US: Researchers Fail to Reveal Full Drug Pay

Publisher Name: 
The New York Times

A world-renowned Harvard
child psychiatrist whose work has helped fuel an explosion in the use
of powerful antipsychotic medicines in children earned at least $1.6
million in consulting fees from drug makers from 2000 to 2007 but for
years did not report much of this income to university officials,
according to information given Congressional investigators.

By failing to report income, the psychiatrist, Dr. Joseph Biederman, and a colleague in the psychiatry
department at Harvard Medical School, Dr. Timothy E. Wilens, may have
violated federal and university research rules designed to police
potential conflicts of interest, according to Senator Charles E. Grassley, Republican of Iowa. Some of their research is financed by government grants.

Like Dr. Biederman, Dr. Wilens belatedly reported earning at least
$1.6 million from 2000 to 2007, and another Harvard colleague, Dr.
Thomas Spencer, reported earning at least $1 million after being
pressed by Mr. Grassley's investigators. But even these amended
disclosures may understate the researchers' outside income because some
entries contradict payment information from drug makers, Mr. Grassley
found.

In one example, Dr. Biederman reported no income from Johnson &
Johnson for 2001 in a disclosure report filed with the university. When
asked to check again, he said he received $3,500. But Johnson &
Johnson told Mr. Grassley that it paid him $58,169 in 2001, Mr.
Grassley found.

The Harvard group's consulting arrangements with drug makers were
already controversial because of the researchers' advocacy of
unapproved uses of psychiatric medicines in children.

In an e-mailed statement, Dr. Biederman said, "My interests are
solely in the advancement of medical treatment through rigorous and
objective study," and he said he took conflict-of-interest policies
"very seriously." Drs. Wilens and Spencer said in e-mailed statements
that they thought they had complied with conflict-of-interest rules.

John Burklow, a spokesman for the National Institutes of Health,
said: "If there have been violations of N.I.H. policy - and if research
integrity has been compromised - we will take all the appropriate
action within our power to hold those responsible accountable. This
would be completely unacceptable behavior, and N.I.H. will not tolerate
it."

The federal grants received by Drs. Biederman and Wilens were administered by Massachusetts General Hospital,
which in 2005 won $287 million in such grants. The health institutes
could place restrictions on the hospital's grants or even suspend them
altogether.

Alyssa Kneller, a Harvard spokeswoman, said in an e-mailed
statement: "The information released by Senator Grassley suggests that,
in certain instances, each doctor may have failed to disclose outside
income from pharmaceutical companies and other entities that should
have been disclosed."

Ms. Kneller said the doctors had been referred to a university conflict committee for review.

Mr. Grassley sent letters on Wednesday to Harvard and the health
institutes outlining his investigators' findings, and he placed the
letters along with his comments in The Congressional Record.

Dr. Biederman is one of the most influential researchers in child
psychiatry and is widely admired for focusing the field's attention on
its most troubled young patients. Although many of his studies are
small and often financed by drug makers, his work helped to fuel a
controversial 40-fold increase from 1994 to 2003 in the diagnosis of
pediatric bipolar disorder,
which is characterized by severe mood swings, and a rapid rise in the
use of antipsychotic medicines in children. The Grassley investigation
did not address research quality.

Doctors have known for years that antipsychotic drugs, sometimes
called major tranquilizers, can quickly subdue children. But youngsters
appear to be especially susceptible to the weight gain and metabolic
problems caused by the drugs, and it is far from clear that the
medications improve children's lives over time, experts say.

In the last 25 years, drug and device makers have displaced the
federal government as the primary source of research financing, and
industry support is vital to many university research programs. But as
corporate research executives recruit the brightest scientists, their
brethren in marketing departments have discovered that some of these
same scientists can be terrific pitchmen.

To protect research integrity, the National Institutes of Health
require researchers to report to universities earnings of $10,000 or
more per year, for instance, in consulting money from makers of drugs
also studied by the researchers in federally financed trials.
Universities manage financial conflicts by requiring that the money be
disclosed to research subjects, among other measures.

The health institutes last year awarded more than $23 billion in
grants to more than 325,000 researchers at over 3,000 universities, and
auditing the potential conflicts of each grantee would be impossible,
health institutes officials have long insisted. So the government
relies on universities.

Universities ask professors to report their conflicts but do almost
nothing to verify the accuracy of these voluntary disclosures.

"It's really been an honor system thing," said Dr. Robert Alpern, dean of Yale
School of Medicine. "If somebody tells us that a pharmaceutical company
pays them $80,000 a year, I don't even know how to check on that."

Some states have laws requiring drug makers to disclose payments
made to doctors, and Mr. Grassley and others have sponsored legislation
to create a national registry.

Lawmakers have been concerned in recent years about the use of
unapproved medications in children and the influence of industry money.

Mr. Grassley asked Harvard for the three researchers' financial
disclosure reports from 2000 through 2007 and asked some drug makers to
list payments made to them.

"Basically, these forms were a mess," Mr. Grassley said in comments
he entered into The Congressional Record on Wednesday. "Over the last
seven years, it looked like they had taken a couple hundred thousand
dollars."

Prompted by Mr. Grassley's interest, Harvard asked the researchers to re-examine their disclosure reports.

In the new disclosures, the trio's outside consulting income jumped
but was still contradicted by reports sent to Mr. Grassley from some of
the companies. In some cases, the income seems to have put the
researchers in violation of university and federal rules.

In 2000, for instance, Dr. Biederman received a grant from the
National Institutes of Health to study in children Strattera, an Eli
Lilly drug for attention deficit disorder. Dr. Biederman reported to
Harvard that he received less than $10,000 from Lilly that year, but
the company told Mr. Grassley that it paid Dr. Biederman more than
$14,000 in 2000, Mr. Grassley's letter stated.

At the time, Harvard forbade professors from conducting clinical
trials if they received payments over $10,000 from the company whose
product was being studied, and federal rules required such conflicts to
be managed.

Mr. Grassley said these discrepancies demonstrated profound flaws in
the oversight of researchers' financial conflicts and the need for a
national registry. But the disclosures may also cloud the work of one
of the most prominent group of child psychiatrists in the world.

In the past decade, Dr. Biederman and his colleagues have promoted
the aggressive diagnosis and drug treatment of childhood bipolar
disorder, a mood problem once thought confined to adults. They have
maintained that the disorder was underdiagnosed in children and could
be treated with antipsychotic drugs, medications invented to treat schizophrenia.

Other researchers have made similar assertions. As a result,
pediatric bipolar diagnoses and antipsychotic drug use in children have
soared. Some 500,000 children and teenagers were given at least one
prescription for an antipsychotic in 2007, including 20,500 under 6
years of age, according to Medco Health Solutions, a pharmacy benefit
manager.

Few psychiatrists today doubt that bipolar disorder can strike in
the early teenage years, or that many of the children being given the
diagnosis are deeply distressed.

"I consider Dr. Biederman a true visionary in recognizing this
illness in children," said Susan Resko, director of the Child and
Adolescent Bipolar Foundation, "and he's not only saved many lives but
restored hope to thousands of families across the country."

Longtime critics of the group see its influence differently. "They
have given the Harvard imprimatur to this commercial experimentation on
children," said Vera Sharav, president and founder of the Alliance for
Human Research Protection, a patient advocacy group.

Many researchers strongly disagree over what bipolar looks like in
youngsters, and some now fear the definition has been expanded
unnecessarily, due in part to the Harvard group.

The group published the results of a string of drug trials from 2001
to 2006, but the studies were so small and loosely designed that they
were largely inconclusive, experts say. In some studies testing
antipsychotic drugs, the group defined improvement as a decline of 30
percent or more on a scale called the Young Mania Rating Scale - well
below the 50 percent change that most researchers now use as the
standard.

Controlling for bias is especially important in such work, given
that the scale is subjective, and raters often depend on reports from
parents and children, several top psychiatrists said.

More broadly, they said, revelations of undisclosed payments from
drug makers to leading researchers are especially damaging for
psychiatry.

"The price we pay for these kinds of revelations is credibility, and
we just can't afford to lose any more of that in this field," said Dr.
E. Fuller Torrey, executive director of the Stanley Medical Research
Institute, which finances psychiatric studies. "In the area of child
psychiatry in particular, we know much less than we should, and we
desperately need research that is not influenced by industry money."

AMP Section Name:Pharmaceuticals
  • 182 Health
  • 185 Corruption
  • 208 Regulation