Tuesday, March 8, 2011

Medical Research for Hire by Jill A. Fisher

The ethics of medical testing is a topic of great current interest. The recent revelation of unethical human experiments by U.S. scientists in Guatemala in the 1940s has brought focus to this issue. The Associated Press (AP) produced a review of the practices that were at one time common. President Obama has designated a bioethics commission to provide him with feedback on the issues involved in the Guatemala situation and any concerns with overseas testing that might be occurring today. A report is due by September of this year.



A review of Jill A. Fisher’s book, Medical Research for Hire: The Political Economy of Pharmaceutical Clinical Trials (2009), is particularly timely.


Fisher includes details of past medical practices and discusses much of what was contained in the AP article. She covers the subject quickly because her interest is not in the past, but in current practices. This quote will describe the surprising and frightening approach to medical ethics that was rampant throughout the scientific community.
“State institutions, such as mental institutions, orphanages, and prisons, have....been a locus of medical inquiry because researchers saw their occupants as convenient, captive populations. In the case of mental institutions, the belief in the biomedical community during the first half of the twentieth century was that if a person was unable to give true consent, that person could be used in research without even being asked. This assumption implied that if individuals were not able to function ”normally” in society, their bodies were rendered property of the state, mental institution, and/or medical research facilities.”
Research using inmates at prison facilities provided a precedent that in many ways previews the current system.
“By the 1960s, medical experimentation was deeply integrated into the penitentiary system, such as military research on LSD, radiation studies, and diverse pharmaceutical trials....prisoners were often paid for their participation or were offered a reduction in their prison sentence; wardens and parole boards viewed prisoners’ participation in research favorably.”
It would appear that the prisoners gave their consent for these experiments on their bodies. Fisher would argue that providing such incentives to a disadvantaged population does not meet the standards of “informed consent” that are required. She would also claim that a similar situation persists today with the role of prisoners being taken up by the poor and those with no access to normal medical care.


Before 1990 most pharmaceutical research was carried out in academic centers. The academic approach was deemed too slow and too inefficient in recruiting new participants for the testing. Since then, the research has been outsourced to what has become an enormous industry.
“In 2004, pharmaceutical companies spent a record-high $49 billion on research and development (R&D) of new products, which is a reported 19 percent of industry sales from the same year. Approximately $15 billion of that budget was used for clinical trials.”

“Currently, about three-quarters of studies in the United States are conducted in the private sector by nonacademic physicians who recruit their own patients or local community members into drug studies. Over 60,000 of these studies take place in the United States each year, accounting for 75 percent of the 80,000 of the clinical studies conducted worldwide; to execute these studies, more than 50,000 U.S. physicians registered with the Food and Drug administration (FDA) as principal investigators on one or more clinical trials in 2001. As for human subjects, 3.62 million Americans participated in pharmaceutical clinical trials in 2003 alone.”
This sub-economy is driven by the desire of drug companies and doctors to maximize profits or income, and on the human subject side by the lack of income or lack of access to medical care. Do 75 percent of the drug trials take place in the U.S. because we have the greatest supply of poor people without healthcare coverage in the industrialized world? Quite likely so.


Fisher is not concerned directly with the efficacy of this method of testing drugs for human consumption—her concerns are ethical. Throughout this system, from human subjects to drug companies, there are ethical issues related to the for-profit nature of the enterprise.


The author provides two charts that help illustrate the structure of this clinical testing economy. The first defines the different categories of tests.





Who are the participants in these studies? Fisher summarizes.
“Efficacy studies that test the effects of investigational products on patient-subjects’ illnesses attract primarily white middle-class women. Studies of this type that target relatively benign (that is, not life-threatening) illnesses attract mostly uninsured individuals, the majority of whom are also white women. In contrast, however, healthy subject clinical trials that test the safety of individual products and pay large stipends to volunteers attract mostly low-income minority men. In the Southwest, these studies are filled predominantly by Hispanic, non-English-speaking men, whereas in other parts of the country, these studies are filled predominantly by African American men.”
The reasons why these particular groups are overrepresented in the various cases is complex and well covered by the author. Of interest here is the process by which the poor and the uninsured are preferentially represented. In fact, there is a tendency for many in the healthy subject trials to be repeat participants. There are people who take part in a study, collect their money, wait for the medicines to be purged from their bodies, then sign up for another. This is a form of medical prostitution if you wish.


The second chart provides an outline of the industry structure.





This type of organizational structure is not surprising given the number of trials being run each year. There are more than the drug companies can manage without hiring a large number of dedicated employees. It makes more sense for them to outsource the responsibility. This also allows them to pass on the liability for any problems that might ensue. Contract Research Organizations (CROs) have arisen to fill the need of replacing the drug company as the trial organizer and monitor. Recruitment of subjects is often the critical path. It is not surprising that companies would arise to specialize in that function.


Everyone participating in this clinical testing economy is in it to earn a profit. Fisher has valid concerns that no matter how well regulated or monitored, this for-profit character invites unethical behavior.


There is no alternative to the current path for a drug company to win approval to dispense a drug. The trials put subjects at risk so one would hope the danger is worth the benefit. Yet, many of the current trials are not aimed at providing breakthroughs. Often they involve look-alike drugs that are being developed only to try to capture someone else’s market share. These are often the most expensive because it is known that no major effect will be seen. Small effects require good statistics and large numbers of participants. Is it ethical to put so many at risk for a gain in profit, but no medical benefit?


Many doctors give up their practices entirely in order to “lead” these studies. They can make much more money doing this than tending to patients and their only function is as a figure head who signs off on the work performed by lesser-paid staff. The ethical issues arise when they participate in clinical studies and also recruit patients for the studies. They will be under tremendous pressure to deliver subjects for testing as soon as possible. When a doctor sees a patient who has medical condition that is being addressed in an upcoming clinical study he/she has to make the choice of suggesting a standard/current treatment or suggest this trial as a means of treatment. The doctor would probably make more money with the patient in the clinical trial. He/she also knows that there is a finite probability that if the clinical trial is suggested it is possible that the patient would end up receiving a placebo and getting no care at all. Patients tend to trust their doctors. Fisher is concerned that this is asking too much of our physicians to expect them all to handle this situation appropriately.


Fisher’s description of the nurses and other assistants who actually work with the subjects, both in signing them up for the study and monitoring their condition throughout, depicts hardworking individuals who try their best to carry out their duties as they are defined. Their ethical conflict arises from the fact that they appear to be giving care to the participants as patients, but, in fact, they are representatives of the drug companies. A seriously ill subject whose health is degrading through the course of the trial may be receiving a placebo or may just not be reacting well to the drug. As a representative of the drug company it is their duty to try and maintain all participants in the study for the duration. Many of those who run these studies have a nursing background which provides the tendency to worry about the health of the subject first. This is a continual conflict of interest which many have trouble dealing with. As Fisher emphasizes, many subjects are attracted to these trials because it is their only way to obtain any kind of treatment. They tend to forget, or never realize, that they are not patients. They are data points.


The ethical posture for this process rests entirely on obtaining informed consent from the subject before proceeding. This involves having someone sit with the prospective subject and explain the risks involved, the procedures that must be followed, and the possible benefits. Fisher’s experience in observing this process is that, while it follows the letter of the law, it is flawed. Most subjects arrive having already decided to participate and show little interest in what is often a long and complex legal document. Few studies have potential side effects frightening enough to scare people away so the representative briefing the subject actually tends to use the time to inculcate in the subject a sense of responsibility for following procedures properly. The goal is to convince the subjects that they are contributing to the advancement of science rather than just following the will and whim of the drug company.


Fisher’s detailed exposition does not serve as an indictment of the drug trial industry, but it does serve the purpose of focusing on some of the ethical and moral issues involved. The most troubling concern is that this system seems to depend on having a ready supply of the poor and the healthcare deprived to exist. And who would have expected that there would be a herd of medical prostitutes out there selling their bodies for use by drug companies? The dual role of physician/study recruiter also seems ready for some scrutiny by the American Medical Association—at least.


When one recalls that about 3 million people in this country are involved in these tests, about one percent of the population, one has a nagging suspicion that something is radically wrong. Can all these tests really be necessary? With all that money being spent why are we not seeing better results? Are the pharmaceutical companies in the business of improving health or selling pills? We know the drug companies have admitted to criminal misuse of their products after FDA approval; can we trust them to behave ethically in the pre-approval process?


We need someone to perform a different kind of research and to write another book to answer those questions.

1 comment:

  1. Excellent post. My review is:
    Lindsay Rosenwald http://www.lindsayrosenwald.com/lindsay-rosenwald-director-republican-jewish-coalition/ Lindsay Rosenwald – Director Of Republican Jewish Coalition

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