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Medical Research for Hire: The Political Economy of Pharmaceutical Clinical Trials by Jill Fisher. Rutgers, 257 pp., £23.50, January 2009, 978 0 8135 4410 6 When Experiments Travel: Clinical Trials and the Global Search for Human Subjects by Adriana Petryna. Princeton, 258 pp., £18.95, June 2009, 978 0 691 12657 9 The Professional Guinea Pig: Big Pharma and the Risky World of Human Subjects by Roberto Abadie. Duke, 184 pp., £15.99, October, 978 0 8223 4823 8
he last few years haven’t been the best for the business of medical research. There was the Sanofi-Aventis researcher in California who was arrested waving a loaded handgun; police found a package of cocaine stuffed in his underwear. There was the psychiatric researcher in Oklahoma City whose medical licence was suspended after he infected two patients with genital herpes, and who was investigated by the FDA after he barred a research subject from leaving his clinical trial facility. In Miami, investigative reporters for Bloomberg Markets magazine discovered that a contract research organisation called SFBC International was testing drugs on undocumented immigrants in a rundown
motel; since that report, the motel has been demolished for fire and safety violations. Several pharmaceutical companies have been caught up in controversial cases of suicide, such as that of Dan Markingson, a young man who stabbed himself to death while taking Seroquel in an AstraZeneca trial at the University of Minnesota, and Traci Johnson, who hanged herself in a study of Cymbalta at the Eli Lilly trial site in Indianapolis. Britain had its own disaster at Northwick Park Hospital in north-west London, where six healthy subjects nearly died in a ‘first in man’ study of a monoclonal antibody. And Pfizer has spent longer than a decade dealing with the fallout of a study in Kano, Nigeria, in which 11 children died during a
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meningitis trial allegedly rigged to show that the antibiotic Trovan was superior to a competitor’s drug. The Trovan case has wound its way through various courts for years, generating millions of dollars in damages and a stubborn public relations problem for Pfizer. It is time for a ‘rebranding’ campaign, according to the Center for Information and Study on Clinical Research Participation. CISCRP is a non-profit group funded by pharmaceutical companies, academic health centres and contract research organisations. According to CISCRP, the public image of the pharmaceutical industry ranks alongside that of used-car dealerships and tobacco companies, and too often the media portray pharmaceutical research as ‘deceptive and evil’. So CISCRP has launched a new public relations initiative, called ‘Medical heroes can be found in everyday places.’ Funded by the pharmaceutical company Eli Lilly and orchestrated by Ogilvy Healthworld, the purpose of the initiative is to transform the image of the clinical trial volunteer from ‘guinea pig’ to ‘medical hero’. CISCRP has produced a slick public service announcement; it is sponsoring ‘clinical research education days’ all over America; and it is distributing posters, DVDs and shiny ‘Medical Hero’ badges to research subjects. Apparently the strategy is working: subject recruitment is up in areas where the campaign has run. Even bioethicists are pitching in. A team from the Department of Clinical Bioethics at the National Institutes of Health recently argued in the Journal of the American Medical Association that signing up for clinical trials is a prima facie moral duty
owed by every citizen. Over the past twenty years or so, without much fanfare, clinical research has undergone a remarkable free-market conversion. Until the early 1990s, most pharmaceutical research on human subjects was conducted by physicians in universities and teaching hospitals. (The FDA, which must approve drugs before they can be marketed, doesn’t conduct clinical trials itself.) However, pharmaceutical companies have been in search of cheaper, more efficient venues and today about 70 per cent of clinical trials take place in the private sector, often in the offices of private physicians or at dedicated sites. Clinical research has become a multibillion-dollar global industry, spawning spin-off businesses that barely existed 25 years ago, from patient recruitment firms and medical communication agencies to for-profit research ethics boards. The most important new players are contract research organisations (CROs) such as Parexel, Quintiles, PPD and Covance, which have built themselves into corporate giants by taking up the management of clinical trials. The research that many of us used to imagine as a humanitarian enterprise, carried out by selfless scientists and funded by Pink Ribbon campaigns and ‘Race for the Cure’ marathons, is actually a thoroughly Taylorised corporate system, outsourced and streamlined for maximum efficiency. It is striking just how little is known about the new clinical trials industry. Partly this is because it is so widely dispersed. Back in the old days, if you worked in a medical school or teaching hospital, you
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could often get a feel for a clinical trial simply by walking down the hall. Now you might need to go to India or Uzbekistan. Even if you restricted yourself to domestic studies, you would log a lot of miles trying to visit all the various stations in the production line. The trial itself might take place at fifty different sites, ranging from Ivy League teaching hospitals to a business park near Toronto airport. The ethics committee approval would probably come from Olympia, Washington; the subject recruitment could be managed in Dallas, Texas; and the trial results might be written up in Princeton, New Jersey. It is no wonder only industry insiders seem to know exactly what is going on. When Bloomberg reporters discovered that SFBC International was paying immigrants to be test subjects in a dilapidated former Holiday Inn in Miami, SFBC had recently been named one of the best small businesses in America by Forbes magazine. The Holiday Inn testing facility was the largest in North America, and had been operating for nearly ten years before inspectors noticed there was anything wrong. Lodged somewhere between the secrecy and the scandals is the work of a new generation of ethnographers who are quietly studying the way the clinical trials business operates. What interests Jill Fisher, Adriana Petryna and Roberto Abadie is not so much the occasional outrage uncovered by investigative reporters, or even the formal regulation of clinical trials. They are more concerned with the everyday pressures and moral choices facing the workers who man the production line: the private-sector phys-
icians who conduct the trials, the study monitors and trial co-ordinators who oversee them, and the research subjects who take experimental drugs, often in exchange for free medical care or a wage. What does clinical research look like when everyone is in it for the money? For a start, it looks a lot less like science. ‘I do not do original research; I do contract research,’ says a private physicianresearcher in Medical Research for Hire. A contract researcher does not come up with original ideas, or design research protocols, or analyse research results, or write them up for scientific publications. All of this is done by the pharmaceutical company or its hired specialists. What a contract researcher does is recruit subjects, monitor their clinical care and sign off on the paperwork. Not a lot of original work is done, and in some cases, not much work at all (a running joke has it that physicians do clinical trials in order to improve their golf games). The industry term for these nearabsent physicians is ‘phantom investigators’. Usually they will ‘come in on a daily basis, on most days, and they’ll sign off on all the things they need to sign off on, see any patients they need to see, and they’re gone,’ a study monitor says to Fisher. The researchers are usually on-site for no more than an hour or two a day. Contract researchers may not do much intellectual work, but this doesn’t mean they are not well paid. A part-time contract researcher conducting four or five clinical trials a year can earn an average of $300,000 in extra income. In 2000, a full-time clinical trial site earned an average of $1.6 million.
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According to Fisher, any given service will generate between two and five times as much money for a physician when a pharmaceutical company is paying the bill as when a health insurance company or a government agency is paying. Even an ordinary office visit will be paid at twice the usual rate if the visit is part of a research study. Some physicians sign up as contract researchers for the same reasons they might peddle nutraceuticals or dispense cosmetic Botox injections. It is a way to make extra money. owever, the most valuable commodity in the contract research business is not the physician. It is the patient: ideally, the sort of patient that the industry calls ‘ready to recruit’. Ready to recruit patients are sick people who can easily be persuaded to enrol in clinical trials, often because they are so poor that they have no better alternative. If a patient can be persuaded to enrol in a study quickly, so much the better: drug patents last only twenty years, and the patent clock ticks down while the drug is being tested. Four out of every five clinical trials are forced to extend their timelines because of recruiting delays. For years the demand for research subjects has been growing, driven not least by the sheer number of clinical trials being conducted in the desperate search for new blockbuster drugs. Nobody really knows how many trials the industry is currently conducting, but a WHO official estimates that 20,000 are initiated each year. They are getting larger and more complex, partly to
satisfy safety regulations, but also because many of the drugs being tested are so similar to drugs already on the market: if a new drug is only incrementally better than a control drug or placebo, demonstrating a statistical difference requires many more research subjects. The pool of potential subjects is gradually becoming depleted, in part because so many subjects in North America and Western Europe are taking other medications, which will often exclude them from enrolling in trials. Drug companies need ‘treatment-naive’ subjects, who, like the ‘ready to recruit’, are easier to find in the developing world. In 1991, only 10 per cent of clinical trials were conducted in emerging markets; by 2005, that figure had increased to 40 per cent. According to Adriana Petryna’s When Experiments Travel, the most popular place for new trial sites is Central and Eastern Europe; there are plenty of sites, too, in the Asia-Pacific region. Between 1995 and 2006, the highest annual increases in the number of active clinical researchers occurred in Russia, Argentina, India, Poland, China and Brazil. Many of these places have established a foothold in the industry as ‘rescue countries’: drug companies go there when they need data quickly – when their trials in the West have failed to show the drug is effective, for example, or when they have been unable to recruit enough subjects. Poland has been a popular place to test urology drugs and asthma drugs, a Czech physician tells Petryna; the Czech Republic has been a good spot for antibiotics and arthritis drugs. ‘There were treatment-naive, steroid-naive, statin-naive
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people – people you could hardly find in the US or Western Europe,’ the physician explains. ‘We had extremely high recruitment rates.’ The move into Eastern Europe began with the ‘opportunity’ phase, or the gold rush, when the trials industry first discovered the rescue countries. In the early post-Soviet years, clinical trials were easy to launch. ‘No one cared about the content of the investigations,’ the Czech physician says. ‘Ethical approval was a mere formality.’ There followed a ‘normalisation’ phase, when the trials became a routine, accepted part of healthcare. Over time, patients no longer saw them as experimental, but as part of their standard medical treatment. Finally came the ‘exhaustion’ phase. Too many companies were competing for subjects; the subjects began to get choosy; regulations began to tighten. So the clinical trials industry began to move further east – to Russia, for example, Ukraine, Uzbekistan and Kazakhstan. The move to poorer countries intensifies the ethical problem created by a marketbased trial system. The patients have even less access to standard medical care than patients in the US, and by enrolling in trials they can get drugs that they could not otherwise afford – never mind that the drugs are experimental, or may be placebos. Physicians who are paid handsomely to recruit their patients for trials will often find the money hard to resist, since they make so little practising ordinary medicine. ‘In Russia, a doctor makes $200 a month,’ a contract research executive tells Petryna, ‘and he is going to make $5000 per Alz-
heimer’s patient.’ Contract researchers may find that their sponsors do not welcome bad news about the trials, especially if the drug appears unsafe. Reporting that subjects have experienced a ‘serious adverse event’ (industryspeak for the worst side effects) may mean losing the contract. One physician told Petryna she had done a clinical trial on a drug that appeared dangerous, but when she documented her concerns and recommended redesigning the trial, the sponsor ignored her and successfully submitted the drug for approval. The drug was later withdrawn from the market. ‘We never got a contract from that manufacturer again,’ she adds. Financial incentives present a different ethical problem for a Phase I trial, the purpose of which is to determine if a drug is safe. Most Phase I trials are done on healthy subjects. Until the mid-1970s, this usually meant prisoners; today the trials are done mainly on the poor, who sign up for the money. Not just any poor person will do, though. Ideally they should be between the ages of 18 and 45 and in good health, or at least good enough to pass the screening tests, and they should not be taking any drugs other than the ones they are testing. Most important, they need to be available to check into a testing facility for up to several weeks at a time, where they will eat, sleep and endure a daily routine of blood draws, urine tests and invasive medical procedures. It isn’t hard to imagine the sort of people that make up the bulk of Phase I trial subjects: the unemployed, immigrants, contract workers, university students, ex-
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cons and anyone else with a reason for working off the grid. Some people even manage to make a living as professional guinea pigs, travelling from one trial site to another for years. One guinea pig pro describes it to Roberto Abadie as the ‘mild torture economy’. The issue of payment has always worried regulators and ethicists, who are concerned that excessive fees will tempt impoverished subjects to take risks with their health. Nevertheless, the amount of money offered to subjects has, over the years, gradually crept up. At the low end of the pay scale are ‘bioequivalence trials’, or what guinea pig pros call ‘bleed and feeds’. These studies compare standard FDA-approved drugs at the end of a patent cycle with their generic equivalents; they pay the least because they are seen as the least risky. The most lucrative studies are longer trials testing the safety of new drugs, with lots of in-patient time and plenty of unpleasant medical procedures. These sometimes pay subjects upwards of $6000. (One recent study sponsored by Nasa offered subjects $17,000 to lie in bed for 60 days, not to test a drug, but to study the effects of microgravity on the human body.) The range of subjects eligible for payment has also expanded considerably. Several years ago, most trial sites paid only healthy adult subjects. Now some sites pay parents to enrol their children. Many also pay subjects who are sick, especially subjects with milder chronic illnesses such as asthma, or whose metabolism is impaired by kidney or liver disease. A study currently being advertised in St Paul, Minnesota, near where I live, is testing a drug
on patients whose kidney function is so badly compromised they are on dialysis. The sponsors will pay patients $2525 to take part, as long as they are willing to spend four nights at the test site and come back for eight out-patient visits.
erhaps the most fertile guinea pigging territory in the United States is the region around Philadelphia, which is home to a number of medical schools, pharmaceutical companies and clinical trial sites. For his work on The Professional Guinea Pig, Abadie lived in an anarchist community in West Philadelphia, many of whose members enrol in trials to fund their work as artists and activists. These trial subjects have few illusions about the value of what they are doing or why they are doing it. ‘They pay you just to demean you to animal status,’ one seasoned trial subject says. A Latino man with the pseudonym KingLabRat says he began enrolling in studies in the mid-1980s after he was discharged from the army, allegedly for beating up his sergeant. In between trials he sells drugs and works in a morgue. ‘It’s for the rent-use of your body and the inside operating fluids,’ he explains. ‘That’s it pretty much in a nutshell.’ KingLabRat has been injected so many times he has scars up and down his arms, which he regards as badges of honour. Guinea pigging may have become a job, but it does not carry many benefits. Research subjects do not have the right to workers’ compensation, health insurance or a minimum wage. Trial sites are not regulated in the same way as workplaces. If
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subjects are harmed by the drugs they take, they have no right to compensation, and they may well have to pay their own medical expenses. According to a survey published in the New England Journal of Medicine, only 16 per cent of the policies issued by academic health centres in the US offer free care to research subjects injured in trials. Litigation, the usual American substitute for regulation, is not really an option for most guinea pigs, at least not if they want to continue doing trials; just a whiff of defiance can be enough to get a subject banned from a research site. Robert Helms, a veteran of more than 80 trials who founded a jobzine for research subjects in the mid-1990s called Guinea Pig Zero, compares guinea pigging to prostitution. ‘They are penetrating your body,’ Helms says. ‘You are renting out your body and they don’t care about what you are thinking.’ Many of the guinea pigs in West Philadelphia are anti-corporate political activists who take the easy money on offer instead of signing up for a nine to five job. Yet because they don’t buy into the ‘medical heroes’ propaganda of the clinical trials industry, they have no incentive to take the job seriously. ‘I even try to sabotage the results now and then,’ one subject tells Abadie. ‘I am pretty cynical and don’t think that the trials result in much medical benefit.’ These activists take up guinea pigging because it allows them a measure of distance from ordinary corporate capitalism, yet it is only by virtue of their participation that the system can work. None of these ethnographers appear to place much confidence in the system’s cur-
rent means of protecting human subjects. There is a heavy reliance on the informedconsent forms that subjects are expected to sign, but as Fisher points out, most subjects have already made up their minds to enrol in a trial before they even see the form. Institutional review boards, the quasi-regulatory bodies charged with overseeing the ethics of clinical trials, are often for-profit companies paid by the sponsors of the research they are evaluating. If one review board says a study is unethical, the sponsor can simply take it to another one. No wonder some subjects feel as if they are on their own. As Helms puts it: ‘The authorities, the regulators, the courts, they are not there to protect you if you are workingclass or a guinea pig, anybody at the low end of the totem pole.’ By turning clinical research over to the market we have created a system in which private physician-investigators can make far more money persuading their patients to enrol in research studies than by simply treating their illnesses; in which patients sign up to test new drugs, either because they need the money or because they have no way to pay for ordinary healthcare; in which investigators are financially punished for telling companies that their drugs are risky or dangerous; and in which even ethical oversight has become a revenue-generating mechanism. Lost in this business model are the human research subjects themselves. As a CRO manager in Eastern Europe tells Petryna, apparently without irony: ‘We don’t c see patients, we see data.’
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