CLINICAL
Research Letter
Commentary on Grady et al.: Using
poor, uninsured minorities to test the
safety of experimental drugs
Carl Elliott
In 2004, a pharmaceutical researcher in Alabama
offered a paycheck to 21 clients of a Mobile homeless
center in exchange for testing an experimental smallpox
vaccine.1 These people could expect little medical bene-
fit from the study, of course. Smallpox was eradicated
in 1980, and in the absence of a bioterrorist attack on
Mobile, it was unlikely that clients of a homeless center
there would need protection from it. But medical bene-
fit was not really the point. The main purpose of these
studies was to see if the experimental vaccine carried
unpleasant or dangerous side effects.
In some ways, studies like this are not unusual.
Pharmaceutical companies routinely pay desperately
poor subjects to test the safety of experimental prod-
ucts. In this case, however, 2 of the 21 subjects had to
be hospitalized, one of them for acute myocarditisan
inflammation of the heart muscle that can cause sudden
death. A third subject contracted pericarditis. It did not
help that the research team lost this subjects medical
files for two years, one of many blunders that attracted
federal scrutiny. When the Food and Drug
Administration (FDA) investigated in 2007, it found a
host of risky research practices ranging from careless
record-keeping to dubious recruiting procedures, as
well as little meaningful oversight by the Institutional
Review Board.2 The FDA eventually disqualified the
researcher in 2008, effectively barring him from doing
any more studies. But he continues to practice medicine
in Alabama, marketing sexual enhancement procedures
as Dr. Orgasm.3
By this point, nobody should really be shocked by
episodes like this. It has been over 20 years since Bob
Helms began publishing Guinea Pig Zero, the dark,
caustic job-zine that chronicled the world of poor peo-
ple who test the safety of experimental drugs for
money.4 In 1996, The Wall Street Journal reported that
Eli Lilly was recruiting homeless alcoholics for safety
studies at its Indianapolis trial site.5 In 2005, Bloomberg
Markets found that a contract research organization
called SFBC International was paying undocumented
immigrants to test new drugs in a converted motel that
TRIALS
Clinical Trials
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was later demolished for fire and safety violations.
Prior to demolition, it was the largest trial site in North
America.6 In 2010, Roberto Abadie published The
Professional Guinea Pig, a deeply researched ethnogra-
phy of semi-professional research subjects living on the
margins in Philadelphia.7 In 2014, I wrote about the
recruitment of homeless people with schizophrenia to
test the safety of experimental antipsychotic drugs,
including a mentally ill veteran named Walter Jorden
who died in a Phase I antipsychotic trial in New
Jersey.8 After decades of medical experimentation on
the poor, the relevant question under debate is not
Does it happen? but rather Are poor subjects being
exploited?
If the companion studies of Phase I trial subjects in
this issue of Clinical Trials do not directly address this
question, neither do they provide much reassurance.9,10
The subjects in these studies are largely poor, uninsured
and marginalized. Only 12.5% of the subjects surveyed
at Pfizers trial site in New Haven had full-time employ-
ment. Although it is unclear just how many subjects
had incomes lower than the federal poverty level (cur-
rently set at US$12,060 for individuals), over 47% of
subjects had household incomes below US$25,000 a
year. In one of the studies, over 38% of the subjects
had no health insurance, not even Medicaid. Equally
disturbing is the fact that over half of the subjects test-
ing the safety of new drugs for Pfizer in New Haven
were Black.
Forty-five years after the end of the Tuskegee syphi-
lis study, those figures should give us pause. In 1979,
seven years after Peter Buxtun blew the whistle on the
Tuskegee study, the Belmont Report warned against
the recruitment of vulnerable groups such as racial
Center for Bioethics, Academic Health Center, University of Minnesota,
Minneapolis, MN, USA
Corresponding author:
Carl Elliott, Center for Bioethics, Academic Health Center, University of
Minnesota, 410 Church Street SE, Minneapolis, MN 55455, USA.
Email: ellio023@tc.umn.edu
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-
able groups are less capable of protecting themselves
from potential harmor, as the Belmont Report put it,
easy to manipulate as a result of their illness or socioe-
conomic condition. It is not even that most research
sponsors in the United States, in stark contrast to the
rest of the developed world, fail to guarantee that they
will pay the medical bills of subjects who are injured in
their trials.12 The problem is also that it is unfair to ask
a vulnerable group to bear the potential risks of
research if they are unlikely to benefit from the results.
If there are many Americans less likely to have access
to the benefits of drug research than poor, uninsured
Black men in New Haven, it is hard to imagine who
they might be.
The authors of the Belmont Report were especially
worried that researchers would be tempted to recruit
subjects merely because of their ready availability in
settings where research is conducted. At the time, that
sentence would have called to mind settings such as the
Willowbrook State School, where researchers intention-
ally infected mentally disabled children with hepatitis
A, or the Iowa State Penitentiary, where, in the early
1970s, researchers fed prisoners a vitamin C-free diet
through gastrostomy tubes for three months to see if
they would get scurvy.13 (They did.) Now that research
sponsors conduct Phase I trials on the poor, there is no
need to depend on institutional settings such as these.
Contract researchers can ensure ready access to willing
subjects by setting up in bleak urban neighborhoods
next to the pawn shops, the plasma centers and the pay-
day loan companies.
Twenty years ago, a spokesman for Eli Lilly
explained to the Wall Street Journal that the research
subjects the company was recruiting from a 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
implausible. As Grady and her colleagues found, the
vast majority of subjects in Phase I trials sign up
because they need the money. Not only was money the
most common motivation; it was cited at a rate five
times that of the nearest competitor (57.6% vs 11.1%).
When asked to compare money versus helping future
patients as a motivator, 72.3% cited money while only
24.7% cited the desire to help future patients. Over
75% of subjects said they would be more willing to
endure invasive procedures if they were offered more
money.
Does that mean that money is more important to
their decision making than the risks of the studies? No,
of course not. It should come as no surprise that poor
peopleeven desperately poor onesare reluctant to
enroll in studies they believe might injure them. Nor is
it a surprise that subjects prefer low-risk studies
physician. Why substantially fewer subjects were will-
ing to enroll in first-in-human drug and vaccine trials
and in studies of psychiatric drugs than in other studies
was not explored. However, it is worth remembering
that such studies have produced several high-profile
incidents in recent years, such as the suicide of Tracy
Johnson during a Phase I duloxetine study at an Eli
Lilly trial site in 2004,14 the life-threatening injuries of
six paid subjects in a TGN1412 trial at Northwick Park
in 2006,15 and last years Phase I study of BIA 10-2474
at a BioTrial facility in France, which left one subject
dead and four others with possible brain damage.16
If there is a surprise in these companion studies, it is
the conclusion that although subjects in Phase I trials
are largely poor and unemployed, their poverty and
unemployment do not appear to affect either their
motivations for participation or factors important to
their research enrollment decisions. Exactly how the
motivations of poor, unemployed research subjects to
enroll in research studies for money could be unaf-
fected by their poverty and unemployment goes largely
unexplained. Grady and her colleagues suggest that the
decision to sign up for a study may be like looking for
a job, where subjects evaluate risks and decide if they
are worth the payment, possibly reassured by knowing
that adverse events are usually mild for healthy
volunteers.
A more nuanced explanation has been offered by
medical sociologist Jill Fisher and her research team,
who conducted semi-structured interviews with 178
subjects in Phase I studies at seven different United
States trial sites.17Some of our informants admit that
they are hanging on by the skin of their teeth,
Monahan and Fisher write, staying in motels and liv-
ing from day to day, just a step away from homeless-
or Hispanic, and 17% had household incomes of less
than US$10,000 a year, well below the poverty level.
Almost 80% had taken part in more than one study,
with 26% participating in more than eleven. Some said
they had enrolled in over 200 studies.
While the choices of these subjects to enroll in stud-
ies may appear to be rational calculations, the way the
subjects speak about their decisions suggests something
deeper and more emotionally driven. One obvious fac-
tor is financial desperation. I guess the desperation far
outweighed the concerns, said a Hispanic man on his
tenth study. You know, when someones desperate,
like they are not even gonna think twice, so I guess
thats where I was at.18 Some subjects directly com-
pared their fear of risky studies to a far greater fear of
poverty. I was devastated, you know your moneys
cut in half; my rent was not [halved] or my gas bill,
said a White woman who had recently lost her job.
Elliott
And I frankly found that more terrifying than what-
ever I was going to do during the trial.
For many subjects, the decision to enroll was shaped
by their experiences with prison and the police. One
subject said, (T)heres a little risk, but its well worth
it. Like its not as risky as going to sell some drugs or
robbing a bank, you know. Some explained that the
risks of an experimental drug were minimal compared
to the risks of their everyday lives, where arrest was a
constant threat. Ive been in different situations, so
this little drug, thats not gonna scare me more than
whats going on out where in them places Ive lived at,
another subject said.
In contrast to Grady and her colleagues, who believe
that their findings should alleviate some concerns about
distorted judgment among healthy volunteers, Fisher
worries that many of the subjects she interviewed have
become desensitized to the potential risks of studies.19
Partly this is because of the casual, routinized fashion in
which staff members present those risks, but it is also
because of the particular way that trials are typically con-
ducted. Most Phase I trial sites are standard feed em
and bleed em facilities, with relatively unsophisticated
medical capabilities; most of the studies conducted at
those sites are homogeneous, with little variation between
protocols; and most are set up for maximum efficiency,
like a factory assembly line, with minute-by-minute sche-
duling and barcodes for the subjects. Even the language
used by staff members transforms harms into data
points; staff call the injuries produced AEs, so that
even the word adverse event often goes unmentioned.
The result is what Fisher calls the banalization of risk.
Many subjects she interviewed appeared far less worried
about the risk of being harmed by an experimental drug
than the risk of failing to qualify for the next study.
If current practice is any indication, most research
sponsors are comfortable with using Americas vast
supply of poor, uninsured minorities to test the safety
of experimental drugs. Morally justifying such a prac-
tice requires one to imagine the decisions of subjects as
fully autonomous and free, rather than the product of
financial desperation. It also requires imagining that
the bargain being offered to subjects is fairnot just
that the payment is reasonable, but that the research
oversight system will protect them from harm, that the
conditions of the study are not degrading, and that if
subjects are injured, their medical bills will be paid and
they will be compensated for their pain, suffering and
the inability to work. No doubt there are some United
States Phase I trial sites where most of this is true. But
I am afraid there are many more where it is not.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
3
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