The Mild Torture Economy, London Review of Books

8/8/2019 The Mild Torture Economy, London Review of Books

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The last few years havent 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 apackage 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 youngman 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

The Mild Torture EconomyCarl ElliottMedical 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


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meningitis trial allegedly rigged to show

that the antibiotic Trovan was superior to a

competitors 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 serviceannouncement; 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

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, doesnt

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 usedto 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


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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 onlyindustry 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 byForbes

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-

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 ofthis 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 theyll sign off onall the things they need to sign off on, see

any patients they need to see, and theyre

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 doesnt 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.


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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.

However, 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. Fourout 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

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 percent of clinical trials were conducted in

emerging markets; by 2005, that figure had

increased to 40 per cent.

According to Adriana PetrynasWhen 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 placeshave 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


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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 nolonger 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 evenless 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-

heimers 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 acontract 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 atleast 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 isnt 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-


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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 pigpros 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 tostudy 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

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.

Perhaps 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 onThe 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. Its forthe rent-use of your body and the inside op-

erating fluids, he explains. Thats 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


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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 jobzinefor 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 dont 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 dont 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 dont 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 systems cur-

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 noway 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 dont

see patients, we see data. c

Documents

The Mild Torture Economy, London Review of Books