Research lab accused of racism in clinical trials
George E. Jordan
KENILWORTH, N.J. — Cecil Pickett is a scientist at the top
of his game.
As the head of research at Schering-Plough, he lives in a world
of enzymes, viruses and proteins — the building blocks of
life and disease.
So, by his own admission, he was taken aback last month when an
advocacy group accused his laboratory of racism.
Schering-Plough is on the verge of a breakthrough in the treatment
of hepatitis C — a virus that infects 4 million in the United
States and 200 million worldwide. But hepatitis patient advocates
allege the Kenilworth company excluded blacks from early human testing
to skew the data and accelerate regulatory approval. It was the
first time a drugmaker was accused of racial bias for the design
of a clinical trial.
It’s always tough to separate politics from the drug industry,
but this time it was personal. Pickett, who grew up as one of nine
children in a rural Illinois town, is black in an industry where
few African Americans reach the top.
“That’s absurd,” said Pickett of the allegations,
as he stood behind his desk recently, hands fanned outward for emphasis.
“It makes no sense at all.”
The dispute highlights a collision of scientific research and social
realities in the development of life-saving medicines. It also illustrates
conflicting principles of risk vs. benefit in the ethical guidelines
that have governed all human experimentation since the Nazi era
Nuremberg Trials and the notorious Tuskegee Syphilis Study.
In the Schering-Plough case, the issue is not whether to experiment
on people — but who to include.
African Americans don’t respond well to existing hepatitis
therapies, Pickett said. They were kept out of the early trial in
case the drug wasn’t safe, he said. There were always plans
to include blacks in the final Phase III trials, he said.
“The point is we didn’t want to expose a population
we know are poor responders to existing therapies to an investigational
new drug,” he said.
Bioethicists warn the dust-up is certain to play out again as pharmaceutical
companies that employ tens of thousands in people in New Jersey
deliver drugs that target diseases suffered by racial and ethnic
“It’s going to put the FDA, drug companies, ethicists
and everybody in an interesting boat sailing in the genetic sea,”
said Arthur Caplan, chairman of the department of medical ethics
at the University of Pennsylvania and director of its Center for
What if, for example, pharmaceutical researchers discovered a promising
cure for HIV2, the strain of the AIDS virus in Sub-Saharan Africa?
Despite a legitimate scientific rationale, Caplan said the scientists
“could look like the world’s greatest racist”
for limiting human testing to poor African villagers.
Schering-Plough faces a similar problem now, he said.
“Somebody better wake up in Washington to come up with the
next generation of rules that tells how to go forward with testing
drugs,” he said.
A spokesman for the FDA did not return telephone messages seeking
A Big Market
Hepatitis, an inflammation of the liver, infects about two of every
five HIV sufferers in the United States, mainly because both viruses
are transmitted by contact with blood. It is a leading cause of
chronic liver disease. Infection typically happens during sex, childbirth
or the sharing hypodermic needles by drug addicts.
About half of people infected with the most common strain of hepatitis
C in the United States do not respond well to the existing treatment,
a combination of the protein interferon and anti-viral agent ribavirin.
The injections are so physically demanding that often patients qualify
for temporary disability.
For reasons unknown to science, blacks have even a lower response
rate to interferon-based drugs, if they work at all.
That’s why Schering-Plough’s hepatitis drug, designed
specifically to treat “non-responders,” is being watched
so closely by both the pharmaceutical industry and HIV/AIDS activists.
It also has the eye of Wall Street as a potentially important source
of revenue for the company. The worldwide market for hepatitis C
drugs is expected to reach nearly $4 billion next year.
Schering-Plough’s drug is a protease inhibitor, a genetically
engineered agent designed to switch off the hepatitis virus’s
ability to copy itself and spread. Stop its ability to spread, the
thinking goes, and halt the disease.
Code-named SCH 503034, the tablet has been granted fast track status
by the FDA, which means the agency is closely monitoring Schering-Plough’s
testing program. Phase III trials that involve thousands of patients
could get under way next year.
Clinical trials occur in four phases that play out over several
years. Generally, Phase I tests for toxicity and Phase II establishes
efficacy over ranges of dosages. Phase III is the definitive assessment,
double-blind randomized controlled trials with up to 5,000 patients.
Phase IV involves surveillance for side effects after the drug receives
FDA approval for sale.
Only one of 10 drug candidates win final FDA approval, so the stakes
Science or Business?
Dr. William Gray, a family physician in Spokane, Wash., and an official
of the Association of Clinical Research Professionals, said Schering-Plough
must be guided by science.
“They don’t they have any obligation to fulfill any
social obligation very early in the testing of a new drug,”
he said. “The research team has to come up with a development
plan that is purely scientific and does not have to follow social
But Dr. Jacob Lalezari, an assistant clinical professor at University
of California, San Francisco, denounced the hepatitis drug’s
Phase II trial design as “bad science.” He said it was
a missed opportunity to add to the medical literature about a little-documented
“This is a business decision,” said Lalezari, who is
a supporter of the hepatitis activist movement and director of Quest
Clinical Research, which develops antiviral treatments. “If
black patients responded well or better they would want them in
Schering-Plough said Phase II trials will attempt to find the compound’s
optimal doses and determine if it makes interferon and ribavirin
treatments work better. All the Phase II volunteers had failed to
respond to existing treatments.
Patients who defined themselves as African Americans, Pickett said,
were excluded for fear the low dosage of interferon in combination
with the new drug could “generate mutations in the virus”
that made them resistant to future treatments. Black patients, he
said, were enrolled in another branch of the Phase II trial that
uses a high dosage of the new drug researchers believed had a better
chance of working.
“If they develop resistance to this therapy,” he said,
“there is no other therapy available.”
Schering-Plough’s clinical trial design caught the attention
of Karama Neal, who has a doctorate in genetics from Emory University
and has written extensively about the use of race in biomedical
She took part in a conference call this month with Pickett and other
Schering-Plough scientists. Neal voiced opposition to volunteers
“self-definition” of their race “because it’s
not possible to define this concept and group at a biological level.”
The University of Pennsylvania’s Caplan also panned “the
crude characterization” of race in the trial design.
James Learned of the national Hepatitis C Action & Advocacy
Coalition said the group wrote a letter to the FDA protesting the
clinical trial design. He called Schering-Plough’s claim of
safety concerns “a smoke screen” and that “we
would have had the same reaction if women were excluded or any race
were excluded, where we found no safety issue.”
Felix Khin-Maung-Gyi, a bioethicist at Chesapeake Research Review,
which evaluates clinical trials, said the controversy is an example
of the tough choices between ethical principles in the Belmont Report,
which guides human medical research in the United States.
According to Khin-Maung-Gyi, the hepatitis advocates are calling
for justice — the inclusion of African Americans to ensure
they are afforded the benefits of the research.
The drugmaker, he said, is exercising beneficence — a risk-benefit
analysis to minimize possible harm to clinical trail volunteers.
“If people died because they were not responding and we entered
them in the study anyway, you could appreciate the conflict,”
he said. “We should not just be all inclusive and disregard
all the other principles in Belmont.”
Schering-Plough’s Pickett and Learned, the activist, meanwhile,
both concede the controversy could have been defused with more extensive
disclosure of the clinical trial’s goals.
“It would have made a difference,” Learned said.
Even so, Pickett was stung by the suggestion the company was biased
against the very people who stand to benefit most of its new drug.
“It can have an impact on people of color who are infected
by these diseases. Yeah, I’m interested,” he said. “Yeah,
I was irritated. There are very few political things that catch
my attention. This one caught my attention.”
(Associated Press/The Star-Ledger)