Senate investigators criticize two Harvard researchers

Say pair did not fully reveal pay from drug firms

NEW YORK - 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 Biederman, 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 Grassley's investigators. But even these amended disclosures may understate the researchers' outside income because some entries contradict payment information from drug makers, Grassley found.

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

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, 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." Wilens and Spencer said in e-mailed statements that they thought they had complied with the rules.

John Burklow, a spokesman for the National Institutes of Health, said: "If there have been violations of NIH 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 NIH will not tolerate it."

The federal grants received by 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."

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

Grassley sent letters on Wednesday to Harvard and the National Institutes of Health outlining his investigators' findings, and he placed the letters along with his comments in The Congressional Record.

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 the medications improve children's lives over time, specialists 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 institute 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 require drug makers to disclose payments made to doctors, and 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.

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," 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 Grassley's interest, Harvard asked the researchers to reexamine their reports.

In the new disclosures, the trio's outside consulting income jumped but was still contradicted by reports sent to 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, Biederman received an NIH grant to study in children Strattera, an Eli Lilly drug for attention deficit disorder. Biederman reported to Harvard that he received less than $10,000 from Lilly that year, but the company told Grassley it paid Biederman more than $14,000 in 2000, Grassley's letter stated.