zyprexa: FDA Wonders if Lilly Drug Data Were Accurate

[Guest guest]

Lilly seems to be setting the standard for Verstraeten-like dilutions of

data.

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April 25, 2007

U.S. Wonders if Drug Data Was Accurate

By ALEX BERENSON

http://www.nytimes.com/2007/04/25/business/25zyprexa.html

The Food and Drug Administration is examining whether Eli Lilly & Company

provided it with accurate data about the side effects of the antipsychotic

drug Zyprexa, a potent medicine that has been linked to weight gain and

diabetes.

The F.D.A. has questions about a Lilly document from February 2000 in

which the company found that patients taking Zyprexa in clinical trials

were three and a half times as likely to develop high blood sugar as those

who did not take the drug.

That document was not submitted to the agency. But a few months later,

Lilly provided data to the F.D.A. that showed almost no difference in

blood sugar between patients who took Zyprexa and those who did not.

The F.D.A. confirmed its inquiry in response to questions from The New

York Times. The agency said it had not yet decided whether to take any

action against Lilly.

“The F.D.A. continues to explore the concerns raised recently regarding

information provided to the F.D.A. on Zyprexa’s safety,” Dr.

Mathis, a deputy director in the psychiatry division of the agency’s

center for drug evaluation and research, said.

A Lilly spokesman, Phil Belt, said the company had rechecked its database

and found errors in the original statistics. The data submitted later was

accurate, Mr. Belt said.

But the 2000 document said that its figures had already been checked for

error. The Times disclosed the existence of the document in an article

last December.

The discrepancy between Lilly’s initial data and what it later submitted

came at a time when Zyprexa’s sales were soaring, even as some doctors and

foreign regulatory agencies were questioning the drug’s safety.

The F.D.A. has never concluded that Zyprexa causes diabetes more than

other widely used psychiatric drugs, although the American Diabetes

Association has.

Zyprexa remains Lilly’s top-selling drug, with $4 billion in worldwide

annual sales. But prescriptions in the United States have fallen nearly 50

percent since 2003 amid the safety concerns.

Zyprexa and other antipsychotics are intended to quell the hallucinations

and delusions associated with schizophrenia and to treat some cases of

mania.

The document from 2000 and others were provided to The Times by B.

Gottstein, a lawyer who represents mentally ill people he says are forced

to take psychiatric medications against their will.

Besides the F.D.A. inquiry, Lilly is facing federal and state

investigations into the way it marketed and promoted Zyprexa. The company

has already agreed to pay $1.2 billion to settle 28,500 lawsuits from

people who contend that they developed diabetes or other diseases after

taking the drug. At least 1,200 more lawsuits are pending.

Mr. Belt, the Lilly spokesman, said in a statement that the company

properly marketed Zyprexa and disclosed its side effects to the F.D.A. and

doctors.

“Lilly always cooperates fully with requests for information from the

F.D.A.,” he said, “and that includes any requests regarding information on

Zyprexa. Lilly is forthcoming with all relevant clinical data on all of

our products.”

Lawyers who represent drug companies said the F.D.A. largely depended on

the companies to be honest about the side effects of their drugs. With a

staff of fewer than 3,000, including support personnel, the agency’s drug

division oversees more than 12,000 prescription medicines and 400

nonprescription drugs.

In most cases, said W. Vodra, senior counsel at the law firm of

Arnold & Porter and a former F.D.A. associate chief counsel, it does not

perform detailed audits of clinical trials or independently check the

integrity of the data that companies send to it.

“There’s no way they could police the system with the resources they

have,” Mr. Vodra said. Companies provide the agency’s scientists with so

much information that “there is a point at which you can’t even think

about what they’ve given you,” he added, “let alone what’s behind that

stuff that they may not have given you.”

A. Dormer, a partner in the law firm of Hyman, Phelps & McNamara,

who represents drug companies, said that the companies did not have to

provide every analysis they performed to the F.D.A. “Companies do lots of

drafts of things,” Mr. Dormer said.

The Zyprexa document that has aroused the most interest at the F.D.A. is a

Feb. 21, 2000, paper in which Lilly scientists discussed whether Zyprexa’s

label should be changed to alert doctors of the risk of hyperglycemia, or

high blood sugar, associated with the drug.

The paper showed that 154 of 4,234 patients, or 3.6 percent, who took

Zyprexa in clinical trials developed high blood sugar. Only 1.1 percent of

patients who took a placebo developed the condition.

Doctors have said that difference is worrisome because most patients in

the clinical trials were taking Zyprexa for only a few weeks or months.

Untreated hyperglycemia can eventually lead to diabetes, a disease in

which the body’s insulin-producing cells die and patients lose the ability

to regulate their blood sugar. Diabetes is the sixth-leading cause of

death in the United States.

The data that Lilly provided to the F.D.A. was notably different from the

results discussed in the February 2000 paper, with the gap between the two

patient groups much narrower. The company told the agency that patients

taking Zyprexa developed high blood sugar at a 3.1 percent rate, while

those taking the placebo had a 2.5 percent rate.

Mr. Belt said that after the February 2000 paper, Lilly performed a final

quality check of the data and discovered that some patients had been

incorrectly included in the analysis, while others had been excluded.

“The original data referred to in the memo was a preliminary analysis, not

the final accurate analysis that was provided to the F.D.A., and is

therefore very misleading,” he said.

The Times reported in December on the existence of the February 2000

document, as well as other company documents and e-mail messages that

contradicted public statements by Lilly about Zyprexa’s risks.

Lilly has said that the documents and e-mail messages were taken out of

context and do not present a balanced view of Zyprexa’s risks and

benefits. A federal judge has criticized The Times for violating a

protective order that covered the documents.

*

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