For-profit ethical review, coming to a clinical trial near you.

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medical examiner Health and medicine explained.

Ethics for Sale

For-profit ethical review, coming to a clinical trial near you.

By Carl Elliott and Trudo Lemmens

Carl Elliott is a professor at the Center for Bioethics at the University of

Minnesota and author of _Better Than Well: American Medicine Meets the

American Dream._ (http://www.tc.umn.edu/~ellio023/) Trudo Lemmens is a law

professor at the University of Toronto and the editor of the forthcoming book,

Law

and Ethics of Medical Research: Regulation, Conflict of Interest, and

Liability.

Posted Tuesday, Dec. 13, 2005, at 1:01 PM ET

If you missed the movie The Constant Gardener and need your fix of moral

outrage, you don't have to go to Africa to find it. Just look instead at the

_December cover story_

(http://www.bloomberg.com/apps/news?pid=specialreport & sid=aspHJ_sFen1s & refer=new\

s) in Bloomberg Markets about America's largest

clinical testing center. Managed by a company called SFBC International,

according

to Bloomberg, the 675-bed Miami testing center has been recruiting

undocumented Latino immigrants desperate for money, housing them in a converted

Holiday Inn, and paying them to take untested drugs in studies overseen by an

unlicensed medical director whose degree comes from an offshore medical school

in

the Caribbean.

So far, the plot is depressingly familiar. Drug companies spend $14 billion

a year testing new drugs. The products need to be tested for safety on

healthy people, and the healthy people most willing to ingest them are usually

those with plenty of time and little money. Nearly 10 years ago, the Wall

Street

Journal reported that Eli Lilly and Company was recruiting homeless

alcoholics to take part in drug trials in Indianapolis. In 2003, a previously

healthy

college student named _Traci committed suicide_

(http://www.slate.com/id/2126918/) in Lilly labs after being paid to take a new

version of an

antidepressant. Now Bloomberg is _reporting_

(http://www.bloomberg.com/apps/news?pid=specialreport & sid=aAC1o70dkzcI & refer=new\

s) that three years ago, Garry

Polsgrove, a homeless Vietnam veteran, checked into the Fabre Research Clinic,

a for-profit testing center in Houston. Polsgrove was in good health when he

entered the study and started taking clozapine, an antipsychotic drug, in

order to get some cash and a place to sleep. Twenty-two days later he was dead

of myocarditis.

The new wrinkle in the Bloomberg story is that many of the questionable

practices it reports unfolded under the nose of the for-profit organizations

that

researchers increasingly hire to conduct ethics reviews. In the United

States, the primary means of protecting research subjects are ethics committees

known as institutional review boards. IRBs originated in the 1970s in the wake

of various medical research scandals like the _Tuskegee Syphilis Study_

(http://www.cdc.gov/nchstp/od/tuskegee/time.htm) that left black men untreated

for syphilis between 1932 and 1972, and _a notorious study_

(http://www.hum.utah.edu/~bbenham/Research%20Ethics%20Website/INTMDcs_Willowbroo\

k.htm) at the

Willowbrook State School for the Retarded in New York, in which researchers

intentionally infected mentally disabled children with hepatitis A. The idea

was

that to protect the welfare of research subjects, all studies would be

reviewed in advance by an ethics committee independent of the researchers

conducting the study, whose scientific zeal might lead them to shortchange

safety.

Traditionally, IRBs have been volunteer committees made up of scientists and

clinicians working in the hospitals and medical schools where the studies they

review are being carried out.

_Continue Article _

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6?)

Today, however, the ethics review of more than half of all new drug

submissions to the Food and Drug Administration is handled by a single

for-profit

IRB, Western Institutional Review Board in Olympia, Wash. (according to

Western's owner, Bowen, as quoted in Bloomberg). At the SFBC clinic in

Miami,

some of the ethics review was done by a for-profit IRB owned by the wife of

an SFBC vice president. At the Fabre Research Clinic in Houston where Garry

Polsgrove died, the ethics review was conducted by a for-profit IRB run by

Louis Fabre, the clinic owner. (The Fabre clinic and its IRB have since shut

down.) If you find yourself down on your luck and are tempted to volunteer for

an industry-sponsored drug study, chances are that you will be entrusting your

safety to a private board that is operating with very limited government

oversight, and that is being paid by the drug company whose drugs you are

taking.

How did we get here? When IRBs were established a generation ago, medical

research was conducted mainly by individual investigators working in medical

schools who were funded by the federal government and who had little financial

stake in their studies. These days, medical research is a massive,

multinational corporate enterprise. Rather than contracting with academic

researchers

to test new drugs, the pharmaceutical industry has found it cheaper and more

efficient to conduct studies in physicians' offices, industry laboratories,

and private testing sites like SFBC's in Miami. As recently as 1994, 63 percent

of clinical trials were taking place in academic settings. Ten years later,

_that figure had shrunk to 26 percent_

(http://content.nejm.org/cgi/content/full/352/21/2160) . Along with

private-sector clinical research has come

private IRBs, which market themselves by promising fast and industry-friendly

service.

The demand for private IRBs isn't hard to understand. In today's research

environment, academic IRBs often are overmatched. They're often slow and

inefficient, and they are staffed by volunteers who would usually rather be

somewhere else. Nor are academic IRBs free from conflicts of interest. Their

members

are frequently asked to review studies being conducted by their friends and

colleagues. And a recent survey of academic IRB members found that _nearly

half had served as consultants to the drug industry_

(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=\

12915379 & dopt=Abstract)

..

But the private IRBs have a direct financial interest in keeping their

drug-company clients happy. If one for-profit IRB rejects a study as unethical,

the pharmaceutical company sponsoring the study can simply send it somewhere

else. Free-marketeers argue that there's a countervailing pressure that should

make drug companies welcome strict policing from the IRBs—the possibility

that a strict ethics review on the front end could head off a lawsuit on the

back end. But in reality, the incentives don't pan out that way. Lawsuits,

while

on the rise, are still relatively rare. For the companies bankrolling the

clinical trials, litigation is a quite-manageable cost of doing business.

Surprisingly, for-profit IRBs have drawn little criticism from bioethicists.

Instead, some university and government scientists are increasing their

influence. A few universities, such as s Hopkins, have begun _using

for-profit IRBs to review their research_

(http://irb.jhmi.edu/Guidelines/wirb.html) .

Ezekiel Emanuel, the chief of bioethics at the National Institutes of

Health, spoke enthusiastically about for-profit IRBs in general and Western IRB

in

particular during a _presentation about research review that he made to the

President's Council on Bioethics_

(http://www.bioethics.gov/transcripts/sep02/session2.html) a few years ago. " I

think there are a lot of reasons that make

Western and a few of the others very good, " Emanuel said. " One is certainly

leadership and dedication to doing the right thing, and believing that by

doing the right thing, you'll be successful, and in their case profitable. " Yet

according to Bloomberg's December cover story, Western IRB gave ethical

approval to studies in Los Angeles and Georgia that later turned out to be

fraudulent. The researchers involved reportedly wound up in prison for lying to

the

FDA and putting the lives of subjects in danger. Western IRB _has also been

sued_ (http://www.sskrplaw.com/gene/hamletcomplaint.pdf) for approving a

placebo-controlled study of a Genentech drug called Raptiva. In that study,

Bill

Hamlet, a patient in North Carolina ill with psoriatic arthritis, claims

that he was taken off his regular medications, which had been effective, and

given a placebo instead. When Hamlet withdrew from the study six months later,

he says his body was covered with bleeding scabs and he was bedridden from his

psoriatic arthritis. The lawsuit was settled out of court.

IRBs were never intended to be formal regulatory bodies. They were supposed

to provide a kind of professional self-regulation, in which scientists were

advised by their colleagues. " I will begin by noting that IRBs are not

policing bodies, watchdogs, or auditing agents, " Levine of Yale

University,

the former editor of the journal IRB, said when he testified before Congress

in 1998. " IRBs were established to work collaboratively with investigators. "

That mission might have made sense 30 years ago. Today, however, the

prevalence of private-sector drug research and the push to commercialize every

facet

of medical research makes the original model hopelessly outdated. Research

subjects need a watchdog to protect them, and not one that is owned by the

pharmaceutical industry. If IRBs cannot do the job, then we need to replace

them

with something that can.