Pharma

Roberto Abadie is an anthropologist who has studied the experiences of people who get paid by pharmaceutical companies to take drugs in clinical trials. For the past two years, he has been a visiting scholar at the public health program at the Graduate Center of the City University of New York. His book, The Professional Guinea Pig: Big Pharma and the Risky World of Human Subjects, was published by Duke University Press last year. Monica Gagnon interviewed Abadie by email for CHW. An edited transcript follows.

CHW: What inspired you to launch an investigation into the ethics of clinical trials?

RA: In 2001, Ellen Roche, an employee at Johns Hopkins University, volunteered in a clinical trial for asthma. She suffered an adverse event (as adverse drug reactions are usually referred to) fell into a coma, and died at a local hospital a month later. She had received a few hundred dollars for her participation in the trial that resulted in her death. I realized then that while bioethicists have been debating the ethics of paying volunteers participating in the first phase of clinical trials where drug safety is assessed, no empirical studies documenting the volunteers’ experiences and motivations to volunteer had been conducted. I was especially concerned about those volunteers who earn a living by selling their bodies to test drug safety. Some professional guinea pigs (as they refer to themselves) I met have done 80 or more trials in the course of a few years. I wanted to know how much they knew about the risks they face as trial subjects but also how the prospect of monetary compensation affects their perception and disposition to volunteer.

CHW: What challenges did you face during your research into Big Pharma? Did they attempt to shield their practices (or their human trial subjects) from you?

RA: Big Pharma is not a very open industry and they try very hard to shield information about their practices. Of course, they won’t say they don’t want the public to know. Their argument is that everything related to the drug production process is proprietary information. By being secretive they are protecting their products and their shareholders. It was very hard for me to gain access to the industry side. I wanted to ask them questions about how they deal with the issue of risk during the first phase of clinical trials and what they do to ensure that research subjects are adequately protected. Unfortunately, I didn’t manage to reach them. One of the public sources of information about Big Pharma’s practices regarding Phase I trials, or any aspect of drug development for that matter, are the lawsuits that are brought against them. For example, the Vioxx case went to court and its records provided a great deal of information about how the industry thinks about risks, public health and profits. Unfortunately, few cases go to court; most are settled out of court, leaving valuable information hidden from the public view. Professional healthy research subjects I met with feared retaliation from the industry if exposed, but anonymity protected them well.

CHW: How do the participants in the trials you studied now think about the pharmaceutical industry?

RA: I studied a very particular subgroup of the ample universe of subjects that earn a living as professional guinea pigs in America. I focused on a group of white, male anarchists living in Philadelphia, a hotbed of clinical trials activity. While all professional research subjects share similar interests (make money from participating in the trials) and experiences of dehumanization and alienation, this group of anarchist guinea pigs has particular strong views against Big Pharma and also, not surprisingly, about the role of the government and the FDA (the agency in charge of overseeing the drug production process). These volunteers feel that the industry lies, not only because they enroll volunteers when they know they don’t meet all their admission criteria, but more importantly, they lie to the consumers by producing drugs that are not safe and effective, as the industry claims.

But despite their hostility towards the industry, they feel the trials they participate in are in general only moderately risky. First, they reason, they are scientific, controlled experiments where there is a lot of oversight. Second, adverse events are very rare in their experience and most of them had not experienced them. And finally, they believe that ethical regulations and the fear of lawsuits are enough to deter the industry from bad practices.

CHW: How are the health risks of clinical trials underplayed by Big Pharma?

RA: I think that the most important risk overlooked by the industry is the risk derived from the fact that trials depend on a group of professional guinea pigs, paid to test drug safety. These subjects consider their trial participation to be their job, a particular kind of trade where boredom, pain and dehumanization are exchanged for money. They do seven or eight trials a year, deriving a total estimated income of $20,000 in a good year. The problem is that the industry does not have a registry that tracks trial participation and might not be aware of the extent of the professionalization.

My concern is that continuous participation in the trial economy might expose trial subjects to unknown or unforeseen risks, some of which might show up 20, 30 or even more years later. The industry is under a lot of pressure to recruit and retain trial subjects and has no incentive to create a registry or implement any measure that would limit their ability to recruit trial subjects for the first phase of clinical trials.

CHW: What are the economic forces that drive pharmaceutical companies to use risky test strategies?

RA: In particular, considering Phase I clinical trials where drugs are assessed for toxicity and not therapeutic benefit, Big Pharma depends on a group of professional subjects to run the trials smoothly. Until the 1970s, drugs were first tested on prisoners. Willing, compliant and readily available, they represented the perfect captive research subject. But ethical concerns brought the practice to a halt. The industry had to find a replacement population for an increasing number of trials and started paying prospective subjects. Some started volunteering and become dependent on the income and habituated to the trial routines.

Market recruitment of trial subjects created a new economic category: the professional guinea pig. It works well for poor, vulnerable research subjects because it provides a flexible schedule with reasonable pay, and it is great for the industry because it offers a steady supply of bodies to test drug safety quickly and effectively. The underside is that this professionalization might expose these workers to occupational risks, something that other workers in mining or agriculture have also experienced and where risks are better documented.

CHW: To what extent has the FDA addressed these problems?  What has limited their effectiveness as a regulator of testing practices?

RA: The FDA only audits one percent of Phase I trials in America. And it is a paper trail kind of process, looking for protocol inconsistencies and especially missing cases where subjects unexpectedly are dropped from the research protocol. Of course they also pay attention to the reporting of adverse events. But this monitoring has severe limitations. First, they review a very small number of trials. Second, they never do on site inspections, ­going to the trial sites, looking at the working conditions, talking to research subjects, etc. Part of the explanation for this lack of enforcement is that the FDA does not have enough resources and manpower to do this kind of job.

But the main cause is that the FDA increasingly, since the 1980s, has taken the view that what is good for the pharmaceutical industry is good for the public and that speeding the drug development process would be a good thing because first, it would bring valuable drugs to consumers, but also would help American companies compete better in a global pharmaceutical landscape.

CHW: What is the crux of the relationship between risk and monetary compensation? Do you find that volunteers typically fully understand the risks of participating in these clinical trials?

RA: The research subjects I studied are well informed about risks but this does not mean that they make good decisions about whether they should enter a trial or not. For example, they know that psychotropic drug trials are risky and they try not to volunteer for them. But this is one of the fastest growing sectors in drug development and a big producer of blockbuster drugs for the industry. Big Pharma needs to test the safety of these drugs, and knows that subjects are reluctant to mess up their mind, as they have told me, taking them. What would the industry do then? Simple, they just offer the highest pay, from $5,000 to $10,000 for a few weeks as a trial subject. Most subjects I interviewed admitted that they thought these trials presented a high risk but were tempted by the money and had done at least one.

CHW: Do professional guinea pigs often rely on money from test trials as their primary income? If so, why is this particularly problematic?

RA: They do. For most of them, trials are their main, and in many cases only, source of income. They can earn around $20,000 a year and sometimes even more. I find this practice extremely problematic because Big Pharma uses money strategically to recruit and retain research subjects who otherwise would have no interest in participating in the trial economy.  Research subjects are vulnerable because they depend on the income generated from the trial and that leads them to accept poor working conditions or risks they would not accept otherwise. Of course, the industry knows this and that’s why they use money to lure people and to keep them participating.

CHW: In what ways are the rights of human test subjects protected (or not)?

RA: Ethical regulations regarding the participation of human subjects in research have evolved a great deal since the horrors of the WWII. We have now a number of regulations that protect subjects like the requirement of informed consent before a subject enrolls in a trial. And civil law also affords protections against any wrongdoing or harm that occurs during the trial. Still, the consent form requirement is seen by professional guinea pigs as a formality, a paper to be signed among others in order to enter the trial. In most cases they make their decision about entering a trial before they get to sign the consent form. And legal recourse is expensive and might be out of reach for most subjects, unless they die or experience devastating adverse events, in which case the prospects of financial gain can lead skilled lawyers to volunteer in the case

CHW: Have you come across any particularly unique stories of people who have had negative (or positive) health effects from these trials? Please describe.

RA: There are no positive health effects from healthy research subjects testing drug safety in the first phase of drug development. These tests are designed to assess the toxicity of a drug, not its efficacy and thus no health benefits are expected. Negative health effects or adverse events are rare. While most of the subjects I encountered had experienced some discomfort, fainting, nausea or other symptoms, they had not faced serious adverse events. In 2006, a trial sponsored by Parexel in England left research subjects with very serious injuries and opened a public debate about the professionalization of Phase I trial research in Europe and the need to create a centralized registry to track participants involvement in this trial economy.

CHW: How do you suggest that Big Pharma change its practices and policies regarding human subjects?

RA: Since there is no centralized record tracking the participation of research subjects in Phase I trials in America, nobody knows for example if a subject is doing two trials at the same time, or if a subject is not complying with the mandatory 30-day wash-out period in between trials. As I mentioned in the previous question, such a registry was recently implemented in Europe when it was found that trial subjects in drug safety trials were trial hopping, doing for example a trial in Ireland, then another one in England, one immediately after in Germany and a subsequent one in France. A centralized registry would prevent this from happening in the US as well. Such control would slow the recruitment rate of research subjects, delaying the completion of Phase I trials, and that’s why Big Pharma has been opposed to its implementation.

CHW: What are the broader public health implications of this practice of the pharmaceutical industry, and what can be done about it?

RA: The lack of a centralized registry tracking the participation of professional research subjects in Phase I trials endangers the research subjects because it exposes them to dangerous drug interactions. But it also challenges the validity of the trial itself because its findings become compromised if researchers cannot tell with certainty that their results are not contaminated by a different drug that is being surreptitiously taken by the research subject, enrolled simultaneously in two different trials. This is a very serious development because it compromises the quality and efficacy of drugs millions of people depend on for their health care.

The lack of a centralized registry, but also of adequate FDA control regarding the first phase of clinical trials speeds up drug production and contributes to making Big Pharma one of the most profitable industries in America. But increasingly we find new evidence that the pharmaceutical industry’s continuous search for profits and public health interests are not on the same page. We need to step up the oversight on this industry, from government, of course, but also from citizens and consumer groups. In particular, journalistic exposes have contributed to documenting outrageous cases of abuse and exploitation of research subjects in Phase I trials, like the case of undocumented Latino immigrants being recruited in a facility in Florida a few years ago, or poor, African-American homeless men with alcohol and drug related issues recruited at a site in the Midwest. Such cases, when exposed through the press, generate a public relations nightmare for these companies. When they are touched in their pocket books, these companies have shown they can do the right thing.

Image Credits:

1.     Duke University Press

2.     epSos.de via Flickr

3.     AuntieP via Flickr

4.     Roberto Abadie

5.     MedIndia