Contrary to public assurances that clinical trials are highly regulated and safe enough for children. Congress enacted a law in 1997 (FDAMA-FDA Modernization Act) encouraging the use of children as drug testing subjects by giving drug manufacturers a six month patent extension for drugs tested in children. But the reality is, clinical trials are fraught with hazards for the human subjects involved.
Everyone other than the subjects who is involved in this enterprise has unacknowledged conflicts of interest: beginning with corporate sponsors who spend $14 billion each year to test experimental compounds in the hope of gaining marketing approval from the FDA; the doctors, the hospitals, the ethics committees (institutional review boards, IRBs) who are supposed to be the watchdogs; and those who are paid to recruit subjects, or to dispense the experimental substances—all have a financial stake. Even government agencies whose mandate is to protect the safety and welfare of subjects are tacit accomplices in helping industry keep vital information hidden. They get involved only after harm is done, after major violations have been reported, then couch their letters of determination in non-judgmental bureaucratic language. Thus, regulatory safeguards for human subjects are about as reliable as FEMA during a hurricane.
In Northwick Park hospital (UK), all six volunteers who had been exposed to TGN1412, an experimental compound (for leukemia) suffered acute organ failure. Bloomberg News had run a sensational investigative series in December, 2005, that uncovered a host of unethical corrupt practices by those conducting clinical trials, including failure to protect healthy volunteers from contagious diseases. In Montreal, 11 healthy volunteers contracted tuberculosis after being exposed to an infected volunteer at the hospital.
A shortage of willing volunteers has led to more aggressive recruitment practices by contract research organizations (CROs) hired by manufacturers. The Bloomberg series gave readers insight into the seedy side of this very lucrative business whose stakeholders are cutting ethical corners to speed up the process and thereby increase risks for subjects. Parexel, the U.S. company conducted the TGN1412 UK trial for a German drug manufacturer, while SFBC was responsible for the Montreal debacle. See links to Bloomberg series at: https://ahrp.org/infomail/05/11/03.php; https://ahrp.org/cms/content/view/117/29/
An editorial in the BMJ, by Michael Goodyear, assistant professor, Department of Medicine, Dalhousie University, raises important questions and highlights some of the heretofore ignored systemic pitfalls of medical research: “This allegedly unprecedented event in clinical research represents a very human tragedy, one which will probably change forever the face of clinical drug development and testing, and one which gives us the opportunity to learn many valuable lessons. A system based approach to learning is more likely to generate useful outcomes than one that is narrowly explanatory and blame oriented. Yet health care has been learning this lesson slowly and painfully. Nobody should be surprised that this disaster happened: even rare events have finite probabilities.”
“Had this trial been available for public review, potential problems might have been identified and avoided.”
The editorial prompted AHRP board member (Treasurer), John H. Noble, Jr. Professor Emeritus, SUNY/Buffalo, to add:
“Michael’s rhetorical question about why secrecy except to avoid
liability for bad things that may happen to human subjects is, IMHO, the central issue. The issue is amplified by the confounding of legal provisions to protect "trade secrets" by industry to maintain competitive advantage as well as to defend against negligent harm for which it may be responsible.”
Witness the article by Barry Meier in today’s New York Times about the results of an external inquiry about what went wrong in the marketing by Guidant of a potentially defective heart defibrillator. See: http://www.nytimes.com/2006/03/22/business/22guidant.html?ex=11436948
It contains an amazing quotable quote, ‘The light went on," he said, "and one of the things that we realized is that industry had to be transparent with physicians about these devices so that physicians could be transparent with patients.’”
“The ‘light went on’?! This is a ‘No s***, Dick Tracy’ proposition.”
“How could the obvious have been missed–except by those whose singular focus was the pursuit of profit and market share, devil take the hindmost? The economics of such corporate behavior creates externalities for all who must pay without benefit by failing to internalize the full cost of production. It pollutes the biomedical research enterprise and undercuts the efficient allocation of scarce resources.”
“Furthermore, secrecy corrupts science. It militates against the basic criterion of science, namely, the reproducibility of results. Current law and FDA practice vis-a-vis protecting "trade secrets" both undercuts scientific progress and provides cover for those who seek to avoid liability for the bad things that avoidably happen to human research subjects.”
“Bottom-line, transparency is needed to protect physicians and their patients against foreseeable harm as well as to protect the integrity of the scientific enterprise.”
Among the highly publicized previous human casualties of research are: Nicole Wan, 19 (University of Rochester); Jesse Gelsinger, 18 (University of Pennsylvania); Ellen Roche, 27 (Johns Hopkins); Elaine Holden-Able, a healthy retired nurse (Case Western); Tracy Johnson, 19 (Eli Lilly).
An article in Cleveland Scene Weekly (below) describes the highly sought after pool of potential human guinea pigs: medical school students who sign up for the cash—some netting $10,000 a year.
Contact: Vera Hassner Sharav
Cleveland Scene Weekly
Guinea Pig Gang
Meet the students who rent their bodies to science — and have the scars to prove it.
By Rebecca Meiser
Mar 22, 2006
On a Thursday morning in February, Nikolai Sopko rushes through the halls of University Hospitals. He’s a short, boyish 25-year-old with the body of a former varsity wrestler. He’s 15 minutes late for an appointment at the skin-studies center. "Fifth floor!" Sopko calls out as he enters the crowded elevator. When the doors open, Sopko dashes out, heading toward the skin-care office. He’s a few feet away when a hot-pink sheet of paper catches his eye:
Volunteers needed. Monetary compensation available.
Sopko’s blue eyes scan the page. "How come I haven’t heard about this one before?" he says aloud, sounding pissed. He quickly scribbles down the details. Five minutes later, he enters the skin-studies clinic. "Nikolai!" cries Heather Scull, a research coordinator with the flawless skin and cheerful demeanor of a Midwest pageant winner. "It’s been a while," she says, giving Sopko a hug. Sopko squeezes back politely, but is obviously displeased. "Heather," he says accusingly, "why do I not know about this psoriasis study?" "It’s a new one," Scull protests. "We just found out about it. Are you interested in volunteering?"
Of course he is. Sopko, a medical student at Case Western Reserve, is among the best-known human guinea pigs in town. Over the past five years, he’s made more than $7,000 letting doctors poke, prod, and even burn him. He has undergone electroshock and waited out 10 MRIs. Today, Sopko is directed to a leather reclining chair. He rolls up the sleeves of his Lacoste polo shirt to reveal a muscular forearm. Scull unwraps a short butterfly needle, attaches it to a plastic syringe, and slips it into his vein. Sopko never winces, preferring to chat about his upcoming spring-break trip to the Bahamas. At the end of the 15-minute procedure, Scull has harvested four syringes of blood. Sopko yawns, mumbles something about heading back to bed, and reminds Scull again to call him if she hears of any more studies. "We have lots of regulars: people we call on last-minute for studies," Scull says, shaking her head in bemusement. "But there are few people who are willing to do the type of experiments Nikolai does."
About 20 million people a year participate in clinical trials. Most have good reason to volunteer: It’s a matter of life and death. For people in the final stages of cancer, even a small chance of survival is worth the discomfort. But a smaller subgroup volunteers for scientific studies as a part-time job. They’re typically students leading a lifestyle beyond their means and unwilling to work a traditional job at a fast-food joint. They’re professional human guinea pigs, and their numbers are increasing.
"These are the type of people who think only of immediate gratification," says Vera Hassner Sharav, president of the Alliance for Human Research Protection. "They’re not thinking of the consequences or of the future."
Ask the guys in the guinea-pig trade, however, and they don’t feel like victims. Bob Helms is perhaps the best known among them. He’s the author of Guinea Pig Zero, a fanzine started in Pennsylvania in 1996 and anthologized in a book of the same title in 2002. "For us, it’s just a job," Helms says. "As with any other jobs, you’ve just gotta be aware of what you’re getting into."
Cleveland’s abundance of nationally renowned hospitals makes it particularly easy pickings for aspiring guinea pigs. Over the past four years, medical institutions in Cleveland have conducted hundreds of clinical studies, requiring thousands of volunteers. For hospitals, attracting participants can be the hardest part of conducting a study. Many people avoid the doctor, even when they’re sick; those who are willing to become human pincushions for below minimum wage are a rare breed. Just ask Nilofar Syed. Two years ago, the research assistant had to find healthy female volunteers to serve as the controls in a study about hair loss. She put ads in Cleveland Magazine, hung fliers at the Case Western Reserve campus, and e-mailed more than a hundred members of her med class. It still took three months to get 30 volunteers.
Among the many volunteer subjects in Cleveland, Sopko and two of his friends — Jason Snyder and Nick Pesa — take the profession more seriously than most. Call them the Guinea Pig Gang. They stalk medical-center bulletin boards, bookmark websites that list area trials, and swap info with other professional guinea pigs. "Departments are always looking for people to serve as healthy controls," says Snyder, a first-year podiatry student. "Just because you see a sign advertising a psoriasis survey doesn’t mean you have to have psoriasis."
Still, clinical studies aren’t without risk. Each year, hundreds of participants develop what are technically called "adverse reactions" — everything from headaches and nausea to, in rare instances, death. But Sopko and his friends don’t worry about such things. They’re young, healthy, and suffering from a shared condition: They believe they’re invulnerable. The group fell into the human guinea-pig trade by accident. One afternoon in the fall of 1999, Snyder, a Case freshman with gangly limbs and a mop of dark brown hair, was walking to calculus class when he spotted a flier stapled to the math department’s bulletin board:
Wanted: Volunteers needed for a skin study. Compensation given.
Snyder, who often found himself short a dollar, ripped off the phone number and stuffed it in his pocket. Later that day, he called the center to learn more. The clinic needed several dozen healthy, fair-skinned volunteers for a study involving UV rays, an assistant told him. The pay was $150. Snyder signed up.
When he walked into the clinic, he was greeted by two research assistants, who asked him to fill out a few pages of consent forms. Then they asked him to drop his drawers. The assistants used a natural-light simulator to give the equivalent of a sunburn to 10 small patches of Snyder’s right buttock. The next day, they rubbed cream on the marks. They wanted to see how the cream affected the burns. "It didn’t hurt at all," Snyder says. "I didn’t notice any pain whatsoever. And for an hour of my time, I made $150." Snyder bragged up his experience to Pesa and Sopko. They wanted in too.
Aspiring med students, they were all too aware of potential risks. So they resolved to be mindful of four rules as they plied the guinea-pig trade:
1) There should be minimal chance of permanent damage. "In Chicago, they were paying 10 or 15 thousand dollars to slice off your toe and then surgically reattach it," says Snyder.
2) The money had to be worth their time. "Some studies draw blood for, like, five dollars. That’s not acceptable," Snyder says.
3) They must know ahead of time what painkillers the clinicians plan to use. "Morphine, for example, is a nice anesthetic, because it goes through the entire body," Pesa explains.
4) The study should be sponsored by a reputable institution. This last rule allows for exceptions. Says Sopko: "If someone would pay me for some clinical study in their kitchen, I’d probably do it, if rules one to three were in place."
With the guidelines set, the friends signed up for every study they could find. Freshman year, they averaged $80 dollars per study and netted about a $2,000 profit. Before long, they were doing approximately half a dozen studies a month. By sophomore year, Pesa had stumbled onto an even more lucrative racket. The Beachwood branch of the Cleveland Clinic was starting a study about male infertility. In order to calibrate healthy sperm counts, clinicians needed 40 male donors. Volunteers would be asked to masturbate once a day, drive over to the Clinic, and place the sealed sample in a convenient drop-off box. The study paid $35 per sample. Pesa, a former honor student at Aurora High School, could do the math: Five samples a week for six months would earn him $4,600. All for doing something most men do for free. "I think I was one of the last ones to get in," he laughs. "It’s been closed off ever since." Last year, Pesa crested $10,000 in profits from the study. But the dough isn’t going toward spring-break cruises or season tickets to the Cavs. "My dad is making me put the money into savings," Pesa laments.
Often, the best money is in long-term studies that require follow-up interviews. They’re the gift that keeps on giving, the guinea-pig version of a stock that pays dividends. During his freshman year, Snyder volunteered for a long-term study to test a new drug for bipolar disorder. All Snyder had to do was drink a serotonin-laced chocolate milkshake. "It tasted horrible," Snyder recalls. "It had the consistency of sour milk." The $150 he earned more than made up for it, Snyder says, but the best part was that "every month afterwards for an entire year, I went in to talk to a psychologist. He’d ask me, ‘Are you depressed?’ I’d say, ‘No,’ and he’d hand me $50." All told, he earned $900.
In 2001, Elaine Holden-Able, a healthy 70-year-old nurse, volunteered for an Alzheimer’s study at University Hospitals. Clinical assistants gave her a concentrated dose of methionine, a dietary supplement. Later that day, Holden-Able felt weak and dizzy. Before long, her cardiac and respiratory systems collapsed. She fell into a coma. One month later, she was dead. Investigators later found 10 times the normal dose of methionine in Holden-Able’s blood. "We can’t prove that she got an overdose, but I can’t think of any other explanation," one of the researchers who reviewed the case said at the time.
Nonetheless, the Office for Human Research Protection, the federal office that regulates government-financed clinical studies, cleared University Hospitals of all wrongdoing. The office found "no evidence to substantiate" allegations that researchers failed to minimize the risks to participants. That’s no surprise to people familiar with human guinea-pig work. "Medical experiments are like an unknown adventure," says Sharav, the president of the patient-advocacy group. "It’s really like a wild, wild west culture, with unsuspecting subjects being exposed to greater risks than they ever bargained for. Some investigators’ attitude is shoot first, wait, and see what happens."
For a long time, human guinea pigs had even less protection. In the now-infamous Tuskegee experiments, black men with syphilis were denied access to the penicillin that would heal them. From the late 1950s to early 1970s, children at the Willowbrook State School for the Retarded in New York were intentionally infected with hepatitis to test a new cure. And in the early ’60s, doctors at the Jewish Chronic Disease Hospital in Brooklyn injected elderly patients with live cancer cells to study immune response. Public outcry spurred the discontinuation of such studies and the creation of the Office of Human Research Protection to oversee government-financed trials. The Food and Drug Administration was assigned to monitor privately funded studies.
Adverse reactions are supposed to be reported to either the FDA or the OHRP, but the scope of the injuries is rarely publicly disclosed. CenterWatch, a Boston-based research group that compiles data on clinical studies, says that on average, 17,200 adverse reactions occur each year, and 1 in 30 study participants experiences side effects serious enough to require hospitalization. Fortunately, deaths are much rarer, though not unheard-of. CenterWatch estimates that 1 person out of every 10,000 dies each year as a result of participation in clinical trials. "This is what the Office of Human Research Protection does: If there’s a dead body, they’ll come sniffing around. If there’s no dead body, they won’t even respond," says Helms, the fanzine publisher. "They don’t even keep records of injuries. The office is so inadequate, it’s just a total joke."
It’s a lesson that Pesa has already learned the hard way. Last fall, he agreed to undergo a clip biopsy of his lungs — an operation in which doctors snip a small piece of tissue from inside the patient’s lungs. Despite the unnerving sound of the procedure, Pesa remained unconcerned; he had learned in med school that the lungs have no pain receptors. "Theoretically, I shouldn’t have felt anything," he says. Besides, the study paid $300. Pesa headed to the department in the late afternoon. Per protocol, the research assistants informed Pesa about the procedure and risks. Pesa’s mind drifted to a gym workout he was planning for afterward. ". . . and one patient died while participating in this study," the clinical assistant said. Suddenly, Pesa snapped to attention.
The victim, the clinical assistant assured him, had already been suffering from extreme asthma. Since her death, they’d added more security measures and the procedure was now considered much safer. Pesa considered his options: Drop out and forgo the $300, or — "I’ll do it," said Pesa. An hour and a half later, the surgery was over. But recovery wasn’t the cakewalk it had been made out to be. Pesa felt as if he’d been stabbed in the lung. "I didn’t think it was going to hurt as much as it did," Pesa says. "For a good couple of days afterwards, it really sucked."
Sopko can relate. After college, he was awarded a fellowship as a kidney-cancer researcher at the National Institutes of Health in Bethesda, Maryland. It was a dream job in more ways than one. The NIH is considered guinea-pig heaven. "The prices they pay at NIH are, like, eight times higher," he says. Sopko signed up to take 10 MRIs — "They pay $120 each, and all I did was lay there and do calculus in my head," he explains — and an anxiety study.
With the anxiety trial, researchers wanted to see whether an experimental drug could reduce panic levels. To measure the drug’s performance, a clinical assistant would shock Sopko with electricity. But first, a clinical assistant inserted an IV in his arm. "It might not have been so bad, except the guy kept jabbing me with the needle in the wrong place," Sopko says, rubbing the inside of his elbow as he recounts the story. "It hurt like hell." The study earned him $850, but Sopko said he’d never repeat it. "I had bruises for a long time afterwards," he complains.
It wasn’t his only bad experience. For the study on the effects of UV light on skin, Sopko allowed doctors to singe a small section of his backside. Before Sopko signed the consent form, clinical assistants casually mentioned that discoloration of the skin might last for months and that "mild scarring" may be permanent. They weren’t kidding. Six months later, Sopko still had angry red marks that looked like rug burn. "On the plus side," Sopko says, "I got $150."
If the studies sometimes cause unexpected pain, they can also occasionally provide life-saving intervention. When Snyder volunteered for the bipolar study, it required him to undergo a thorough physical, which included testing by an EKG to measure his resting heart rate. In the hospital room, Snyder pulled off his shirt. Assistants placed sticky electrode pads on his chest and upper body. Almost immediately, the EKG machine started beeping loudly, signaling an abnormal heart rhythm. Assistants scrutinized the printout, but couldn’t find the source of the problem. "It’s probably nothing," one assistant assured Snyder, but a doctor ordered an ultrasound of his heart just to be sure. The ultrasound brought even more worrisome news: Snyder had a heart defect that pumped blood directly into his lungs, creating a potentially fatal strain on the circulatory system.
Scared, Snyder met with Dr. Roger Mee, a well-known pediatric heart surgeon at the Cleveland Clinic. Mee concluded that Snyder’s heart had been flawed since birth. No doctor had caught it, probably because the condition is so rare. Only three other cases have been recorded. "It’s so rare, it doesn’t even have a name," Snyder says. Snyder didn’t need to undergo immediate surgery, but every five years he will have to submit to a cardiac catheterization, a test that measures the heart’s pumping ability and the oxygenation of the blood. "It was nice to find this out," Snyder says. "In general, my parents are not thrilled about me doing these experiments, but in this case, they don’t really have much of an argument."
Over avocado rolls at Sushi on the Square, Sopko and Pesa relive their human guinea-pig stories, each trying to top the other. "You know, the lung biopsy really wasn’t that bad," Pesa says, dipping a roll into a dish of low-sodium soy sauce. "I’d probably do it again, no problem." Pesa’s girlfriend Rachel picks at a piece of sashimi and rolls her eyes. "You were in agony," she says. "They told you not to talk for, like, three days." It’s been a fun ride for the friends. They joke about the funny stories they’ll tell their grandchildren. But the end is in sight. Once they graduate and become doctors, they don’t plan to continue the guinea-pig lifestyle.
"Being lowly med students right now, our time’s only worth, like, $15 an hour," Pesa explains. "But when we’re surgeons and billing hundreds an hour, it won’t be worth it to keep participating." In an unexpected way, the friends say, their experiences as human guinea pigs furthered their education as physicians. "The average doctor isn’t going to understand how uncomfortable some of these tests can be," Sopko explains. "They’re not going to know how it feels to be treated like an object." Pesa nods. "And something like a skin biopsy — that gets ordered a lot," he adds. "If a patient seems worried about it, I can say, ‘You know, I’ve been through a biopsy. I’ve been through a lot worse procedures.’" Pesa grabs the last California roll with his chopsticks.
"Then," he says, "I can show them the scars."
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