the studies provide treatments patients could not otherwise get.

"I look at clinical trials as doing the ultimate right thing for our patients," Kolodziej said. "There are not oncology practices getting rich on clinical research."

At Albany Medical Center, which participates in about 100 drug studies annually, clinical trials contracts brought in $6.5 million last year, said Dr. Vincent Verdile, dean of the center's medical college. But those contracts just covered the institution's costs, including researchers' salaries and medical tests for participants.

"It's an absolute wash," Verdile said.

Researchers who work at hospitals or universities have no direct financial incentive to enroll patients because the institution receives the fees.

Still, for the institution, a base of research can attract grant dollars and lure talented scientists, Verdile said. And bringing money to an institution helps a researcher's career, said John Kaplan, a professor at Albany Med's Center for Medical Ethics, Education and Research.

"Any given person working in an institution is better off if they bring in money than if not, generally," Kaplan said.

At the Stratton VA, Holland and Kornak's patients were terminally ill with cancer. Some, like Donald J. Lifgren of Schenevus, faced few treatment options.

"When somebody thinks they're going to die, they'll grasp at any straw to stay alive," said his widow, Nancy R. Lifgren.

Because patients with limited options can easily be swayed, drug trials can present ethical questions even with the most sincere researchers, said Arthur Levin of the New York City-based Center for Medical Consumers.

"The more vulnerable the patient population, the more care there has to be that as little coercion or no coercion occurs, that people are making these choices in a considered way and not being railroaded with false hope, which the researcher may honestly believe," Levin said.

At Stratton, the VA's Office of Research Compliance and Assessment was charged with monitoring the drug studies. Hospitals where research is done also have internal oversight panels, called institutional review boards.

Members of boards at other hospitals said they are compulsive about overseeing research at their institutions and were surprised to read reports that it took the VA's oversight bodies nearly a year to halt studies after a drug company noticed discrepancies in records.

"Any institutional review board worth its salt is going to find out about that pretty quickly," Van Voris said.

VA officials have repeatedly declined comment on their research programs since the federal probe was disclosed.

The IOM's fall report stated the internal review boards have become overburdened with the rise in number of drug trials. The report called for the formation of participant protection programs to take over some of their functions.

Still, drug studies are not inherently bad -- just risky, Levin said. What's important is that participants have all the relevant data to make sound decisions, he said.

"If you're very sick and nothing is working, you may be willing to take more risk," Levin said.

After her husband's experience at Stratton, there's nothing that would get Lifgren into a drug trial. "I don't trust them now," she said.

Barbara Waring, on the other hand, will likely continue to participate. The 58-year-old Duanesburg resident was diagnosed in 1995 with Parkinson's disease, a progressive movement disorder marked by tremors.

She got involved in her first drug trial with Dr. Stewart Factor of Albany Med in 1996 and ended up on a drug that helped her symptoms. She participated in a second study that required lots of blood tests, but had no direct benefit to her.

What she wants, she said, is to help find treatments for Parkinson's that will allow patients to live better with the disease early on -- when they can still enjoy themselves.

"I feel like somebody has to do these," she said.

EVALUATE FACTORS:

The decision to participate in a drug trial comes down to evaluating a number of factors:

How sick are you?

Are there other treatments for your disease that are working?

What's the prognosis for your illness? That is, how long do you have to live if you don't try a new treatment?

How likely is it that the treatment will work, based on previous studies?

What phase is the drug development in? Phase II trials usually are done on healthy people to test the safety of a drug and side effects are less predictable. Phase III trials involve patients with diseases the drug is intended to treat, and there is more research to base expectations on.

Are your questions to the doctor and institution being answered promptly and honestly?

Sources: Art Levin, Center for Medical Consumers; Dr. Stewart Factor