by Sonia Shah
But not everyone evaluates outcomes in the same way, which is, of course, the underlying logic of respecting others’ right to choose in the first place. “It is kind of a colonial or imperial attitude, if you like,” says prominent South African bioethicist Solomon Benatar. “There seems to be this idea that if you want to do a trial in Africa, and you want to set the same standards for that trial as you did in Europe or America, all you need to do is have the best proven drug. But the standard of care in a research study goes beyond the drug. . . . Until such time as you are paying the same amount of attention to the standard of informed consent, then I wonder why are you making so much noise about the drug? Is our mind-set framed by the pharmaceutical industry? Is our mind-set not framed enough by the conditions under which people live—and what it means to be treated with respect by a foreigner?”46
The FDA reviewed Pfizer’s data from Nigeria in early 1997. They didn’t question the statement indicating ethics committee approval. The fact that it had been backdated and the hospital in question didn’t have an ethics committee at the time of the trial didn’t emerge until 2001, after the Washington Post exposed the trial.47 Nor did the agency have anything to say about the utter lack of evidence of participants’ informed consent.48 On the contrary, when regulators indicated to Pfizer that the Nigerian trial wouldn’t fly, it wasn’t because of these ethical violations: rather, there were “discrepancies” in the data. Despite it all, the agency went on to approve Trovan for fourteen adult uses, the largest number ever for a drug’s initial approval.49
The complicity of regulators, industry researchers, and academic scientists in circumventing the requirement for informed consent is not limited to experiments conducted on unwitting, uncomprehending foreigners. Even in the United States, regulators have long turned a blind eye to coercion and misunderstanding between subjects and researchers.
The first clause of the Nuremberg Code, that experimental subjects be “able to exercise free power of choice,” indicated to most countries around the world the impermissibility of experimentation upon those forcibly restrained behind bars. And yet, when the 1962 amendments to the U.S. Food and Drug Act required that drug companies suddenly experiment on scores of living bodies, the U.S. prison population served as “almost the exclusive subjects” for early drug trials, according to a 1994 federal advisory committee report on government-sponsored human experimentation. Some pharmaceutical companies even built their testing laboratories next door to prisons to ease their access to the incarcerated masses.50
The practice of experimenting on prisoners only ended in the 1970s, when the Tuskegee study exploded onto headlines. In its wake, public mistrust in all human experimentation ran so deep that an influential 1974 Scientific American paper went so far as to argue that all placebo-controlled trials were profoundly deceptive, since some patients would think they were getting active treatments when in fact they weren’t. “To permit a widespread practice of deception . . . is to set the stage for abuse and growing mistrust,” the paper argued.51 Drug companies, sensing the change in the wind, quietly disassembled their prisoner drug-testing facilities. “We were getting too much hassle and heat from the press. It just didn’t seem worth it,” remembers an administrator from one of Eli Lilly’s test clinics at an Indiana prison.52
Despite the 1979 Belmont Report’s clear statement that human subjects must not be tempted into risky experiments by cash or other benefits,53 drug companies quickly found that offering a modest sum to broke students and homeless people provided a plentiful supply of recruits. Soon the industry’s test clinics had quietly migrated to the nation’s university campuses. Today Pfizer’s new test clinic conveniently nestles next to Yale University; Bristol-Meyers Squibb’s next to Princeton University; Glaxo’s next to Imperial College in London.54
Students and homeless people flock to the industry’s gleaming facilities. For Ben Leff, a University of Chicago law student, becoming a guinea pig netted him “more money than I had ever made doing anything,” he said. At a pay rate of around $100 to $200 a day, including room and board, “it’s money for doing almost nothing,” he exclaimed.55
Nineteen-year-old Traci Johnson took up experimentation to earn the $3,600 she needed to pay for a semester’s worth of tuition and fees at Indiana Bible College in Indianapolis. The bible college recommended students apply for jobs at the local post office or Starbucks, for example,56 but there was a better option just seven miles away from her school: volunteering as a research subject for experimental drug trials run by Eli Lilly. At $150 a day the job paid twice as much as the starting wage at Starbucks, and included board and a “hotel-like” room, not to mention a pool table, cafeteria, and rooftop sundeck.57 Other volunteers said the experience was less like a job and more like a “mini-vacation.” “It’s like staying in a really nice hotel,” one said. “The lobby view is gorgeous,” added another.58 Johnson could earn enough for another semester of school in less than a month.
In January 2004, Johnson checked into the Lilly clinic and enrolled in a study of duloxetine, an antidepressant in the same class—selective serotonin reuptake inhibitors (SSRI)—as Prozac. Over the following weeks clinicians gave her increasingly larger doses of the drug, up to six times greater than the recommended therapeutic dose, and tracked how she metabolized it.59 When not involved in study activities, Johnson and the other drugged subjects watched television and shot pool.
Meanwhile, across the Atlantic, British medical authorities were banning the use of SSRI drugs in people under the age of eighteen. Six months before Johnson’s enrollment in the trial, the FDA, sufficiently aroused, had ordered one of its researchers to investigate the growing body of evidence linking the drugs to suicidal behavior. As Johnson started the trial, the researcher had revealed his findings to his superiors in the agency: people under eighteen years of age who took the drugs were twice as likely to engage in suicide-related behavior compared to those who didn’t take them. The danger was greatest within four days of stopping the drug, he reported. The FDA decided to keep its findings secret.60
On or around February 3, the nineteen-year-old Johnson was taken off the duloxetine; the protocol called for placebos during the final four days of the study. Some subjects reportedly felt “uncomfortable” after being withdrawn from the drug, a Lilly doc noted, but not Johnson, apparently.61 On February 6, she called her best friend on the phone, laughing and sounding happy, as her friend remembers it.62 Johnson had, by then, earned $3,600 in the Lilly trial, enough to go back to bible school in the fall.
The next day she tied a scarf around the shower rod in her bathroom and hung herself.63
Two months after the FDA cleared the drug of any role in Johnson’s death and approved it for marketing, it ordered makers of antidepressants, including Lilly’s Cymbalta, to warn doctors that the drugs could increase the risk of suicidal thoughts and behavior in children and adolescents. By July 2005, the FDA had found a link between duloxetine and heightened rates of suicide attempts in adults as well: women taking the drug for relief from urinary incontinence.64
Some people have found they can eke out a meager living selling their bodies to industry science, flitting from center to center, enrolling in trial after trial for years at a time. Most such “professional volunteers” are students seeking to supplement their income, homeless people, or casually employed workers. “One guy in his forties had twenty-two kids and his girlfriend was pregnant,” Leff recalls about a fellow trial participant. “He did it for the diaper money.”65
For the research establishment, questions as to whether $200 a day is too much to offer to students and homeless people in exchange for their bodies, or whether such payments exploit the financial desperation of the poorest members of society, remain hazy and undecided. As the volume of Phase 1 trials expands virtually unhindered, such “ethical questions,” intoned the National Institutes of Health’s Neal Dickert and Christine Grady in a 1999 New England Journal of Medicine paper, “remain unresolved.
”66
Neither the country’s ethics committees nor the FDA have much to say on the matter: “oversight of the recruitment of subjects is minimal,” according to a withering 2000 Department of Health and Human Services report on the topic, “and largely unresponsive to emerging concerns.”67 Rather than acknowledge that they are buying access to human bodies for their trials, researchers tend to speak euphemistically. The “reimbursements” are small, they say: “We don’t pay patients to do clinical trials,” scoffed a clinical investigator at a Boehringer-Ingelheim research facility. “They get a fee for taking time out of their day and they get a fee for transport.”68
And yet it is clear from such publications as Guinea Pig Zero, which calls itself “the journal for human research subjects,” what brings eager volunteers to test clinic doors. “The pay rate is high-end and the studies tend to be long and lucrative,” a Guinea Pig Zero review of one research center noted. “They pay you for the travel and there are no unnecessary visits or procedures.” Little is mentioned about the mission of medical research, although the free laundromat, TV, and outdoor courtyard for dining all merit special attention.69 But even the most outspoken subjects don’t bother shattering the mythology that eases the investigator-subject relationship. As a researcher extracted her bone marrow, one subject recalls in a Guinea Pig Zero essay, “I just smiled and said I was glad to do my part for humanity.”70
For Phase 2 and Phase 3 trials, healthy subjects are not sufficient and recruitment becomes a bigger challenge. For these trials, sick people—patients—with the particular condition under consideration must be convinced to try out a new drug. With rich rewards in extended patent exclusivity on offer for companies that test their new drugs on children, sick kids and their parents must be enticed as well.
As the competition for access to these sick bodies has increased, subtly deceptive practices have become the norm. The problem lies in the fact that sick people are especially dependent upon the advice and authority of their clinicians. They are ill, and they need help. Generally, that isn’t a problem, as doctors are likewise enjoined by the Hippocratic oath to align their interests with those of their patients. But that isn’t the case in clinical trials. Here the doctor-investigator’s first commitment is no longer to the patient: it is to the data, whether the experiment helps the patient or not.
Of course, it is possible to fully inform patients about the differences between therapy and experimentation, and to acquire their voluntary consent. In earlier decades, when drug companies recruited sick patients for experiments by contracting with university hospitals, such distinctions were less problematic. Patients visiting research and teaching facilities had already implicitly signed on for cutting-edge, sometimes experimental methods.
But things started to change when the industry quit academia in favor of quick trials run by for-profit clinical trials companies such as CROs. CROs don’t fuss with pointy-headed university types. They approach doctors out in the community. The trouble is, when a patient visits her local doctor at the clinic on Main Street, she is expecting proven therapy, not experimental research, and the difference isn’t trivial, for doctors or patients. And as the pressures on community physicians to enroll ever greater volumes of patients at ever greater speeds grows, the incentive to blur the lines between therapy and experimentation intensifies.71
As HMOs pressure doctors to cut corners and spend less money and time on their patients, CROs offer doctors as much as $12,000 for simply enrolling a single patient into a trial,72 and they provide high-tech equipment. The work, after all, involves helping companies produce new drugs that help people. Today private practices, medical centers, and clinics actively compete for CRO contracts, scrambling for “a larger piece of the pie,” as University of California professor of medicine Thomas Bodenheimer wrote in a 2000 New England Journal of Medicine paper.73
In a reversal of earlier marketing efforts that advertised a clinic’s medical services for patients, clinics now advertise their patients for industry experimentation. “Looking for trials!” ran one typical ad cited in the 2000 Department of Health and Human Services report. “We are a large family practice with 5 physicians and 3 physician’s assistants . . . and a computerized patient data base of 40,000 patients. . . . We can actively recruit patients for any study that can be conducted in the Family Practice setting.”74
Some CROs even offer generous bonuses for those who can lure patients into trials fastest or in the greatest volume, dangling perks such as an author byline on a prestigious journal article. According to a clinician quoted in the Department of Health and Human Services report, if a bonus was available for a physician after enrolling, say, thirty subjects and the doc had twenty-nine already, “you could bet that the site would get the 30th subject.”75 Even the eminent former surgeon general, C. Everett Koop, got in on the action, negotiating a deal with Quintiles to funnel patients visiting his popular health-related Web site to the company’s clinical trial sites.76
By 2003, CROs were raking in nearly $70 billion a year finding human bodies for experiments,77 some of them growing even larger than their drug company clients.78 New companies have emerged as subcontractors to the exploding CRO industry. “Our specialty is delivering qualified, motivated patients to health care professionals who use your product, and to your clinical trial sites,” the patient recruitment firm ThreeWire advertises.79 “Your subjects are out there somewhere,” Clinical Solutions, another recruitment firm, writes on its Web site. “We can find them.”80
Do doctors thus enticed into providing test subjects bypass the strictures of informed consent? It’s not unheard of. In 1997, two physicians from a medical college in Georgia were indicted for faking the medical records of their schizophrenic patients in order to enroll them in lucrative drug trials.81 In the late 1990s, a University of Oklahoma–sponsored physician misled melanoma patients enrolled in a vaccine trial that it was the “best vaccine out there,” and failed to inform them of adverse effects, sparking a congressional inquiry.82
In 1996, a surgeon at the University of South Florida tricked sixty subjects into a study of an experimental cutting tool.83 In 1999, eighteen-year-old Jesse Gelsinger died in a Phase 1 study of a gene-transfer technique at the University of Pennsylvania; neither Gelsinger nor his parents had been informed of previously documented adverse events or the salient fact that the investigators who presided over Gelsinger’s care in the experiment had financial interests in the company that was commercializing the technique. In 2001, a healthy volunteer, Ellen Roche, died from the inhalation of a chemical irritant; she hadn’t been informed that the compound had already been proven dangerous to humans in previous studies. (In this case, the investigator hadn’t known either.)84
According to government investigators, most patients are by and large unaware that their blood draws, urine samples, and hospital visits are being pored over quite so intently by people other than their own doctor. When the letters and phone calls roll in, asking them if they’d be interested in participating in a clinical trial for their diabetes or arthritis, it probably seems like fortuitous serendipity. Later the patient is approached by his familiar physician, holding court in his familiar white coat in his familiar examining room. But this time the doc is conducting an experiment rather than providing care.
Surveys showed that the overwhelming majority of patients—nearly 90 percent, according to some studies—consent to experimental trials under the mistaken impression that they will personally benefit from them. Despite dutifully signing their informed consent forms, two-thirds have no idea what the purpose of the trial they joined is, researchers have found.85 “The idea that altruism is an important consideration for most patients with cancer,” wrote one lymphoma sufferer, a former industry researcher, “is a figment of the ethicist’s and statistician’s imagination.”86 Instead, the American Journal of Bioethics affirmed in 2003 that the therapeutic misconception—patients’ mistaken belief that experimental techniques will help t
hem—“is not the exception, but the rule in modern research.”87 “I guess everybody looks at it as grandeur, you know,” explained a subject of a placebo-controlled trial to Harvard Medical School researchers. “Saying, ‘wow, I’ll take this pill and everything will stop.’” “I was positive it [the trial] would help me,” another trial subject said. “I was positive going in and I was positive through the whole thing.”88
Recruitment firms and drug companies—even medical facilities—encourage the confusion. They describe the human participants they need not as subjects of an experiment but simply as patients. One cancer center wrote on its Web site that “a clinical trial is just one of many treatment options” available—as if a clinical trial were, indeed, the same as medical therapy.89 Physician investigators don’t generally inform their subjects of the generous recruitment fees and stock options they acquire after patients sign on the dotted line.90 Nor are subjects generally told that the biggest trials requiring the most patients typically stand the least chance of helping them. (The larger the trial, the lower the manufacturer’s expectation in the beneficial effect of the new drug.91)
“My oncologist is really encouraging me to sign up for the Herceptin trial,” a breast cancer patient wrote on a support group Web site in 2003, referring to new trials of the blockbuster breast cancer drug. “He’s actually trying to ‘scare’ me into it by going on and on about my ‘great risk.’ I am terrified now that if I don’t do it, I am basically choosing to die from this.”92 The physician’s subtle coercion (“enroll or you’ll die”) and misinformation (“I know this drug will help you”) worked: the woman ended up enrolling in the trial, desperately hoping that she didn’t get randomized into the placebo group.
