Carl Elliott
Adverse Events: Race, Inequality, and the Testing of New Pharmaceuticals by Jill A. Fisher
Adverse Events:
Race, Inequality, and the Testing of New Pharmaceuticals by Jill A. Fisher.
NYU Press, 319 pp.,
$89.00; $30.00 (paper)
When will we get a vaccine? That’s the question Americans have been asking since the novel coronavirus shut down much of the country in March. Dr. Anthony Fauci says it could happen this year. Others think it will take a lot longer. The HPV vaccine took fifteen years to develop. The chickenpox vaccine took twenty-eight. No widely effective vaccine has ever been developed for many life-threatening viruses, including cytomegalovirus and HIV.
One potential way to speed up the development of a vaccine for Covid-19 is a “challenge study,” in which researchers give healthy subjects a prospective vaccine and then infect them with the coronavirus. In conventional trials researchers typically give subjects either a test vaccine or a placebo and follow them over time in their ordinary living conditions to see if the vaccine is effective. But there’s no need to wait for a naturally occurring infection in a challenge study, which allows it to be shorter and to require far fewer subjects. Yet such a study would also require deliberately giving those subjects a potentially deadly illness for which there is no good treatment, and for some observers, that’s a deal-breaker. A joint statement by the AIDS Vaccine Advocacy Coalition and the Treatment Action Group says, “Until there is an approved treatment, a challenge trial with a potentially fatal and as-yet untreatable pathogen is unacceptable.” Nonetheless, the drumbeat for Covid-19 challenge studies is growing louder, and some of the most energetic drummers are bioethicists. Nir Eyal, a bioethicist at Rutgers, was one of the first to call for them.1 His proposal, cowritten with the epidemiologists Marc Lipsitch of Harvard and Peter Smith of the London School of Hygiene and Tropical Medicine, appeared online in late March. Challenge studies have also been endorsed by the NYU bioethicist Arthur Caplan and the vaccinologist Stanley Plotkin.2 Julian Savulescu and Dominic Wilkinson, bioethicist-physicians at Oxford, have raised the moral stakes even higher by proposing not just that researchers conduct Covid-19 challenge studies but that the first human subjects could be elderly nursing home patients. “Their motives might be purely altruistic,” Savulescu and Wilkinson wrote. “Or they may be fatalistic or wish to die, or at any rate not care if they die sooner rather than later.”3
1Nir Eyal, Marc Lipsitch, and Peter G. Smith, “Human Challenge Studies to Accelerate Coronavirus Vaccine Licensure,” The Journal of Infectious Diseases, Vol. 221, No. 11 (June 1, 2020). 2Stanley A. Plotkin and Arthur Caplan, “Extraordinary Diseases Require Extraordinary Solutions,” Vaccine, Vol. 38, No. 24 (May 19, 2020).
3Julian Savulescu and Dominic Wilkinson, “Extreme Altruism in a
The utilitarian argument for challenge studies is straightforward: calculate the number of lives risked and compare it to the potential number of lives saved. Backers of challenge studies point to a study (based on data from China) that estimates the risk of death from Covid-19 for a healthy adult between the ages of twenty and twentynine at 0.03 percent.4 And if subjects are recruited from hot spots where the risk of getting Covid-19 is very high anyway, they argue, infecting them deliberately wouldn’t put them at much greater risk. At least in a challenge study their medical condition would be closely monitored.
Challenge studies are troubling, of course, because many of us recoil at the thought of infecting healthy human subjects with a pathogen. But such studies are not unusual. Nor are they limited to the annals of past research abuses such as the Guatemala syphilis study in the late 1940s, in which US Public Health Service workers gave syphilis and gonorrhea to Guatemalan prisoners, soldiers, prostitutes, and psychiatric patients.5 Not only have infectious disease researchers in the modern era intentionally infected people with pathogens ranging from influenza to malaria and cholera, but they have done it with the approval of institutional review boards charged with protecting human subjects. Defenders of challenge studies argue that there is nothing wrong with infecting subjects as long as they have consented, the risks are minimized, and the studies are held to the same established ethical standards as others are.
Pandemic,” Journal of Medical Ethics Blog, April 23, 2020.
4Robert Verity, Lucy C. Okell, Ilaria Dorigatti, et al., “Estimates of the Severity of Coronavirus Disease 2019: A Model-Based Analysis,” Lancet Infectious Diseases, Vol. 20, No. 6 (June 1, 2020).
5Presidential Commission for the Study of Bioethical Issues, “Ethically Impossible”: STD Research in Guatemala from 1946 to 1948 (September 2011).
Many people are convinced that Covid-19 challenge studies should proceed. Thirty-five members of the US House of Representatives have called for them. The World Health Organization has not explicitly endorsed challenge studies, but it has published guidelines for how they might be ethically conducted. Among the strategies the WHO recommends to minimize risk to the initial subjects is to expose them to the virus “one by one, with meticulous titration of viral dose.” Some scientists worry that a small study may not reveal all the potential side effects of a vaccine, and that the results of a study on young healthy people may not be relevant to older, less healthy patients. Nevertheless, a website for a nonprofit group called 1DaySooner says it has signed up over 26,000 volunteers for Covid-19 challenge studies.
A useful comparison is Phase I drug trials, which are usually conducted to determine if experimental drugs are safe. As in challenge studies, researchers in Phase I trials intentionally expose their subjects to potentially serious risks not in exchange for any potential benefit to the subjects themselves but rather for the advancement of scientific knowledge. Research sponsors typically pay subjects between $200 and $250 a day to check into a locked research unit for several weeks while they are given an experimental drug. Researchers usually monitor their blood, urine, and vital signs, and some studies require invasive procedures such as lumbar punctures, biopsies, or endoscopies.
Because Phase I trials are such a routine part of drug development, bioethicists and social scientists have subjected them to far more scrutiny than challenge studies. In Adverse Events, the sociologist Jill Fisher has provided the most thorough examination yet.6
6I am a member of the advisory board for a National Institutes of Health grant for which Fisher is a principal investigator, and I have provided a quote for the book cover.
What can we learn from the way these trials are done?
Until the late 1970s most Phase I trials were done on prisoners.7 Today they are done mainly on poor people. A subject Fisher calls “Bob” was unemployed and on probation in St. Louis when he began doing paid studies at Washington University. They didn’t pay much, and some of them were grueling. One required him to ride a stationary bike with an endoscopy tube down his throat. When his probation ended, Bob began traveling around the country doing better-paid studies and competing in poker tournaments. By the time he spoke to Fisher he had done drug studies in seventeen different states. “That’s my golden vein,” he said, pointing to a scarred hole on his inner elbow where his blood had been drawn. “You can see I got, you know, a cavern there. Been stuck many times.” Like prisons, poultry processing plants, and funeral homes, Phase I trial sites occupy a segment of the American economy that is not so much hidden as overlooked. If the world that Fisher reveals in Adverse Events is unsettling, it is mainly because of the routinized, factory-like conditions under which Phase I trials are conducted. The effect is a little like that of Titicut Follies, Frederick Wiseman’s 1967 documentary about the Bridgewater State Hospital for the criminally insane. What stands out is not the casual cruelty (although it is occasionally evident) but the institutionalized indifference to the humanity of vulnerable people.
Fisher did fieldwork in six trial sites across the country. One was an academic site in a hospital, one was associated with a pharmaceutical company, four were commercial sites (two of which were independent and two affiliated with contract research organizations). The pharmaceutical company site was a state-of-the-art unit, but conditions at some of the commercial sites were grim. One was located in a former manufacturing facility, another in a converted warehouse. The largest was capable of housing three hundred subjects and included a vast space with over eighty beds lined up in rows. On Fisher’s first visit to the site, these beds were occupied by healthy subjects lying on their backs with their arms at their sides. “Many stared blindly at the ceiling,” she writes.
Several sites were located miles away from any hospital emergency room. Fisher compares them to “overcrowded prisons.” Yet many subjects had seen far worse. “We had dogs—bedbug sniffing dogs—come in because there were bedbugs in the facility,” one subject said. “Air conditioners were broken. The beds would stink . . . . It was horrible.” Some of us may imagine that research subjects take part in studies for humanitarian reasons. But in Phase I trial sites this is rare. “I wanted to make some money,” one subject told Fisher. “It’s definitely not because I want to save the world. Let’s get that on the
7Jon H. Harkness, Research Behind Bars: A History of Nontherapeutic Research on American Prisoners, Ph.D. dissertation, University of Wisconsin, 1996.