The New York Times has continued its series about how Eli Lilly and Co. marketed its best-selling anti-psychotic drug, Zyprexa (olanzapine). Yesterday it published an article suggesting that Lilly suppressed data that suggested a relatively high rate of adverse effects from the drug, while releasing data that made the drug appear safer:
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.A few days earlier, the Times had published an editorial on Lilly's marketing of Zyprexa.
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 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.
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.
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.
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.
It was bad enough when studies showed that the newest and most heavily promoted drugs for treating schizophrenia weren’t worth their high cost. Now the disturbing tale of their excessive use has taken a tawdry turn with revelations that Eli Lilly, a pharmaceutical giant, has consistently played down the risks of its best-selling antipsychotic drug, Zyprexa, and has promoted it for unapproved uses.Meanwhile, it was widely reported that Bristol-Myers-Squibb had agreed to settle charges having to do with problems with its sales and marketing practices, particularly of its big-selling atypical anti-psychotic drug, Abilify (ariprazole). Again, from the New York Times report:
Although Lilly says the documents present an inaccurate picture, they offer persuasive evidence that the company engaged in questionable behavior to prop up its best-selling drug, which creates almost 30 percent of Lilly’s revenue.
Bristol-Myers Squibb has reached a tentative agreement to pay $499 million to settle a federal investigation into illegal sales and marketing activities from the late 1990s through 2005, the company said yesterday.
That settlement, and separate special charges the company also announced yesterday, would wipe out Bristol-Myers fourth-quarter profit.
Bristol-Myers, based in New York, declined to disclose which years, which drugs and which practices the tentative agreement covers. But Jeff Macdonald, a company spokesman, confirmed previous reports that one product involved was the antipsychotic drug Abilify, one of the company’s best sellers.
Bristol-Myers said it also expected to sign a corporate integrity agreement with regulators in the Health and Human Services Department who monitor industry compliance with federal insurance programs.
The antipsychotic drug Abilify covered in the settlement has become the company’s best-selling product outside of its flagship cardiovascular group....
There is increasing reason to fear that the basis of much current thinking about the management of major psychiatric disorders, particularly schizophrenia, is on very shaky ground. More and more of the information that pharmaceutical companies have provided to physicians appears to be dubious. And very recently, allegations surfaced that pharmaceutical companies got far too cozy with state mental health departments to develop treatment algorithms for major psychiatric disease that emphasized the use of the newest, most expensive drugs, even though it is no longer clear that these drugs are so much better than older and cheaper treatments (see post here). Note that these Texas Implementation of Medication Algorithms (TIMA) pushed five new atypical anti-psychotic drugs for schizophrenia, including Abilify and Zyprexa.
To take the best possible care of each patient, physicians (and patients) need maximally accurate and unbiased information about the performance of drugs, devices, and diagnostic tests. It may be in the financial interests of companies that make such products to gimmick the data in their favor, but such manipulation can hurt patients, and surely is an unheralded reason for the continuing rapid rise in health care costs.
It is high time to get pharmaceutical, biotechnology, and device companies out of the business of the clinical testing of their own (or competitors') products. Let these companies sponsor the basic biology research needed to develop innovative new products. Clinical research on patients to evaluate these products should be done by organizations and researchers with no horse in the race.