Research Letter TRIALS

Clinical Trials
Ó The Author(s) 2017
Commentary on Grady et al.: Using Reprints and permissions:
poor, uninsured minorities to test the DOI: 10.1177/1740774517722126

safety of experimental drugs

Carl Elliott

In 2004, a pharmaceutical researcher in Alabama was later demolished for fire and safety violations.
offered a paycheck to 21 clients of a Mobile homeless Prior to demolition, it was the largest trial site in North
center in exchange for testing an experimental smallpox America.6 In 2010, Roberto Abadie published The
vaccine.1 These people could expect little medical bene- Professional Guinea Pig, a deeply researched ethnogra-
fit from the study, of course. Smallpox was eradicated phy of semi-professional research subjects living on the
in 1980, and in the absence of a bioterrorist attack on margins in Philadelphia.7 In 2014, I wrote about the
Mobile, it was unlikely that clients of a homeless center recruitment of homeless people with schizophrenia to
there would need protection from it. But medical bene- test the safety of experimental antipsychotic drugs,
fit was not really the point. The main purpose of these including a mentally ill veteran named Walter Jorden
studies was to see if the experimental vaccine carried who died in a Phase I antipsychotic trial in New
unpleasant or dangerous side effects. Jersey.8 After decades of medical experimentation on
In some ways, studies like this are not unusual. the poor, the relevant question under debate is not
Pharmaceutical companies routinely pay desperately ‘‘Does it happen?’’ but rather ‘‘Are poor subjects being
poor subjects to test the safety of experimental prod- exploited?’’
ucts. In this case, however, 2 of the 21 subjects had to If the companion studies of Phase I trial subjects in
be hospitalized, one of them for acute myocarditis—an this issue of Clinical Trials do not directly address this
inflammation of the heart muscle that can cause sudden question, neither do they provide much reassurance.9,10
death. A third subject contracted pericarditis. It did not The subjects in these studies are largely poor, uninsured
help that the research team lost this subject’s medical and marginalized. Only 12.5% of the subjects surveyed
files for two years, one of many blunders that attracted at Pfizer’s trial site in New Haven had full-time employ-
federal scrutiny. When the Food and Drug ment. Although it is unclear just how many subjects
Administration (FDA) investigated in 2007, it found a had incomes lower than the federal poverty level (cur-
host of risky research practices ranging from careless rently set at US$12,060 for individuals), over 47% of
record-keeping to dubious recruiting procedures, as subjects had household incomes below US$25,000 a
well as little meaningful oversight by the Institutional year. In one of the studies, over 38% of the subjects
Review Board.2 The FDA eventually disqualified the had no health insurance, not even Medicaid. Equally
researcher in 2008, effectively barring him from doing disturbing is the fact that over half of the subjects test-
any more studies. But he continues to practice medicine ing the safety of new drugs for Pfizer in New Haven
in Alabama, marketing sexual enhancement procedures were Black.
as ‘‘Dr. Orgasm.’’3 Forty-five years after the end of the Tuskegee syphi-
By this point, nobody should really be shocked by lis study, those figures should give us pause. In 1979,
episodes like this. It has been over 20 years since Bob seven years after Peter Buxtun blew the whistle on the
Helms began publishing Guinea Pig Zero, the dark, Tuskegee study, the Belmont Report warned against
caustic job-zine that chronicled the world of poor peo- the recruitment of vulnerable groups such as ‘‘racial
ple who test the safety of experimental drugs for
money.4 In 1996, The Wall Street Journal reported that Center for Bioethics, Academic Health Center, University of Minnesota,
Eli Lilly was recruiting homeless alcoholics for safety Minneapolis, MN, USA
studies at its Indianapolis trial site.5 In 2005, Bloomberg
Corresponding author:
Markets found that a contract research organization Carl Elliott, Center for Bioethics, Academic Health Center, University of
called SFBC International was paying undocumented Minnesota, 410 Church Street SE, Minneapolis, MN 55455, USA.
immigrants to test new drugs in a converted motel that Email:
2 Clinical Trials 00(0)

minorities’’ and ‘‘the economically disadvantaged’’ for without invasive procedures, conducted by a familiar
medical research.11 The problem is not just that vulner- physician. Why substantially fewer subjects were will-
able groups are less capable of protecting themselves ing to enroll in first-in-human drug and vaccine trials
from potential harm—or, as the Belmont Report put it, and in studies of psychiatric drugs than in other studies
‘‘easy to manipulate as a result of their illness or socioe- was not explored. However, it is worth remembering
conomic condition.’’ It is not even that most research that such studies have produced several high-profile
sponsors in the United States, in stark contrast to the incidents in recent years, such as the suicide of Tracy
rest of the developed world, fail to guarantee that they Johnson during a Phase I duloxetine study at an Eli
will pay the medical bills of subjects who are injured in Lilly trial site in 2004,14 the life-threatening injuries of
their trials.12 The problem is also that it is unfair to ask six paid subjects in a TGN1412 trial at Northwick Park
a vulnerable group to bear the potential risks of in 2006,15 and last year’s Phase I study of BIA 10-2474
research if they are unlikely to benefit from the results. at a BioTrial facility in France, which left one subject
If there are many Americans less likely to have access dead and four others with possible brain damage.16
to the benefits of drug research than poor, uninsured If there is a surprise in these companion studies, it is
Black men in New Haven, it is hard to imagine who the conclusion that although subjects in Phase I trials
they might be. are largely poor and unemployed, their poverty and
The authors of the Belmont Report were especially unemployment ‘‘do not appear to affect either their
worried that researchers would be tempted to recruit motivations for participation or factors important to
subjects merely because of ‘‘their ready availability in their research enrollment decisions.’’ Exactly how the
settings where research is conducted.’’ At the time, that motivations of poor, unemployed research subjects to
sentence would have called to mind settings such as the enroll in research studies for money could be unaf-
Willowbrook State School, where researchers intention- fected by their poverty and unemployment goes largely
ally infected mentally disabled children with hepatitis unexplained. Grady and her colleagues suggest that the
A, or the Iowa State Penitentiary, where, in the early decision to sign up for a study may be like looking for
1970s, researchers fed prisoners a vitamin C-free diet a job, where subjects evaluate risks and decide if they
through gastrostomy tubes for three months to see if are worth the payment, possibly reassured ‘‘by knowing
they would get scurvy.13 (They did.) Now that research that adverse events are usually mild for healthy
sponsors conduct Phase I trials on the poor, there is no volunteers.’’
need to depend on institutional settings such as these. A more nuanced explanation has been offered by
Contract researchers can ensure ready access to willing medical sociologist Jill Fisher and her research team,
subjects by setting up in bleak urban neighborhoods who conducted semi-structured interviews with 178
next to the pawn shops, the plasma centers and the pay- subjects in Phase I studies at seven different United
day loan companies. States trial sites.17‘‘Some of our informants admit that
Twenty years ago, a spokesman for Eli Lilly they are hanging on ‘by the skin of their teeth’,’’
explained to the Wall Street Journal that the research Monahan and Fisher write, ‘‘staying in motels and liv-
subjects the company was recruiting from a homeless ing from day to day, just a step away from homeless-
shelter were driven by ‘‘altruism’’ and wanted ‘‘to help ness.’’17 Nearly 62% of their subjects were either Black
society.’’5 Even at the time, that explanation sounded or Hispanic, and 17% had household incomes of less
implausible. As Grady and her colleagues found, the than US$10,000 a year, well below the poverty level.
vast majority of subjects in Phase I trials sign up Almost 80% had taken part in more than one study,
because they need the money. Not only was money the with 26% participating in more than eleven. Some said
most common motivation; it was cited at a rate five they had enrolled in over 200 studies.
times that of the nearest competitor (57.6% vs 11.1%). While the choices of these subjects to enroll in stud-
When asked to compare money versus helping future ies may appear to be rational calculations, the way the
patients as a motivator, 72.3% cited money while only subjects speak about their decisions suggests something
24.7% cited the desire to help future patients. Over deeper and more emotionally driven. One obvious fac-
75% of subjects said they would be more willing to tor is financial desperation. ‘‘I guess the desperation far
endure invasive procedures if they were offered more outweighed the concerns,’’ said a Hispanic man on his
money. tenth study. ‘‘You know, when someone’s desperate,
Does that mean that money is more important to like they are not even gonna think twice, so I guess
their decision making than the risks of the studies? No, that’s where I was at.’’18 Some subjects directly com-
of course not. It should come as no surprise that poor pared their fear of risky studies to a far greater fear of
people—even desperately poor ones—are reluctant to poverty. ‘‘I was devastated, you know your money’s
enroll in studies they believe might injure them. Nor is cut in half; my rent was not [halved] or my gas bill,’’
it a surprise that subjects prefer low-risk studies said a White woman who had recently lost her job.
Elliott 3

‘‘And I frankly found that more terrifying than what- References
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