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Timothy Caulfield

Timothy Caulfield

Timothy Caulfield is a Chair in Health Law and Policy and a Professor in the Faculty of Law and the School of Public Health at the University of Alberta. He has won numerous academic awards, has appeared in publications such as Time, Newsweek, Wired, National Geographic, and Scientific American, and been involved with a number of national and international policy and research ethics committees. He is the author of The Cure for Everything: Untangling Twisted Messages about Health, Fitness and Happiness.
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White Coat, Black Hat:Adventures on the Dark Side of Medicine

Chapter One The Guinea Pigs

On September 11, 2001, James Rockwell was camped out in a clinical-research unit on the eleventh floor of a Philadelphia hospital where he had enrolled as a subject in a high-paying drug study. As a rule, studies that involve invasive medical procedures are more lucrative--the more uncomfortable, the better the pay--and in this study, subjects had a fiber-optic tube inserted in their mouths and down their esophaguses so that researchers could examine their gastrointestinal tracts.

Rockwell had enrolled in many previous studies at corporate sites, places like Wyeth and GlaxoSmithKline. But the atmosphere there felt professional, bureaucratic, and cold. This unit was in a university hospital, not a corporate lab, and the staff had a casual attitude toward regulations and procedures. “The Animal House of research units” is what Rockwell calls it. “I’m standing in the hallway juggling,” he says. “I’m up at five in the morning watching movies.” Although study guidelines called for stringent dietary restrictions, the subjects got so hungry that one of them picked the lock on the food closet. “We got giant boxes of cookies and ran into the lounge and put them in the couch,” Rockwell says. “This one guy was putting them in the ceiling tiles.” Rockwell has little confidence in the data that the study produced. “The most integral part of the study was the diet restriction,” he says, “and we were just gorging ourselves at two a.m. on Cheez Doodles.”

On the morning of September 11, nearly a month into the five-week study, the subjects gathered around a television and watched the news of the terrorist attacks through a drug-induced haze. “We were all high on Versed after getting endoscopies,” Rockwell says. He and the other subjects began to wonder if they should go home. But a mass departure would have ruined the study. “The doctors were like No, no!’ “ Rockwell recalls. “No one’s going home, everything’s fine!’ “ Rockwell stayed until the end of the study and was paid seventy-five hundred dollars. He used the money to make a down payment on a house.

Rockwell is a wiry thirty-year-old massage-therapy student with a pierced nose; he seems to bounce in his seat as he speaks, radiating enthusiasm. Over the years, he has enrolled in more than twenty studies for money, he estimates. The Philadelphia area offers plenty of opportunities for aspiring human subjects. It is home to four medical schools and is part of a drug-industry corridor that stretches from there into New Jersey. Bristol-Myers Squibb regularly sends a van to pick up volunteers at the Trenton train station.

Today, fees as high as the one that Rockwell received in 2001 aren’t unusual. The best-paying studies are longer, inpatient trials, where subjects are often required to check into a research facility for days or even weeks at a time so that their diets can be controlled, their blood and urine tested regularly, and their medical status carefully monitored. Occasionally, they also undergo invasive procedures, like bronchoscopies or biopsies, or suffer through something else unpleasant, such as being deprived of sleep, wearing a rectal probe, or having allergens sprayed in their faces. Because such studies require a fair amount of time in a research unit, the usual subjects are people who need money and have a lot of time to spare: the unemployed, college students, contract workers, ex-cons, or young people living on the margins who have decided that testing drugs is better than punching a clock with the wage slaves. In some cities, like Philadelphia and Austin, the drug-testing economy has produced a community of semiprofessional research subjects who enroll in one study after another. Some of them do nothing else. For them, guinea-pigging, as they call it, has become a job. Many of them say that they know people who have been traveling around the country doing studies for fifteen years or longer. “It’s crazy and it’s sad,” one drug-trial veteran told me. “For me, this is not a life. But it is a life for a lot of these people.”

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Most drug studies used to take place in medical schools and teaching hospitals. Pharmaceutical companies developed the drugs, but they contracted with academic physicians to carry out the clinical testing. According to the New England Journal of Medicine, as recently as 1991, 80 percent of industry-sponsored trials were conducted in academic health centers. Academic health centers had a lot to offer pharmaceutical companies: researchers who could design the trials, publications in reputable journals that could help market the products, and a pool of potential subjects on whom the drugs could be tested. But in the past decade or so, the pharmaceutical industry has been testing more drugs, the trials have grown more complex, and the financial pressure to bring drugs to market swiftly has intensified. Impatient with the slow pace of academic bureaucracies, pharmaceutical companies have moved trials to the private sector, which is where more than 70 percent of them were conducted in 2004.

This has spurred the growth of businesses that specialize in various parts of the commercial-research enterprise. The largest of the new businesses are called contract research organizations (CROs) and include Quintiles, Covance, Parexel, and PPD (Pharmaceutical Product Development), a company that has operations in thirty countries, including India, Israel, and South Africa. These firms are hired to shepherd a product through every aspect of its development, from subject recruitment and testing through FDA approval. Speed is critical: a patent lasts twenty years, and a drug company’s aim is to get the drug on the shelves as early in the life of the patent as possible. In 2000, when the Office of Inspector General of the Department of Health and Human Services asked one researcher what sponsors were looking for, he replied, “Number one--rapid enrollment. Number two--rapid enrollment. Number three--rapid enrollment.”

The result has been a broadening of the range of subjects who are used and an increase in the rates of pay they receive.

Most professional guinea pigs are involved in Phase I clinical trials, in which the safety of a potential drug is tested, typically by giving it to healthy subjects and studying any side effects that it produces. (Phase II trials aim to determine dosing requirements and demonstrate therapeutic efficacy; Phase III trials are on a larger scale and usually compare a new drug’s results with those of standard treatments.) The better trial sites offer such amenities as video games, pool tables, and wireless Internet access. If all goes well, a guinea pig can get paid to spend a week watching The Lord of the Rings and playing Halo with his friends in exchange for wearing a hep-lock catheter in one arm and eating institutional food. Nathaniel Miller, a Philadelphia drug-trial veteran who started doing studies in order to fund his political activism, was once paid fifteen hundred dollars in exchange for three days and two endoscopies at Temple University, where he was given a private room with a television. “It was like a hotel,” he says, “except that twice they came in and stuck a tube down my nose.”

The shift to the market has created a new dynamic. The relationship between testers and test subjects has become, more nakedly than ever, a business transaction. Guinea pigs are the first to admit this. “Nobody’s doing this out of the goodness of their heart,” Miller says. Unlike subjects in later-stage clinical trials, who are usually sick and might enroll in a study to gain access to a new drug, people in healthy-volunteer studies cannot expect any therapeutic benefit to balance the risks they take. As guinea pigs see it, their reason for taking the drugs is no different from that of the clinical investigators who administer them and who are compensated handsomely for their efforts. This raises an ethical question: what happens when both parties involved in a drug trial see the enterprise primarily as a way of making money

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In May of 2006, Miami-Dade County ordered the demolition of a former Holiday Inn, citing various fire and safety violations. It had been the largest drug-testing site in North America, with six hundred and seventyfive beds. The operation had closed down earlier that year, shortly after the financial magazine Bloomberg Markets reported that the building’s owner, SFBC International, was paying undocumented immigrants to participate in drug trials under ethically dubious conditions.3 The medical director of the clinic had gotten her degree from a school in the Caribbean and was not licensed to practice. Some of the studies had been approved by a commercial ethical review board owned by the wife of an SFBC vice president. (The company, which has since changed its name to PharmaNet Development Group, says that it required subjects to provide proof of their legal status, and that the practice of medicine wasn’t part of the medical director’s duties. In August 2007 the company paid $28.5 million to settle a class-action lawsuit.4)

“It was a human-subjects bazaar,” says Kenneth Goodman, a bioethicist at the University of Miami who visited the site. The motel was in a downtrodden neighborhood; according to later reports, paint was peeling from the walls, and there were seven or eight subjects in a room. Goodman says that the waiting area was filled with potential subjects, mainly African American and Hispanic; administrative staff members worked behind a window, like gas-station attendants, passing documents through a hole in the glass.

The SFBC scandal was not the first of its kind. In 1996, the Wall Street Journal reported that at its testing site in Indianapolis, Eli Lilly and Company was using homeless alcoholics from a local shelter to test experimental drugs at budget rates. (Lilly’s executive director of clinical pharmacology told the Journal that the homeless people were driven by “altruism” and that they enrolled in trials because they “want to help society.” The company says that it now requires subjects to provide proof of residence.) The Lilly clinic, the Journal reported, had developed such a reputation for admitting the down-and-out that subjects traveled to Indianapolis from all over the country to participate in studies.5

How did the largest clinical-trial unit on the continent recruit undocumented immigrants to a dilapidated motel for ten years without anyone’s noticing? Part of the answer has to do with our system of oversight. Before the 1970s, medical research was poorly regulated; many Phase I subjects were prisoners. Reforms were instituted after congressional investigations into abuses like the four-decade-long Tuskegee syphilis studies, in which researchers observed, instead of treating, syphilis infections in African American men. For the past three decades, institutional review boards, or IRBs, have been the primary mechanism for protecting subjects in drug trials. FDA regulations require that any study in support of a new drug be approved by an IRB. Until recently, IRBs were based in universities and teaching hospitals and were made up primarily of faculty members who volunteered to review the research studies being conducted in their own institutions. Now that most drug studies take place outside academic settings, research sponsors can submit their proposed studies to for-profit IRBs, which will review the ethics of a study in exchange for a fee. These boards are subject to the same financial pressures faced by virtually everyone in the business. They compete for clients by promising a fast review. And if one for-profit IRB concludes that a study is unethical, the sponsor can simply take it to another.6

Moreover, because IRBs scrutinize studies on paper only, they are seldom in a position to comment on conditions at a study site. Most of the standards that SFBC violated in Miami, for example, would not be evaluated in an ordinary off-site ethics review. IRBs ask questions like “Have the subjects been adequately informed of what the study involves” They do not generally ask if the sponsors are recruiting undocumented immigrants or if the study site poses a fire hazard. At some trial sites, guinea pigs are housed under conditions that would drive away anyone with better options. Guinea pigs told me about sites that skimp on meals and hot water or that require subjects to bring their own towels and blankets. A few sites have a reputation for recruiting subjects who are threatening or dangerous but who work cheap.

Few people realize how little oversight the federal government provides for the protection of subjects in privately sponsored studies. The Office for Human Research Protections, in the Department of Health and Human Services, has jurisdiction only over research funded by the department. The FDA oversees drug safety, but, according to a 2007 HHS report, it conducts “more inspections that verify clinical trial data than inspections that focus on human-subject protections.” In 2005, FDA inspectors were finally given a code number for reporting “failure to protect the rights, safety, and welfare of subjects,” and an agency spokesman says that they planned to make more human-subject-safety inspections in the future, but as of early 2008 they had cited only one investigator for a violation. (A psychiatrist had held a research subject in his Oklahoma research facility against her will for four days after she tried to drop out of a drug trial. The psychiatrist had also been disciplined by the state licensing board for giving herpes to two of his patients.) In any case, the FDA inspects only about 1 percent of clinical trials.

The guinea-pig pro has a delicate relationship with trial recruiters. Technically speaking, recruiters are supposed to frown on the practice of serial guinea-pigging. It is not clear what sort of data is generated by trials on people who have recently been taking many other drugs. Nor is it clear what toll these experimental drugs are taking on the long-term health of the guinea pigs themselves. For these reasons, most sites require that guinea pigs wait at least a month after one trial has ended before enrolling in another one. In practice, however, that requirement is sometimes handled with a wink and a nod. If a guinea pig behaves in a study, he may find himself recruited for a new one before he even leaves the trial site.

Yet because their motivation for doing studies is purely financial, guinea pigs have a concrete incentive to lie about their medical history in order to qualify. “If you don’t lie then you’re talking yourself out of a job,” one guinea pig told me. Guinea pigs learn never to admit that they have been sick, that they have used illicit drugs, or that they have recently been in another study. However, once guinea pigs are accepted into a study, they are given financial incentives to stay in. Many sponsors penalize guinea pigs for missing follow-up appointments, and some back-load the pay scale so that guinea pigs have to stay in a study until the end in order to get most of their money. The only way for a subject to get out of a study without being penalized is to experience side effects so severe that the sponsors decide the guinea pig must be dropped.

James Rockwell told me of a time when he enrolled in a thirty-day outpatient study of a drug for Alzheimer’s disease that required him to get dosed every morning before he went to work; he painted houses, which involved standing on high ladders. At one point during the study Rockwell decided to leave town to participate in a political demonstration. But this would have meant forfeiting part of his pay. “I decided to fake a story about fainting on the job,” he says, which meant he’d be dropped from the study but would still get paid. The Merck doctors tried to persuade him to drop out of the study voluntarily, but Rockwell stood his ground. When he was eventually dropped, it was with full compensation.

Most guinea pigs rely on their wits--or on word of mouth from other subjects--to determine which studies are safe. Some avoid particular kinds of studies, such as trials for heart drugs or psychiatric drugs. Others have developed relationships with certain recruiters whom they trust to tell them which studies to avoid. In general, guinea pigs figure that sponsors have a financial incentive to keep them healthy. “The companies don’t give two shits about me or my personal well-being,” Nathaniel Miller says. “But it’s not in their interest for anything to go wrong.” That’s true, but companies also have an interest in things going well as cheaply as possible, and this can lead to hazardous trade-offs.

The most notorious recent disaster for healthy volunteers took place in March 2006 at a testing site run by Parexel at Northwick Park Hospital, outside London; subjects were offered two thousand pounds to enroll in a Phase I trial of a monoclonal antibody, a prospective treatment for rheumatoid arthritis and multiple sclerosis. Six of the volunteers had to be rushed to a nearby intensive care unit after suffering life-threatening reactions--severe inflammation, organ failure. They were hospitalized for weeks, and one subject’s fingers and toes were amputated. All the subjects have reportedly been left with long-term disabilities.

The Northwick Park episode was not an isolated incident. Traci Johnson, a previously healthy nineteen-year-old student, committed suicide in a safety study of Eli Lilly’s antidepressant Cymbalta in January of 2004. (Lilly denies that its product was to blame.) I spoke to an Iraqi living in Canada who began doing trials when he immigrated. He was living in a hostel and needed money to buy a car. A friend told him, “This thing is like fast cash.” When he enrolled in an immunosuppressant trial at a Montreal-based subsidiary of SFBC, he found himself in a bed next to a subject who was coughing up blood. Despite his complaints, he was not moved to a different bed for nine days. He and eight other subjects later tested positive for tuberculosis.
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