Friday, February 16, 2007

Zyprexa: Off-Label Promotion?

The document discussed in this post is called the “Zyprexa Primary Care Presentation”. It appears to be a transcript of a speech Mike Bandick, the Zyprexa Brand Manager, gave at the Eli Lilly National Sales Meeting on March 13, 2001.

It is important to note that Zyprexa is only FDA-approved for use in schizophrenia and bipolar disorder. The document appears to indicate that Bandick was encouraging salespeople to market Zyprexa for treating more than just these two conditions.

Bandick said:

We intend, quite simply, to redefine the way PCPs treat mood, thought and behavioral disturbances. We will continue to focus on symptoms and behaviors that PCPs see every day.

Later he said, referencing Zyprexa:

Broad symptom efficacy in mood, thought, and behavioral disturbances.

It seems curious that Lilly states they did not market Zyprexa for off-label purposes, yet the term “Mood, thought, and behavioral disturbances” seems a fair amount broader than schizophrenia and bipolar disorder. In addition, schizophrenia and bipolar disorder (especially bipolar I, which is the much more severe form of bipolar in comparison to bipolar II) are uncommon disorders. It is highly unlikely that primary care physicians would see patients with such conditions “every day.” However, it is certainly possible that a PCP may run across individuals who are manifesting much less severe “disturbances”, and it may well have been that it was this group, the patients who exhibited mild “mood, thought, or behavioral” symptoms, for whom Zyprexa was being marketed.

Bandick went on to discuss the case of Martha, which was discussed as being a case that seemed to much more strongly resemble dementia than schizophrenia or bipolar disorder. Martha was a hypothetical case that reps were said to have used in order to sell the benefits of Zyprexa to physicians. Bandick said:

Let me take a quick time out and make one quick comment on Martha. What’s the first thing you notice about Martha? She’s old! That does two things. First, it reinforces Zyprexa as a nursing home drug. Our mission is to build a primary care franchise, and let our long-term care team drive the nursing home business. Second, it limits the perception of behavioral disturbances – agitation, tension, anger, hostility all show up in primary care in a variety of packages. When you describe Martha, make her symptoms more prominent than her age.

It is certainly possible that there was a push to get PCP’s to recognize “agitation, tension, anger, [and] hostility” in their patients in a “variety of packages,” which could well mean off-label; the vast majority of people who struggle with these particular issues have neither schizophrenia nor bipolar disorder. At this point, I have not seen enough about the “long-term care team” to offer any intelligent idea as to their strategy, though I would assume that Martha may have been involved.

A few pages later, Bandick stated:

Emphasize patient benefits. And know the difference between a competitor and a “companion.” Drugs like Aricept and Zoloft belong to what we’re calling companion classes, drugs we augment rather than replace.

Aricept (donepezil) is FDA approved in the treatment of Alzheimer’s Disease, and Zoloft is approved in the treatment of depression and some anxiety disorders. Aricept is very rarely used in the treatment of schizophrenia, and Zoloft is not a sensible treatment for symptoms of either schizophrenia or bipolar disorder.

The idea to prescribe Zyprexa along with Aricept seems related to the case of Martha, who, as stated earlier, was a hypothetical patient discussed in sales materials, whose symptoms appear to resemble dementia (for which Aricept is frequently used) as opposed to schizophrenia or bipolar. Bandick’s speech lends credibility to the idea that Zyprexa was to be sold as an add-on for dementia treatment.

Also note that later in the same document, Bandick states that:

We expect approval this summer of an intramuscular formulation which will add two crucial words to our label: agitation and dementia.

It seems Lilly expected Zyprexa would be approved for dementia. Thus, it is possible that they were getting the word out early on Zyprexa for dementia, which would have not been allowable per FDA marketing regulations, although the approval never occurred.

Doctor-to-Doctor Marketing: Outside of sales reps, drug companies frequently use other practicing and/or academic physicians to help market their products. This is known as peer-to-peer marketing. In the current document, Bandick is quoted as saying:

Regarding peer-to-peer, we’ve just completed the second of two speaker training programs and have unleashed more than 130 psychs and PCP’s who are chomping at the bit to help you sell Zyprexa.

Bandick also stated:

We must utilize trained speaker to educate PCPs – not only on Geodon’s [a competitor medication] drawbacks, but especially on Zyprexa’s advantages and benefits to patients.

There is very likely nothing illegal about this practice, but having practicing and/or academic physicians act as salespeople can certainly raise conflicts of interest. While physicians may be more apt to believe other physicians as opposed to a sales rep, the line between sales rep and peer physician blurs significantly when physicians are paid and trained by a sponsoring company such as Lilly.

The document from which all quotes are cited is: Zy100041630.pdf and I thank Furious Seasons for hosting it as well as the other Zyprexa documents. Additional thanks to Alex Berenson of the New York Times, who first discussed Martha in an earlier article.

No comments: