January 5, 2011
Prescribing “off-label” means prescribing a medicine for a use for which it is not authorised. Pharmaceutical companies may not promote off-label use of their medicines, for good reason. There is not the same tested scientific base for off-label use as there is for authorised use.
Qualified doctors may prescribe off-label, on the basis of their own professional judgement or experience – the wisdom of doing so is a matter for them. Companies can make a lot of money from off-label use of their medicines. There is an obvious temptation here that is not always resisted.
One such case was Zyprexa, an anti-psychotic from Eli Lily, and in the same class of atypical anti-psychotics as Seroquel, the subject of my first post. In 2009, Eli Lily pleaded guilty to having promoted Zyprexa for off-label use between 1999 and 2001. Many other related cases, including patient class actions and cases taken by individual US states have been settled.
I’ve been looking at many of the documents released in these cases. Zyprexa was indicated (authorised) at the time in cases of Schizophrenia and Bi-Polar 1 Disorder.
In 2000, the company launched a campaign, called Viva Zyprexa, to market Zyprexa to primary care physicians (PCPs), such as GPs and front line doctors in hospitals. Market research indicated that many PCPs were not comfortable in dealing with schizophrenia and Bi-Polar 1 and preferred to refer patients to psychiatrists. The Viva Zyprexia campaign, which had its own company song (lyrics only, can anyone guess the tune? ) sought to redefine “how primary care physicians treat mood thought and behavioural disturbances” by establishing Zyprexa as a “safe proven solution for mood thought and behavioural disorders”. It seems to me that we are a long way here from schizophrenia and bi-polar.
Similar problems can be seen in other documents associated with the campaign. A pre-campaign strategy document referred to framing the discussion “around symptoms and behaviour rather than indications”. I don’t know what actually happened in the field but promoting a medicine on the basis of symptoms and not diagnosis is not just unscientific; it is truly dangerous.
A briefing document from around the same time declared that it was not intended to promote for non-approved indications “but rather to illustrate potential symptom and behaviour profiles for which Zyprexa represented a much-needed solution”.
Eight months into the campaign, an implementation guidance document contained three (modified) patient profiles that could be used in promotion. Bi-polar was mentioned for one of the patient profiles, but the key aim was to establish Zyprexa as a broad spectrum “safe proven solution for mood thought and behavioural disorders”.
In the guilty plea the company acknowledged to having, between September 1999 and March 31, 2001, “promoted Zyprexa in elderly populations as treatment for dementia, including Alzheimer’s dementia”. There was no admission or finding that the campaign strategy might have facilitated other off-label uses.
Later work, including work published by the company itself, indicated a significant risk of mortality among elderly patients treated with Zyprexa
As to the dates, the government contended that the off-label promotion continued past March 2001 but the company did not accept that. In the plea agreement the government agreed in effect not to take the matter further.
Among the documents I did find one complaint alleging promotion of off-label use in August 2001. From handwritten notes it seems that the company intended to contact the doctor concerned but I found no other references to this complaint in the documents that I have seen.
A Sales Force Guide from 2002 seemed to be different in tone and much more limited in scope than the material from the Viva Zyprexa campaign. If readers have any views on this document I will be glad to hear from them.
Tech Note: The link to the “Viva Zyprexa” campaign document above is slow The document is on a google.docs site because of formatting problems.Author : Jim Murray