Sunday, May 30, 1999
Human drug tests: Profits vs. ethics?
BY ANNE MICHAUD and TIM BONFIELD
The Cincinnati Enquirer
To understand the tremendous stakes involved in treating mental illness, consider this: Sales of the anti-depressant Prozac exceed $1 million a day.
The hunt for the next, better Prozac is turning psychiatric research into a booming industry. The National Institutes of Health is poised to double its research budget. Pharmaceutical company studies have quadrupled in a decade, from a handful of drugs in clinical trials, to between 40 and 50 in development today.
Researchers say drug development is nothing less than a revolution in treating mental illness. But getting those drugs to market requires human testing, and that has raised ethical questions about how volunteers are being treated.
The University of Cincinnati is at ground zero in a national debate over the proper treatment of patients involved in psychiatric research. UC is among several prominent medical centers facing federal inves tigations of research methods. Meanwhile, lobbyists are pushing the White House and Capitol Hill for even tougher regulations to protect patients.
The common thread in this conflict over research needs and patient rights: money.
“What I'm worried about is, there's a push to get these drugs on the market, and they're looking for bodies,” said Jim Coleman, coordinator of Recovery Initiative, a Walnut Hills resource center for the mentally ill.
UC has reformed some of its practices based on the federal investigation and critics' complaints, eliminating the most controversial type of research, known as “challenge” studies. No such studies were under way last month when UC made the announcement.
By contrast, another contro versial research method, placebo studies, makes up 40 percent of the university's current studies, according to documents obtained through an open records request. UC has made no plans to eliminate placebo research — which by design results in some test subjects receiving no care for their illness.
The UC psychiatry department, including the affiliated VA Medical Center and Children's Hospital Medical Center, conducts about $5 million in research on mental illness each year, said Dr. Randy Hillard, department chairman. The department's goal is to double that figure over the next five years.
The department is running 53 studies involving human subjects, eight of which are funded by federal health agencies. The other 45 are sponsored by 16 different drug manufacturers.
UC would not release financial details of individual corporate-sponsored studies, claiming such information would reveal clients' trade secrets.
But budget documents give an overall picture. Drug company “sponsored programs” at UC's psychiatry department have grown nearly 30 percent in three years, from $2.5 million in 1997-98 to $3.25 million in 1999-2000.
The increasing financial support for psychiatric research may improve the lives of millions. Clinical depression affects more than 17 million Americans; schizophrenia another 2-3 million.
Before the pharmaceutical breakthroughs of the 1990s (such as widespread sales of Prozac), only half of psychiatry's patients responded well to treatment, Dr. Hillard estimated. Now, about 70 percent do.
“It has been excellent progress, but there's a lot of room for improvement,” he said.
New medications — based on research into how the brain works, advances in genetic science and other factors — eventually will transform care for depression, bi-polar disease, drug addiction, even obesity, he said.
Among the UC's most exciting studies: early efforts to develop a vaccine to prevent people from craving cocaine.
“This is one of those things that five years ago I would have put in the same category with time travel and anti-gravity boots,” Dr. Hillard said.
But he denies university researchers have cut corners on ethics to achieve such advances.
“The universities, for all of their faults, do have quite a bit of public accountability,” Dr. Hillard said.
Even as scientists emphasize the room to improve treatments for mental illness, advocates say there's even more room to improve how the mentally ill are treated. Too often in this hunt for the next great medication, the most vulnerable people end up in research studies: the poor, undereducated, elderly and mentally ill, said Adil Shamoo, a professor of biochemistry at the University of Maryland and a leading critic of human subject research.
“The next frontier of medicine is modification of behavior, so there is tremendous pressure to recruit more and more human subjects,” Dr. Shamoo said. “Of course, it's very profitable. The researchers, that's how they make a living and become famous.”
The definitions of acceptable human research are changing.
Under scrutiny from the federal government and Cincinnati-area mental-health activists, UC said last month it will suspend “challenge” studies, which use chemicals to induce psychosis. The aim was to study biochemical roots of psychosis or to test preventive treatments.
A former UC research participant, Shalmah Prince, says her 1983 experience in a challenge study changed her identity and worsened her illness. Ms. Prince suffers from manic depression.
When UC announced it was suspending challenge studies, however, there were no active studies of that type, nor plans to undertake any. Actual money is at stake in the placebo debate.
Unlike the relatively rare challenge studies, millions of dollars at UC are linked to placebo studies. According to documents obtained by the Enquirer, 21 of the 53 active psychiatric studies — nearly 40 percent — involve using a placebo.
Patricia Reynolds, of Carthage, was admitted to University Hospital in May 1998 and approached to volunteer for a placebo study. She was having an episode of mixed mania, she said, and was so divorced from reality she believed she was an angel.
“I left, feeling they were more interested in using me as a guinea pig than in treating me,” she said. Later the same day, she tried to kill herself.
Dr. Hillard has said the hospital had no right to keep her against her will. He argued that patients can make decisions about their own care, even when they are delusional and hallucinating — hallmarks of psychosis.
The FDA and the National Institute of Mental Health are conducting a nationwide review of the use of placebo studies.
The ethical concern: Should some patients, in the interest of advancing science, be allowed to suffer harm from their untreated illness while taking a sugar pill?
Leonard Glantz, a professor of health law at Boston University School of Public Health, said it's a question of loyalty between patient and doctor.
“The question is, how can a doctor be loyal to you and suggest you not take a treatment that would otherwise be helpful to you because he wants to derive something else?” he said.
Researchers say placebo studies are crucial to science, and beyond that, required by the government to bring a new drug to market.
“There would be statistical ways that we could use fewer placebo patients in studies,” Dr. Hillard said, “But I don't know whether we could eliminate them entirely, as long as the FDA is requiring that you show the new drug is superior to placebos.”
One reason for the use of sugar pills is to control for the so-called placebo effect, a well-known phenomenon in medical research, and especially common in psychiatric care. Over the years, doctors have learned that some people get better even if they take nothing more than a sugar pill.
Patient advocates say the risks of winding up with a placebo are seldom explained clearly enough. To reduce risks for study participants, patient advocates support comparing current drugs with new drugs, known as head-to-head trials.
But head-to-head tests are much more expensive than placebo studies, Dr. Hillard said. It can take as few as 1,000 patients to prove that a new drug works better than nothing. It may take 10,000 patients to show that a new drug works better than the existing therapy.
“We can probably satisfy the FDA without using placebo studies if we're willing to do about 10 times as many subjects,” Dr. Hillard said. “But I think that society overall thinks the drugs are too expensive already.”
Drugs for psychosis have big impact
Can we learn anything from opposite sex?
Who's patrolling on the Ohio?
Human drug tests: Profits vs. ethics?
Teen killed, diploma in sight
Bus money hinges on state assist
Children's insurance program lauded
Pick your battlefield
N.KY. MEMORIAL DAY EVENTS
Crowds savor Taste of Cincinnati
McGuffey house mysteries
Peacecamp helps kids defuse anger
Police following leads on Love
When questions get tough, politicians seek shelter
Knip's Eye View
Treasures buried in beloved book bags
African-American dance exhibit educates, gets your spirit moving
GET TO IT
Orchestra marries score to 1925 'Phantom' flick
Paper in meetings leaves out workers who read Braille
Small race may get big interest
Class achieves pride and expectation
Construction lands at airport
Dogs raised to win
First police fatality puts Indiana county in mourning
Having impact before disaster
Internet investment club a fraud, suit says
Man accused of abusing dogs
Many communities restrict sales
Patton: Lack of a race telling
Pools try to lure lifeguards
S. Lebanon ladder truck to aid Ky. fire department
Seven of state's Vietnam Vet chapters in danger of folding
TRISTATE DIGEST
