The Mild Torture Economy

Carl Elliott
Medical Research for Hire:
The Political Economy of Pharmaceutical Clinical Trials
by Jill Fisher.
Rutgers, 257 pp., £23.50, January 2009, 978 0 8135 4410 6

When Experiments Travel:

Clinical Trials and the Global Search for Human Subjects
by Adriana Petryna.
Princeton, 258 pp., £18.95, June 2009, 978 0 691 12657 9

The Professional Guinea Pig:

Big Pharma and the Risky World of Human Subjects
by Roberto Abadie.
Duke, 184 pp., £15.99, October, 978 0 8223 4823 8

T
he last few years haven’t been the
best for the business of medical re-
search. There was the Sanofi-Aventis
researcher in California who was arrested
waving a loaded handgun; police found a
package of cocaine stuffed in his under-
wear. There was the psychiatric researcher
in Oklahoma City whose medical licence was
suspended after he infected two patients
with genital herpes, and who was invest-
igated by the FDA after he barred a re-
search subject from leaving his clinical trial
facility. In Miami, investigative reporters
for Bloomberg Markets magazine discovered
that a contract research organisation called
SFBC International was testing drugs on
undocumented immigrants in a rundown
motel; since that report, the motel has been
demolished for fire and safety violations.
Several pharmaceutical companies have been
caught up in controversial cases of suicide,
such as that of Dan Markingson, a young
man who stabbed himself to death while
taking Seroquel in an AstraZeneca trial at
the University of Minnesota, and Traci John-
son, who hanged herself in a study of Cym-
balta at the Eli Lilly trial site in Indianapolis.
Britain had its own disaster at Northwick
Park Hospital in north-west London, where
six healthy subjects nearly died in a ‘first in
man’ study of a monoclonal antibody. And
Pfizer has spent longer than a decade deal-
ing with the fallout of a study in Kano,
Nigeria, in which 11 children died during a

1 9 september 2010
meningitis trial allegedly rigged to show
that the antibiotic Trovan was superior to a
competitor’s drug. The Trovan case has
wound its way through various courts for
years, generating millions of dollars in
damages and a stubborn public relations
problem for Pfizer.
It is time for a ‘rebranding’ campaign,
according to the Center for Information and
Study on Clinical Research Participation.
CISCRP is a non-profit group funded by
pharmaceutical companies, academic health
centres and contract research organisations.
According to CISCRP, the public image of
the pharmaceutical industry ranks along-
side that of used-car dealerships and tob-
acco companies, and too often the media
portray pharmaceutical research as ‘decept-
ive and evil’. So CISCRP has launched a new
public relations initiative, called ‘Medical
heroes can be found in everyday places.’
Funded by the pharmaceutical company Eli
Lilly and orchestrated by Ogilvy Health-
world, the purpose of the initiative is to
transform the image of the clinical trial vol-
unteer from ‘guinea pig’ to ‘medical hero’.
CISCRP has produced a slick public service
announcement; it is sponsoring ‘clinical re-
search education days’ all over America; and
it is distributing posters, DVDs and shiny
‘Medical Hero’ badges to research subjects.
Apparently the strategy is working: subject
recruitment is up in areas where the cam-
paign has run. Even bioethicists are pitch-
ing in. A team from the Department of Clin-
ical Bioethics at the National Institutes of
Health recently argued in the Journal of the
American Medical Association that signing up
for clinical trials is a prima facie moral duty
2 9 september 2010
owed by every citizen.
Over the past twenty years or so, without
much fanfare, clinical research has under-
gone a remarkable free-market conversion.
Until the early 1990s, most pharmaceutical
research on human subjects was conducted
by physicians in universities and teaching
hospitals. (The FDA, which must approve
drugs before they can be marketed, doesn’t
conduct clinical trials itself.) However,
pharmaceutical companies have been in
search of cheaper, more efficient venues
and today about 70 per cent of clinical trials
take place in the private sector, often in
the offices of private physicians or at de-
dicated sites. Clinical research has become
a multibillion-dollar global industry, spawn-
ing spin-off businesses that barely exist-
ed 25 years ago, from patient recruitment
firms and medical communication agencies
to for-profit research ethics boards. The
most important new players are contract
research organisations (CROs) such as Par-
exel, Quintiles, PPD and Covance, which
have built themselves into corporate giants
by taking up the management of clinical
trials. The research that many of us used
to imagine as a humanitarian enterprise,
carried out by selfless scientists and fund-
ed by Pink Ribbon campaigns and ‘Race
for the Cure’ marathons, is actually a thor-
oughly Taylorised corporate system, out-
sourced and streamlined for maximum
efficiency.
It is striking just how little is known
about the new clinical trials industry. Partly
this is because it is so widely dispersed.
Back in the old days, if you worked in a
medical school or teaching hospital, you
could often get a feel for a clinical trial sim-
ply by walking down the hall. Now you
might need to go to India or Uzbekistan.
Even if you restricted yourself to domestic
studies, you would log a lot of miles trying
to visit all the various stations in the pro-
duction line. The trial itself might take
place at fifty different sites, ranging from
Ivy League teaching hospitals to a business
park near Toronto airport. The ethics com-
mittee approval would probably come from
Olympia, Washington; the subject recruit-
ment could be managed in Dallas, Texas;
and the trial results might be written up in
Princeton, New Jersey. It is no wonder only
industry insiders seem to know exactly
what is going on. When Bloomberg reporters
discovered that SFBC International was
paying immigrants to be test subjects in a
dilapidated former Holiday Inn in Miami,
SFBC had recently been named one of the
best small businesses in America by Forbes
magazine. The Holiday Inn testing facility
was the largest in North America, and had
been operating for nearly ten years before
inspectors noticed there was anything
wrong.
Lodged somewhere between the secrecy
and the scandals is the work of a new gen-
eration of ethnographers who are quietly
studying the way the clinical trials business
operates. What interests Jill Fisher, Adriana
Petryna and Roberto Abadie is not so much
the occasional outrage uncovered by in-
vestigative reporters, or even the formal
regulation of clinical trials. They are more
concerned with the everyday pressures and
moral choices facing the workers who man
the production line: the private-sector phys-
3 9 september 2010
icians who conduct the trials, the study
monitors and trial co-ordinators who over-
see them, and the research subjects who
take experimental drugs, often in exchange
for free medical care or a wage. What does
clinical research look like when everyone is
in it for the money?
For a start, it looks a lot less like science.
‘I do not do original research; I do con-
tract research,’ says a private physician-
researcher in Medical Research for Hire. A con-
tract researcher does not come up with
original ideas, or design research proto-
cols, or analyse research results, or write
them up for scientific publications. All of
this is done by the pharmaceutical company
or its hired specialists. What a contract re-
searcher does is recruit subjects, monitor
their clinical care and sign off on the paper-
work. Not a lot of original work is done,
and in some cases, not much work at all
(a running joke has it that physicians do
clinical trials in order to improve their golf
games). The industry term for these near-
absent physicians is ‘phantom investig-
ators’. Usually they will ‘come in on a daily
basis, on most days, and they’ll sign off on
all the things they need to sign off on, see
any patients they need to see, and they’re
gone,’ a study monitor says to Fisher. The
researchers are usually on-site for no more
than an hour or two a day.
Contract researchers may not do much
intellectual work, but this doesn’t mean
they are not well paid. A part-time contract
researcher conducting four or five clinical
trials a year can earn an average of $300,000
in extra income. In 2000, a full-time clinical
trial site earned an average of $1.6 million.
According to Fisher, any given service will
generate between two and five times as
much money for a physician when a pharm-
aceutical company is paying the bill as when
a health insurance company or a govern-
ment agency is paying. Even an ordinary
office visit will be paid at twice the usual
rate if the visit is part of a research study.
Some physicians sign up as contract re-
searchers for the same reasons they might
peddle nutraceuticals or dispense cosmetic
Botox injections. It is a way to make extra
money.
H
owever, the most valuable com-
modity in the contract research
business is not the physician. It is
the patient: ideally, the sort of patient that
the industry calls ‘ready to recruit’. Ready to
recruit patients are sick people who can
easily be persuaded to enrol in clinical trials,
often because they are so poor that they
have no better alternative. If a patient can
be persuaded to enrol in a study quickly,
so much the better: drug patents last only
twenty years, and the patent clock ticks
down while the drug is being tested. Four
out of every five clinical trials are forced to
extend their timelines because of recruiting
delays.
For years the demand for research sub-
jects has been growing, driven not least by
the sheer number of clinical trials being
conducted in the desperate search for new
blockbuster drugs. Nobody really knows
how many trials the industry is currently
conducting, but a WHO official estimates
that 20,000 are initiated each year. They are
getting larger and more complex, partly to
4 9 september 2010
satisfy safety regulations, but also because
many of the drugs being tested are so simil-
ar to drugs already on the market: if a new
drug is only incrementally better than a
control drug or placebo, demonstrating a
statistical difference requires many more
research subjects. The pool of potential
subjects is gradually becoming depleted, in
part because so many subjects in North
America and Western Europe are taking
other medications, which will often exclude
them from enrolling in trials. Drug com-
panies need ‘treatment-naive’ subjects, who,
like the ‘ready to recruit’, are easier to find
in the developing world. In 1991, only 10 per
cent of clinical trials were conducted in
emerging markets; by 2005, that figure had
increased to 40 per cent.
According to Adriana Petryna’s When Ex-
periments Travel, the most popular place for
new trial sites is Central and Eastern Eur-
ope; there are plenty of sites, too, in the
Asia-Pacific region. Between 1995 and
2006, the highest annual increases in the
number of active clinical researchers oc-
curred in Russia, Argentina, India, Poland,
China and Brazil. Many of these places
have established a foothold in the industry
as ‘rescue countries’: drug companies go
there when they need data quickly – when
their trials in the West have failed to show
the drug is effective, for example, or when
they have been unable to recruit enough
subjects. Poland has been a popular place to
test urology drugs and asthma drugs, a
Czech physician tells Petryna; the Czech
Republic has been a good spot for anti-
biotics and arthritis drugs. ‘There were
treatment-naive, steroid-naive, statin-naive
people – people you could hardly find in the
US or Western Europe,’ the physician ex-
plains. ‘We had extremely high recruitment
rates.’
The move into Eastern Europe began with
the ‘opportunity’ phase, or the gold rush,
when the trials industry first discovered the
rescue countries. In the early post-Soviet
years, clinical trials were easy to launch.
‘No one cared about the content of the
investigations,’ the Czech physician says.
‘Ethical approval was a mere formality.’
There followed a ‘normalisation’ phase,
when the trials became a routine, accepted
part of healthcare. Over time, patients no
longer saw them as experimental, but as
part of their standard medical treatment.
Finally came the ‘exhaustion’ phase. Too
many companies were competing for sub-
jects; the subjects began to get choosy;
regulations began to tighten. So the clinical
trials industry began to move further east –
to Russia, for example, Ukraine, Uzbek-
istan and Kazakhstan.
The move to poorer countries intensifies
the ethical problem created by a market-
based trial system. The patients have even
less access to standard medical care than
patients in the US, and by enrolling in
trials they can get drugs that they could
not otherwise afford – never mind that the
drugs are experimental, or may be placebos.
Physicians who are paid handsomely to re-
cruit their patients for trials will often find
the money hard to resist, since they make
so little practising ordinary medicine. ‘In
Russia, a doctor makes $200 a month,’ a
contract research executive tells Petryna,
‘and he is going to make $5000 per Alz-
5 9 september 2010
heimer’s patient.’
Contract researchers may find that their
sponsors do not welcome bad news about
the trials, especially if the drug appears un-
safe. Reporting that subjects have exper-
ienced a ‘serious adverse event’ (industry-
speak for the worst side effects) may mean
losing the contract. One physician told
Petryna she had done a clinical trial on a
drug that appeared dangerous, but when
she documented her concerns and recom-
mended redesigning the trial, the sponsor
ignored her and successfully submitted the
drug for approval. The drug was later with-
drawn from the market. ‘We never got a
contract from that manufacturer again,’
she adds.
Financial incentives present a different
ethical problem for a Phase I trial, the pur-
pose of which is to determine if a drug is
safe. Most Phase I trials are done on healthy
subjects. Until the mid-1970s, this usually
meant prisoners; today the trials are done
mainly on the poor, who sign up for the
money. Not just any poor person will do,
though. Ideally they should be between the
ages of 18 and 45 and in good health, or at
least good enough to pass the screening
tests, and they should not be taking any
drugs other than the ones they are testing.
Most important, they need to be available to
check into a testing facility for up to several
weeks at a time, where they will eat, sleep
and endure a daily routine of blood draws,
urine tests and invasive medical proced-
ures. It isn’t hard to imagine the sort of
people that make up the bulk of Phase I tri-
al subjects: the unemployed, immigrants,
contract workers, university students, ex-
cons and anyone else with a reason for
working off the grid. Some people even
manage to make a living as professional
guinea pigs, travelling from one trial site to
another for years. One guinea pig pro de-
scribes it to Roberto Abadie as the ‘mild
torture economy’.
The issue of payment has always worried
regulators and ethicists, who are concerned
that excessive fees will tempt impoverished
subjects to take risks with their health.
Nevertheless, the amount of money offered
to subjects has, over the years, gradually
crept up. At the low end of the pay scale are
‘bioequivalence trials’, or what guinea pig
pros call ‘bleed and feeds’. These studies
compare standard FDA-approved drugs at
the end of a patent cycle with their gen-
eric equivalents; they pay the least because
they are seen as the least risky. The most
lucrative studies are longer trials testing the
safety of new drugs, with lots of in-patient
time and plenty of unpleasant medical pro-
cedures. These sometimes pay subjects up-
wards of $6000. (One recent study spons-
ored by Nasa offered subjects $17,000 to lie
in bed for 60 days, not to test a drug, but to
study the effects of microgravity on the hu-
man body.) The range of subjects eligible
for payment has also expanded consider-
ably. Several years ago, most trial sites paid
only healthy adult subjects. Now some sites
pay parents to enrol their children. Many
also pay subjects who are sick, especially
subjects with milder chronic illnesses such
as asthma, or whose metabolism is im-
paired by kidney or liver disease. A study
currently being advertised in St Paul, Min-
nesota, near where I live, is testing a drug
6 9 september 2010
on patients whose kidney function is so
badly compromised they are on dialysis.
The sponsors will pay patients $2525 to
take part, as long as they are willing to
spend four nights at the test site and come
back for eight out-patient visits.
P
erhaps the most fertile guinea pig-
ging territory in the United States is
the region around Philadelphia, which
is home to a number of medical schools,
pharmaceutical companies and clinical trial
sites. For his work on The Professional Guinea
Pig, Abadie lived in an anarchist community
in West Philadelphia, many of whose mem-
bers enrol in trials to fund their work as
artists and activists. These trial subjects
have few illusions about the value of
what they are doing or why they are doing
it. ‘They pay you just to demean you to
animal status,’ one seasoned trial subject
says. A Latino man with the pseudonym
KingLabRat says he began enrolling in
studies in the mid-1980s after he was dis-
charged from the army, allegedly for beat-
ing up his sergeant. In between trials he
sells drugs and works in a morgue. ‘It’s for
the rent-use of your body and the inside op-
erating fluids,’ he explains. ‘That’s it pretty
much in a nutshell.’ KingLabRat has been
injected so many times he has scars up and
down his arms, which he regards as badges
of honour.
Guinea pigging may have become a job,
but it does not carry many benefits. Re-
search subjects do not have the right to
workers’ compensation, health insurance
or a minimum wage. Trial sites are not reg-
ulated in the same way as workplaces. If
subjects are harmed by the drugs they take,
they have no right to compensation, and
they may well have to pay their own medical
expenses. According to a survey published
in the New England Journal of Medicine, only 16
per cent of the policies issued by academic
health centres in the US offer free care to re-
search subjects injured in trials. Litigation,
the usual American substitute for regulat-
ion, is not really an option for most guinea
pigs, at least not if they want to continue
doing trials; just a whiff of defiance can
be enough to get a subject banned from a
research site. Robert Helms, a veteran of
more than 80 trials who founded a jobzine
for research subjects in the mid-1990s
called Guinea Pig Zero, compares guinea pig-
ging to prostitution. ‘They are penetrating
your body,’ Helms says. ‘You are renting out
your body and they don’t care about what
you are thinking.’
Many of the guinea pigs in West Phila-
delphia are anti-corporate political activists
who take the easy money on offer instead of
signing up for a nine to five job. Yet because
they don’t buy into the ‘medical heroes’
propaganda of the clinical trials industry,
they have no incentive to take the job ser-
iously. ‘I even try to sabotage the results now
and then,’ one subject tells Abadie. ‘I am
pretty cynical and don’t think that the trials
result in much medical benefit.’ These
activists take up guinea pigging because it
allows them a measure of distance from
ordinary corporate capitalism, yet it is only
by virtue of their participation that the
system can work.
None of these ethnographers appear to
place much confidence in the system’s cur-
7 9 september 2010
rent means of protecting human subjects.
There is a heavy reliance on the informed-
consent forms that subjects are expected
to sign, but as Fisher points out, most
subjects have already made up their minds
to enrol in a trial before they even see
the form. Institutional review boards, the
quasi-regulatory bodies charged with over-
seeing the ethics of clinical trials, are often
for-profit companies paid by the sponsors
of the research they are evaluating. If one
review board says a study is unethical, the
sponsor can simply take it to another one.
No wonder some subjects feel as if they are
on their own. As Helms puts it: ‘The auth-
orities, the regulators, the courts, they are
not there to protect you if you are working-
class or a guinea pig, anybody at the low
end of the totem pole.’
By turning clinical research over to the
market we have created a system in which
private physician-investigators can make far
more money persuading their patients to
enrol in research studies than by simply
treating their illnesses; in which patients
sign up to test new drugs, either because they
need the money or because they have no
way to pay for ordinary healthcare; in which
investigators are financially punished for
telling companies that their drugs are risky
or dangerous; and in which even ethical
oversight has become a revenue-generating
mechanism. Lost in this business model
are the human research subjects themselves.
As a CRO manager in Eastern Europe tells
Petryna, apparently without irony: ‘We don’t
see patients, we see data.’ c