Read an Excerpt
THE PROFESSIONAL GUINEA PIG Big Pharma and the Risky World of Human Subjects
By ROBERTO ABADIE
Duke University Press Copyright © 2010 Duke University Press
All right reserved.
Chapter One GUINEA-PIGGING The In/Formal Economy of Phase I Clinical Trials in Philadelphia
Phase I clinical trials employ healthy human volunteers to test new drugs under development by the pharmaceutical industry, not for therapeutic efficacy but for drug safety. Phase I trials are designed to assess the safety of the drug or compounds being tested, and represent the first time a chemical compound is tested in human beings after having been tested in laboratories and then in animals. After a drug proves its safety in phase I it goes through phases II and III, which involve larger groups of volunteers. While phase II also continues to test the drug for safety, this phase and the next one are intended to test for therapeutic benefits. If the drug proves safe and therapeutically efficacious, it then receives FDA approval and goes on the market.
Phase I clinical trials are designed as controlled experiments that follow an experimental design. The trials are devised to obtain information about how the human body responds to a particular substance, what the levels of toxicity are, and how the drug is absorbed and eliminated. As previously mentioned, this phase is not designed to test therapeutic effects on the volunteers. It is for this reason that the trials have also been described as "non-therapeutic" in contrast to the "therapeutic" trials in phases II and III.
RECRUITMENT, RETENTION, AND PROFESSIONALIZATION OF HUMAN SUBJECTS
Clinical-trial researchers need to recruit volunteers to carry out trials. A healthy population is an indispensable requirement of the experimental design employed in randomized clinical trials (RCTS) used in phase I clinical-trials research.
A healthy and homogeneous trial population would ensure that all participants have the same condition at the outset, making it easy to attribute the outcome of the experiment to the drug regimes to which the volunteers are exposed. Therefore, the lack of any existing medical condition is an indispensable requirement for the realization of any clinical trial. Phone interviews screen medical histories, as do further screenings to select the candidates and again at the beginning of the trial. A healthy population also contributes to minimize risks among volunteers by eliminating potential drug interactions with existing medical conditions.
Pharmaceutical researchers not only need to recruit a sufficient number of healthy volunteers to conduct trials but need to do so quickly. The more time they expend in finding the volunteers they need, the more they delay their scheduled experiments. Delays are costly and add to overall research expenditures. Obtaining the right number of volunteers but with the wrong qualifications also puts the trial's outcome at risk, seriously compromising the volunteers' health and the validity of the trial. But recruiting the right number and the right kind of volunteers is no easy task. That is why in recent years there has been a shift in the way phase I trials are conducted. While some pharmaceutical companies still run their own trials, most have been outsourced to universities, or to independent contractors known as CROS.
During phase I the professional knowledge required in drug development is mostly supplied by biostatisticians and experts in toxicology. In contrast to later phases in drug research, no specialized knowledge about a particular disease or medical condition is required, making the task of outsourcing easier. Speed, flexibility, and the ability to recruit a large number of volunteers are the usual presentation cards for aspiring CROS. Their functions are broad, from recruiting volunteers and gathering data to ensuring ethical oversight of the trials with the help of a usually friendly ad hoc IRB.
In an open, competitive market, CROS compete among themselves, trying to lure the best research subjects they can find. In recent years increasing competition to attract subjects in high-demand areas has led to a surge in the amounts paid to volunteers. But financial inducements are only part of the package offered to prospective subjects. Instead of the prisonlike environment offered ten or more years ago, now there are individual suites, Internet access, flat-screen televisions, and even pool tables, among other amenities. Food has also improved, along with a more professional and "respectful" staff. Because of their anti-consumerist tendencies anarchist guinea pigs are not generally appreciative of fancy sites, which usually involve a large number of trial subjects and rotating personnel. Many told me that these sites look like factories, large and impersonal, furthering their sense of alienation. They prefer trials at Jefferson, an academic hospital with a very friendly and stable staff but less glamorous facilities, and some guinea pigs, like Helms, had volunteered only there in recent years. KingLabRat and the Canadian Guinea Pig, in contrast, found large sites like those of GSK very nice and volunteered there quite often. Of course investments in amenities are only made where they are really necessary to attract or retain paid subjects. In remote areas, such as parts of the Midwest, where demand for volunteers is not as strong and paid subjects have fewer choices, trial conditions are not as good.
A glimpse at just a few of the hundreds of advertisements published in weekly newspapers in Philadelphia, or posted at recruitment sites at the major pharmaceutical companies operating in the area, summarizes industry requirements for phase I clinical trials. Subjects must be healthy males eighteen to forty-five years old with flexible schedules. The companies over "financial compensation for time and travel expenses" or, more directly, invite the volunteer to "make money" by joining a trial. It is not hard to see the gender bias in pharmaceutical research. In phase I clinical trials males have historically been the preferred human subjects and remain so. The gender bias in recruiting volunteers is not lost among paid female volunteers: "When I started doing trials they were not for women at all and I remember that a doctor told me that recently had been a study at that place for a breast cancer medication and the volunteers were all men. I asked why and she said it was because the pharmaceutical industry still thinks of men as normal humans and women as aberrations. Women have abnormal bodies because they are not men, men are the norm. Now most of the trials if you are sterile women can do them, so I think that this is their main concern with it" (Cidar House Girl, 12 June 2004).
Since the level at which an experimental drug becomes toxic is unknown-that is precisely what a study is to determine-the pharmaceutical industry fears that experimental drugs might affect fertility and pregnancy outcomes in women who volunteer for phase I trials, exposing the industry to lawsuits. Despite this, the pharmaceutical industry has been encouraged in the last decade to incorporate a more diverse population in trials. Still, while women have been included in phase I trials research, they are a very marginal population. Most of the trials enroll only men and just a few recruit both men and women. Trials intended to assess the toxicity of contraceptive drugs or other products devised for women's use employ female volunteers, which is no doubt an advance if we consider-for example-that the birth control pill was originally tested in men.
DEMAND FOR HEALTHY BODIES
Toxicological trials are not seeking just any men but "healthy" men. Again, the recruitment ads give us some clues: "not smoker," "drug-free," "non-congenital conditions," "takes no medication." The pharmaceutical industry goes to great lengths to make sure that the volunteers recruited for phase I trials are "healthy" and thus appropriate research subjects. Phase I trials depend not only on recruitment but also on retention. If someone withdraws from a trial before it is complete for whatever reason, the validity of the trial may be compromised. In sum, market recruitment ensures the availability of the large number of subjects the industry needs to perform phase I clinical trials while also contributing to the correct operation of the trial.
Professional volunteers are aware of the key role that they play in ensuring that clinical trials are run smoothly:
Well, the biggest thing with a clinical trial is that it's a poker game. The clinical trial wants a specific person with a specific profile that doesn't exist. They know it; guinea pigs know it and people don't talk about it. They want a person that is very healthy, has an open schedule, under a certain weight but does not exercise. A lot of times they ask you not to exercise because that messes up with the trial but then they want you to be under certain weight. The perfect volunteer they require doesn't exist. Everybody lies about complying and that's the biggest thing. I lied about my family medical history, yeah, about drug use, taking medicine. They have a lot of pressure to recruit enough people. The recruiters are under a lot of pressure to recruit, they need people. And also, once they found you too, they want you to continue. Once you showed dependable, you did the study and went through the whole thing, when they need to do a blood draw your veins work, you pee when they tell you to pee, never complain, once they have that they want to keep you. (Spam, 28 July 2004)
Paid volunteers are well aware of the demand for an idealized, perfectly healthy volunteer. They also realize that their body is a valued commodity in clinical trials research. Certainly, as Spam observes, it is not an abstract body that is sought and rewarded in phase I trials, but a well-trained, disciplined, and complying body-or subject.
There is no clear guinea pig career. Some volunteers started their career by selling blood or modeling for art schools, or doing less invasive procedures such as MRIS. Others jumped right into trials. Most guinea pigs have done exclusively trials or moved quickly into trials. This trajectory seems to support the idea that blood, semen, and other body fluids are not as valuable as body as a whole.
Financial compensation plays a central role in recruiting and retaining volunteers. The payment is scheduled to maximize the chances of ensuring compliance with the research protocol among volunteers. Generally it takes at least two or three weeks from the first phone interview to the time a trial begins. It is not until the first leg of the trial is over, or the whole trial if it is a short one, that the volunteer gets paid. Volunteers leaving the trial before the first leg of the trial is completed do not receive any payment, unless they can prove that they are experiencing serious adverse affects as a consequence of their participation. Since the object of the trial is to study the toxicity of the drug, side effects are expected, and therefore volunteers may have a difficult time negotiating their paid discharge with the trial staff. If the volunteers are successful in making their point, then they get paid based on the number of days they stayed in the trial.
There are a number of ways the industry promotes professionalization among human subjects volunteering for their clinical trials. All major research sites in metropolitan Philadelphia have a database of previous volunteers from which they draw when they need to fill a new trial. Potential volunteers regularly receive announcements of forthcoming trials. Registered volunteers can also check the industry's web site for trial opportunities. Some, like Michael, make occasional phone calls to inquire about possible trials and to let recruiters know about their availability. Most research sites over financial incentives for referrals, usually from $50 to $100. After a new volunteer finishes a trial successfully the volunteer who referred him gets a check. Eager to fill slots, research sites attempt to recruit volunteers for forthcoming trials even before a clinical trial is over. Currently volunteers are required to wait one month after they have finished a trial before submitting to screening in a new trial, but participants usually receive "invitations" for screenings in future trials once the waiting period is over. This waiting period is intended to "wash out," or eliminate, any trace of a drug from an earlier study. Yet only a few days after a drug has been taken it usually cannot be detected in a blood test. Some people who participated in trials in the early 1980s-when regulations imposing a waiting period between trials were almost nonexistent-remember that even before finishing one trial volunteers were invited to screen for a forthcoming trial and if accepted were enrolled right away.
A PROFESSIONAL GUINEA PIG TRIAL'S JOURNEY
"I needed money and some friends that do trials told me about this one coming. My friend told me that I should sign up because it paid really well for not having to do a lot. It turned out that the drugs weren't too risky and so for the money that you were making it was a pretty safe bet." That's how Michael, my roommate at Fancy House, described how he entered his last trial, just a couple of days after I moved there in early February 2004. He was a twenty-five-year-old white Kansan who had moved to Philadelphia and to Fancy House, one of dozens of radical, anarchist communes in the West section of the city at that time.
Although Michael had a degree in art design and did occasional under-the-table commissions designing jewelry and clothing for some friends in New York, this was not his main source of income. He had been a bike messenger first and later worked in the kitchen of a catering firm. When I met him he had just cut one side of his right thumb while operating a slicing machine. The cut was deep and painful, the kind of wound that made it impossible to stitch. Having no health insurance, Michael dealt with it by washing the site with disinfectants and removing the bandages from time to time. He missed a couple of days at work and then went back to his catering job, but not for long. He had earlier volunteered for a clinical trial, and two weeks before his accident with the slicing machine he had called one of the oldest medical schools in the city to find out if there were any clinical trials for which he could volunteer. He called not once but twice. As he told me: "You have to keep calling until they know who you are. They have a lot of people interested. I gave them the names of two people that I knew who were regular trial participants there. That helped me out."
The trial comprised two six-day periods with a washout period of ten days in between. For the duration of the trial Michael would need to comply with some restrictions, including prohibitions against drinking grape juice or exercising heavily, because these activities interfere with the drug regime. Michael's trial is a typical double-blind placebo trial, or randomized clinical trial (RCT), in which participants are randomly assigned to different groups that are administered different drug regimes. He had been placed in one of six groups receiving a combination of placebo and different drug regimes varying from 0.4 mg to 10 mg, and he would not know which drug regime he would receive. To test the safety and efficacy of the drug, he would get a tetanus vaccine and then have a biopsy performed to assess the anti-inflammatory response. Michael would have a total of five biopsies during the trial.
Excerpted from THE PROFESSIONAL GUINEA PIG by ROBERTO ABADIE Copyright © 2010 by Duke University Press. Excerpted by permission.
All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.
Excerpts are provided by Dial-A-Book Inc. solely for the personal use of visitors to this web site.