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December 21, 2006

Disparity Emerges in Lilly Data on Schizophrenia Drug


For at least a year, Eli Lilly provided information to doctors about the blood-sugar risks of its drug Zyprexa that did not match data that the company circulated internally when it first reviewed its clinical trial results, according to company documents.

The original results showed that patients on Zyprexa, Lilly’s pill for schizophrenia, were 3.5 times as likely to experience high blood sugar levels as those taking a placebo, according to a February 2000 memo sent to top Lilly scientists. The memo is one of hundreds of internal Lilly documents provided to The New York Times by a lawyer in Alaska who represents mentally ill patients.

But the results that Lilly eventually provided to doctors until at least late 2001 were very different. Those results indicated that patients taking Zyprexa were only slightly more likely to suffer high blood sugar as those taking a placebo, or an inactive pill.

Another Lilly report, from November 1999, shows that Lilly found after examining 70 clinical trials that 16 percent of patients taking Zyprexa for a year gained more than 66 pounds.

The company did not publicly disclose that figure, instead focusing on data from a smaller group of clinical trials that showed about 30 percent of patients gained 22 pounds.

Weight gain and high blood sugar are important risk factors for diabetes, and the question of whether Zyprexa causes diabetes has been a subject of scientific debate for several years.

Lilly says no link has ever been proven.

In response to questions about the difference between its first view of the data and its subsequent public description, Lilly issued a statement yesterday saying that the later figures were accurate and the information in February 2000 was out of context.

In yesterday’s statement, the company said that after the February 2000 memo, it re-examined its clinical trial results and found errors in its “final, standard quality check of the data.”

But the February 2000 document, which is labeled “Confidential,” does not indicate that the figures it contains are preliminary. In fact, in a footnote, it explains that the data exclude patients “from whom there was a probable lab error.”

A separate document from November 1999 includes handwritten figures identical to those from the February document, with additional detail about the increases in blood sugar that patients suffered.

The revised figures were shared with the Food and Drug Administration, Lilly said. It did not say whether it had ever disclosed the initial data to the F.D.A.

The F.D.A. did not respond to requests for comment yesterday.

The 2000 memo indicates that it was prepared as Lilly considered changing Zyprexa’s prescription label to provide doctors with more information about the drug’s potential to raise blood-sugar levels.

The issue was crucially important to the sales prospects of Zyprexa, which was introduced in 1996. Psychiatrists were already increasingly aware by 2000 that Zyprexa caused severe weight gain in many patients.

“In 1999, we already were thinking this drug causes weight gain — that’s clear — and there could be a lot of other metabolic consequences of that,” Dr. David N. Osser, a psychiatry professor at Harvard University, said yesterday. “The weight gain itself is a known risk factor for diabetes.”

The February 2000 memo was prepared as background for a meeting of Lilly scientists to the possible changes for Zyprexa’s label.

According to the memo, Lilly scientists initially wanted to propose a relatively straightforward statement on the label that high blood sugar had been observed in patients taking Zyprexa in clinical trials. That change was never made.

Lilly’s analysis in early 2000 came at a time when some doctors and regulatory agencies were beginning to question whether Zyprexa could cause increases in blood sugar or diabetes. Although Lilly says that no link between Zyprexa and diabetes has ever been proven, the American Diabetes Association found in 2004 that Zyprexa was more likely to cause diabetes than other, similar drugs.

Zyprexa is by far Lilly’s best-selling product, with $4.2 billion in sales in 2005, which represented 30 percent of Lilly’s overall revenue. Zyprexa’s active ingredient is a potent chemical that binds to receptors in the brain to reduce the hallucinations and delusions associated with schizophrenia and acute bipolar disorder. About two million people worldwide took Zyprexa last year.

At the February 2000 meeting for which the memo was prepared, the agenda was to discuss Zyprexa’s tendency to cause high blood sugar, which is medically known as hyperglycemia.

According to the memo, Lilly had reviewed data from its clinical trials and found that “the incidence of treatment-emergent hyperglycemia in olanzapine group (3.6%) was higher than that in the placebo group (1.05%).” Olanzapine is the generic name for Zyprexa.

But when Lilly subsequently discussed the clinical trial results with doctors, it used a different comparison. Lilly told doctors that Zyprexa had caused 3.1 percent of patients — not 3.6 percent — to have high-blood sugar. And it said that 2.5 percent of patients on the placebo — not 1.05 percent — had high-blood sugar. As a result, the rates of high blood sugar in the two groups seemed almost identical in the revised data.