If you want to be a human guinea pig, there's a job for you in Baltimore.
Advertisements seeking healthy medical research volunteers appear in local newspapers, on fliers in college dormitories and on Web sites such as GPGP.net, which lists experiments worldwide.
The City Paper alone features four pages of ads involving studies on treatments for bird flu, dengue fever, West Nile virus, asthma, insomnia and other ailments. Many want healthy people willing to take experimental drugs in exchange for money -- in some cases, thousands of dollars.
Scientists say this is a legitimate avenue for seeking volunteers. Also, many volunteers sign up for altruistic reasons.
But a provocative new study by Johns Hopkins researchers suggests that the lure of substantial payments is particularly strong for the poor and uneducated. It found that low-income people were more likely to sign up for multiple experiments and volunteer for riskier studies. In fact, nearly a third of the respondents had joined in 10 or more trials.
Experts in medical ethics say the Hopkins study raises difficult questions about the way research is conducted. Scientists don't know much about the long-term health effects of repeatedly volunteering for such studies. Nor do they have a definitive way to determine if participants violate guidelines that prohibit joining more than one study at a time.
"That could pose a risk to the volunteers, and a risk to the science," said Nancy E. Kass, deputy director for public health at the Johns Hopkins Berman Institute of Bioethics and one of the study's authors.
The study -- a small one involving 60 volunteers, most of whom had participated in at least one study at Hopkins -- was published online last month in the journal Clinical Pharmacology & Therapeutics.
Medical researchers seeking healthy human subjects are usually conducting Phase I clinical trials of experimental drugs or devices. They are the first batch of human tests required to show the Food and Drug Administration that a new treatment is safe and effective.
In the United States, nearly 2,000 Phase 1 clinical trials are registered with the National Institutes of Health. Of those, 145 are located in Baltimore and currently recruiting volunteers.
At this early stage, scientists are trying to determine whether a treatment does any harm to otherwise healthy people -- not whether it actually works.
Typically, a small group of 20 to 80 volunteers takes a drug previously tested for safety only in animals. Researchers have attempted to predict side effects and safe dosages, but they can't be sure what will happen until people take the drug.
While most volunteers experience only mild side effects -- such as headache or nausea -- on rare occasions the experiments result in permanent injury or death.
Some experts also worry that scientists don't know enough about the long-term effects of repeated exposure to potentially toxic, experimental drugs. With no state or national registries for volunteers, there's no guarantee that subjects will wait long enough between trials. Nor can researchers spot patients who join multiple trials simultaneously.
"A lot of volunteers we talked to were crossing state lines to participate in studies," Kass said.
One volunteer who has made a small living from studies in recent years said he often meets participants from out of state. "It's a lot of money," said the Baltimore man, who requested anonymity because he worries that he will be excluded from future studies.
He said he is enrolled in a drug study that pays more than $2,000. In the past, similar sums have prompted him to wait less than a day between studies, and to join two experiments at the same time.
"I was doing one study at Hopkins, on the weekends," he said, "and then I would go to [a different one] Monday through Friday. They ask you if you've been in another trial in the last 30 days, but, of course, we would say, 'No.'"
He said he worries about the possible toll on his health but noted that he made roughly $10,000 in study payments. "I'll probably go back to school once I've done enough of these," he said. "There's a price to be paid for everything."
Exactly how much risk volunteers take on is difficult, if not impossible, to determine. Some experience no side effects, while others might develop headaches, vomiting and diarrhea. In rare cases, the outcomes are more severe.
One highly publicized case in Baltimore was the 2001 death of Ellen Roche, a 24-year-old lab technician at the Johns Hopkins Bayview Medical Center who suffered lung damage and multiple organ failure after taking an experimental asthma drug.
The FDA later ruled that the Hopkins researcher leading the study had failed to get proper federal approval and had not fully disclosed the health risks to the volunteers.
Another case made headlines in March 2006, when six men suffered multiple organ failure during a drug trial at Northwick Park Hospital in London.
The men were paid nearly $4,000 to take an experimental anti-inflammatory drug called TGN1412 at a clinic run by Paraxel, a Boston-based company that also manages clinical trials at Baltimore's Harbor Hospital.
British government drug regulators ruled that the incident was the result of an "unexpected biologic effect."
Despite the publicity over these and other clinical trial problems, the latest Johns Hopkins survey suggests that some volunteers are largely unaware of the dangers involved. "It was remarkable to me how absent in their responses were any discussion of risk," Kass said.
On the other hand, many volunteers saw the trials as a financial opportunity, and most reported positive experiences. Nearly half said the money was the best thing about volunteering.
"They pay you well -- they seem to take an interest in making sure you understand what's going on," said one respondent.
The survey results also highlighted the satisfaction that many volunteers get from contributing to society. A third of them said "helping others" was the best part of volunteering.
Many volunteers work at the institutions where the research takes place and were nearly five times more likely than those recruited from outside the institution to list altruism as their major motivator.
Lynn Lewis, a 31-year-old research coordinator at the University of Maryland School of Medicine, said she joined her first study in 2001. Since then, she has signed on for a half-dozen.
"One of the first ones was for smallpox," said Lewis, who did not take part in the Hopkins survey. " I saw a poster on campus and I knew they needed volunteers for that after 9/11."
Lewis said she doesn't feel that the trials are risky but said that her husband disagrees. "We made a deal," she said, "that I wouldn't participate in tests of anything that isn't already FDA-approved."
She made an exception for her current trial, a year-long study of a potential measles vaccine for infants in developing countries at UM's Center for Vaccine Development.
"You can't test Phase 1 in children," she said. "It makes me feel really good knowing that what I've done will help people down the road."
Most clinical trails are regulated by the FDA or the Office for Human Research Protections of the U.S. Department of Health and Human Services.
Until the late 1970s, Phase 1 drug trials routinely enrolled healthy inmates in state and federal prisons, but federal regulators prohibited that practice in 1978. Now the trials are typically conducted at universities, government facilities, hospitals and private testing centers.
Every study must be approved by the organization's institutional review board (IRB), a committee established to ensure the trial meets government and institutional safety guidelines.
"We spend an awful lot of time trying to protect the human subjects," said Dr. Joseph A. Carrese, vice-chair of an IRB at the Johns Hopkins School of Medicine.
One major concern, he said, is ensuring that patients understand what they're signing up for. He said documents explaining the research are written at a middle school reading level, and researchers are trained to gauge whether potential volunteers understand the risks involved.
It's a struggle, he said, to balance the risk to volunteers with the need to advance medicine.
"We all have family members and neighbors who have illnesses," he said. "But we want to do [the medical research] the right way."
Kevin Lindamood, the vice president for external affairs at Health Care for the Homeless, agreed that the issue is complicated. His organization runs health clinics for homeless people in Baltimore but has refused to post fliers advertising Phase 1 trials. "By targeting very low-income people, it makes it a social justice issue," he said. "If someone is desperately poor, are they really able to give informed consent?"
He acknowledged, however, that the research offers perks to people who have few options. "It gets them a little bit of an income and gets them off the streets," he said.
Tom L. Beauchamp, a bioethics professor at Georgetown University, said that the only alternative for some disadvantaged people might be working as a day laborer, which has its own risks.
"It's all well and good to have a just society," he said. "But the fact is we don't have a just society."
Adil E. Shamoo, a professor at the University of Maryland School of Medicine, said Phase 1 trials are the most ethically challenging, because the participants are healthy and derive no medical benefit.
He argues that more research is needed to investigate the long-term effects that clinical trials have on volunteers' health and the number of adverse events they experience.
He also proposes a national registry of volunteers to ensure that volunteers wait 30 days between studies and don't join more than one at a time. Switzerland has recently implemented such a system.
While Shamoo thinks more could be done to reduce the risk of Phase 1 trials, he does not advocate removing money from the equation.
"This is a capitalist country, and people take risks for financial rewards," he said. "And no progress would be made without Phase 1."
chris.emery@baltsun.com