The Body Hunters (24 page)

The best evidence of voluntary, informed consent is when some subjects drop out or refuse to participate in a trial, researchers say. “That's a good sign,” one noted to NBAC researchers. “They are able to refuse, they are free to refuse [to enroll].”
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And yet, in NBAC's 2001 survey of researchers active in developing countries, 45 percent reported that their low-literacy subjects
never
refused to participate.
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“I want the money,” explained Thai taxi driver Wivat Chotchatmala, a drug user who enrolled in one of VaxGen's HIV vaccine trials.
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“We continued to visit the distribution center” to participate in a U.S.-government sponsored trial of a new antimalarial drug, said Kenyan villager Lucas Oyombe Otieno, “so as to enjoy the free meals.” Otieno and his fellow subjects had already stopped taking the study drug because of its unpleasant side effects. “We would collect our drugs, pretend to swallow them, but we would throw them away later,” he told the
East African Standard
in 2004. “When they offered to provide us food, many of us accepted to be used in the study,” added Andrew Okal Seda, who enrolled in a similar antimalarial drug study in Kenya. “Around that time, there was widespread famine in the area.”
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And the truth is that, contrary to the blithe pronouncements of the NBAC and others that research can only proceed when subjects are informed and participate consensually, for some CROs, uninformed, coerced subjects don't impede medical research at all. On the contrary, unknowing, docile subjects make trials easier and faster.

“Russian subjects don't miss appointments, they take all the required pills, they fill in the questionnaires and the diaries, and only very rarely do they withdraw their consent. . . . Russian subjects do what their doctors tell them to do. What a phenomenon!” a promotional article in the trade journal
Applied Clinical Trials
gushed.
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CROs routinely tout the “compliance” of their experimental subjects on offer, especially those in poor countries where many patients are lucky if they can get a doctor to pay attention to them at all. James Loudon, an executive from a CRO active in China, encouraged drug companies to experiment on patients there, not because the patients are empowered and informed, but because “the Chinese are not that fully emancipated as in the U.S. They are more willing to be guinea pigs,” he said to CenterWatch in 2002. “It's not like Japan, where it's difficult to get patients to do trials, or they refuse at the last minute.”
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It isn't technically difficult to ensure that even the most
unknowing, premodern, and illiterate subjects are informed and consensual partners in high-tech medical research. Scientific notions ingrained in Western society may be foreign to others, but they are not beyond comprehension. “You can do it, if you put in enough resources,” says Anne-Valerie Kaninda, an aid doctor who treated meningitis-stricken children in the same Kano hospital where Pfizer conducted its Trovan test. “People are not as stupid as they are portrayed. I understand that it might be difficult to talk about informed consent when you are coming in with Western concepts of medicine, and there you have a mother with a sick child who doesn't know what a microbe is. But still, if you put in enough resources, with a translator you can still explain, ‘You have a choice, either you go the regular way, or you come with us; we are testing.' . . . It means that whoever is conducting the trial has to put resources into that, with a lot of well trained people.”
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Several simple methods have been shown to bridge the gulf between Western investigators and patients from developing countries. Researchers can take advantage of the fact that some patients in developing countries are more capable and inquisitive than their Western counterparts by virtue of having survived in more difficult, resource-constrained environments.
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After subjects sign the forms, researchers can quiz them. Those with low scores can be counseled further, or dropped from the trial. Study staff can hold periodic meetings with subjects to answer questions as they come up and ensure their participation remains voluntary.
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Researchers can hire local people to explain the study, by using pictures and diagrams, and references to local practices in agriculture or community life. They can launch educational programs about the experiments in the larger community. They can approach community leaders to help establish legitimacy first.
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If after all this, informed consent is still not achieved, then the prudent response might be similar to that taken when a piece of crucial equipment fails. The study, rendered untenable, is abandoned. Such practices might stymie some trials, but “not all knowledge is accessible,” says bioethicist Jonathan Moreno. “It is
one of the trade-offs between realizing there is a moral difference between people and lab rats.”
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But in many cases, that is not what happens.

Instead, researchers and regulators profess defeat—and press on anyway. They try and they try, but getting impoverished, illiterate villagers to understand and consent to their experiments is simply very difficult, if not impossible, some insist. M. Upvall and S. Hashwani of Aga Khan University in Pakistan compared informed consent procedures in Pakistan and Swaziland for a 2001
International Nursing Review
paper. According to their study, researchers were often forced to penetrate layer after layer of tribal hierarchy and corrupted bureaucracy in order to obtain informed consent. Sometimes they had to ask the village elders or the husbands of women participants first, or employ police escorts, or have tea and snacks, “regardless of the time it took.” Plus, they had to struggle with the fact that some subjects don't have telephones, or permanent addresses, and may even be afraid to sign their names. Such findings on the barriers to informed consent “demonstrate the inadequacy and complexity of applying western-based concepts of informed consent to developing countries,” Upvall and Hashwani wrote.
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It is a pointless exercise, some researchers insisted to NBAC analysts in an anonymous 2001 survey. In some African languages “there is no word for ‘research' or ‘science,'” one says. “There is no concept of an experiment or placebos.”
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“Informed consent is a joke,” said another. “It is not possible to claim a person who has never heard of a bacteria or virus is informed about what a vaccine or drug is doing or how their participation fits into any such study.”
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Perhaps informed consent is just too Western a notion, they say. After all, “this concept of the consent of the individual, rights, and individual decision-making doesn't exist” in many authoritarian developing countries, one said. “People do what they are told, and people are told what to do.”
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In India, according to a 1996
Journal of the Royal Society of Medicine
paper, physicians consider informed consent “an unnecessary ritual.”
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In Latin America, one doctor told the
Washington Post
in 2000,
physicians were “against” informed consent. “Patients want doctors who say, ‘Do this because I say so.'”
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Some industry researchers are even more forthright. They must mislead subjects because “if all potential adverse effects are listed in the informed consent, the patient will be scared away,” as John C.M. Lee, a Bristol-Myers Squibb researcher working in China wrote. “One needs some flexibility in implementing” requirements for informed consent. Due to educational and cultural background, a complete written informed consent is very difficult to achieve. It is a very long-term goal that China follow the international standard in this area.
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Even regulators profess impotence. “We have requirements for informed consent,” says the FDA's Robert Temple, but “I'm not going to tell you it is always well done. . . . Should there be more real-time interviews? Some ethicists talk about this. It is an area that needs attention. But we don't do anything about it immediately. We rarely go to a study that is ongoing.”
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Not a single subject signed a form indicating his or her consensual participation in Pfizer's Trovan experiment in Nigeria. The children were too young to sign, the company said in its defense, and the parents didn't speak English, the language the form was in. But in addition, no witnesses attested to any verbal consent, if it was given at all.
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According to Elaine Kusel, a lawyer who would later represent the Nigerian families involved, it wasn't. The subjects “had no idea they were part of any clinical trial.”
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Despite Pfizer's apparent inability to acquire written evidence of consent, the researchers didn't throw their hands in the air and jet back home. They moved forward with their experiment anyway.

Researchers are often convinced they are helping their subjects, whether the patients know it or not. In the end, Pfizer lost the same proportion of children in their Trovan group as their Rocephin group, around 6 percent.
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So, even with subjects later saying they were tricked into participating, the attitude of other Western researchers is cavalier. “I don't see the harm in it,” said
UCLA meningitis expert Larry Baraff of the study. “It sounds like they all did well.”
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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?”
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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.
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Nor did the agency have anything to say about the utter lack of evidence of participants' informed consent.
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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.
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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.
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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.
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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.
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Despite the 1979 Belmont Report's clear statement that human subjects must not be tempted into risky experiments by cash or other benefits,
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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.
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