Eli Lilly: Settles Down with State AG’s

Yesterday Eli Lilly settled a consumer protection lawsuit on Zyprexa, one of their psychiatric drugs, for $62 million with 32 states, including California, Illinois, Florida, New Jersey, New York and Pennsylvania.

Under the agreement, Lilly said it has made “certain commitments'' for the next six years regarding Lilly's promotion, dissemination of medical studies, disclosure of clinical trials, funding of grants and continuing medical education relating to Zyprexa.

This lawsuit, along with several pending in 12 other states and a pending federal case, resulted from internal Lilly documents and email messages that appear to show that the company marketed Zyprexa for off label uses including dementia and mild forms of bipolar disorder.

There is also a history of the company failing to discuss potential safety and side effect issues with Zyprexa.  Zyprexa  promotes considerable weight gain and may predispose patients to development of diabetes.   This has cost the company $1.2 billion in patient settlements thus far.

The $62 million is the largest settlement in a state consumer protection case, larger than the $58 million settlement by Merck for Vioxx.

The settlement is sweeping and covers many aspects of Eli Lilly’s business including promotion, medical information, CME (Continuing Medical Education), speakers and consultants, samples and clinical research.

One new aspect of the settlement is that Lilly will have to disclose to the signatory Attorney General Offices a list of promotional speakers and consultants who were paid Lilly any taxable income in excess of $100 and a list of all titles of promotional presentations made.

According to Arnold Friede, Council for McDermott, Will and Emory "As in the Merck settlement of the Vioxx matter with the State AGs, the Lilly settlement with the State AGs on Zyprexa is further evidence that the State AGs have insinuated themselves as the new cop on the beat in implementing and enforcing requirements that have historically been in FDA's bailiwick."

The settlement is very technical, and nuanced. The bottom line is that for the next six years, Lilly will have to be very careful about how they market Zyprexa and all other products.

 There is a section (3) dedicated to the practice of CME, which adds additional definition for Eli Lilly to diligently keep sales and marketing separate from CME grants.

The following are some of the key points to the settlement agreement:

1.    Promotional Activities

a.    Lilly shall not make any written or oral claim that is false or misleading regarding Zyprexa

b.    For Six Years:

                                                  i.    Lilly shall not promote Zyprexa for off-label uses.

                                                ii.    Lilly shall not present patient profile types based on symptoms of the FDA approved indication unless

1.    The approved indications stated clearly

2.    Promotional Slide Kits

a.    Approved indications on same slide

b.    Shorthand reference to approved indication

c.    Promotional Material has a reference indicating the full constellation of symptoms and relevant diagnostic criteria in the DSMMD.

 

Bottom line:  End all off label promotion of Zyprexa, which Lilly isn't allowed to do in the first place.

 

2.    Dissemination of Medical Information

a.    In general terms content of off label use of Zyprexa shall not be false, misleading or deceptive

b.    Medical letters and references (Eli Lilly for Zyprexa)

                                                  i.    Medical has the ultimate responsibility for developing and approving content including any that may describe Off-Label information.

                                                ii.    Lilly shall not distribute any such materials unless

1.    Clinically Relevant information is included to provide scientific balance

2.    Data presented in unbiased, non promotional manor

3.    Distinguishable from sales aids or other promotional materials

c.    Sales and marketing shall not develop the medical content  of medical references or letters;  they are permitted to suggest topics

d.    Sales Reps cannot distribute medical letters or references

e.    Not permitted to knowingly disseminate any medical letter making false or misleading representation of Zyprexa or a competing product

f.     Request for Off Label Information

                                                  i.    Notification of requestor that request is for off label information

                                                ii.    Medical shall provide a specific, accurate, objective, and scientifically balanced responses (not off label promotion)

                                               iii.    The response has to include a “reasonable literature search”

                                               iv.    Non medical personnel may not respond to off label requests

                                                v.    They may respond orally

g.    Reprints

                                                  i.    Responsibility of Lilly Medical

                                                ii.    Accompanied by prescribing information

                                               iii.    Not used in a promotional manner

                                               iv.    Can only be distributed by Medical personnel except

1.    Extraordinary circumstances approved by the President of Lilly

2.    Clinical Necessity approved by each AG office

3.    State may prevent dissemination

                                                v.    Can contain incidental reference to off label information

h.    Healthcare Economic Information

                                                  i.    Must be based on competent and reliable scientific information

 

Bottom line: Eli Lilly has to be very careful on what their sales reps and medical staff disseminate or how they answer questions from healthcare providers.

 

3.    Continuing Medical Information

a.    Lilly shall disclose their CME grants on their registry at www.lillygrantsoffice.com and maintain them for two years on the site and available for five years to the AG’s offices

b.    Lilly Grant Office (LGO) shall manage all requests for funding.  Approval decisions shall be made by LGO alone and shall be kept separate from sales and marketing

c.    Lilly shall not use grants to promote Zyprexa

                                                  i.    Sales and Marketing shall not initiate, coordinate or implement grant applications on behalf of any customer

                                                ii.    Sales and Marketing shall not be involved in selecting grantees or CME funded speakers

d.    They shall not condition funding regarding grant requests regarding Zyprexa upon the requestors selection or rejection of particular speakers.

e.    Lilly shall not suggest, control or attempt to influence selection of the specific topic, title, content, speakers or audience for CME regarding Zyprexa consistent with ACCME guidelines.

f.     Lilly Sales and Marketing shall not approve grant requests regarding Zyprexa, nor attempt to influence the LGO to reward a customer or healthcare provider with grants for their prescribing habits, patterns or practices

g.    Contractual requirement for the CME providers to disclose financial support of the CME program, and any financial relationship with faculty and speakers.  Also require that the CME program identify the URL of the Lilly Grants website as a source of grant funding regarding Zyprexa

h.    After initial delivery of a CME program, Lilly shall not fund the same program, if it knows that the program’s speakers are promoting Zyprexa for off label uses.

 

Bottom Line:  Continue diligence around your CME program, continue to disclose your grants, make sure your providers do the same and follow the ACCME Standard for Commercial Support and PhRMA codes, and next years’ programs should be different than this year’s.

 

4.    Payments to Consultants and Speakers

a.    Lilly shall provide to each AG an electronic spreadsheet of all HCP Speakers and Consultants who were paid by Lilly any taxable income in excess of $100 for promotional speaking and/or consulting preformed for Lilly in the US.

                                                  i.    A list of all titles of promotional presentations made

                                                ii.    Total compensation for any consulting or promotional speaking fees

                                               iii.    Total number of promotional speaking events

                                               iv.    The state that the promotional speaker resides in

                                                v.    The state he gave the promotional presentation

b.    Any other compensation set forth in a 1099

c.    The information is due on or before July 1, 2009 for 1^st quarter 09, October 1, 2009 for 2^nd quarter and so one….

d.    Lilly will disclose to the speaker/consultant that that this information will be disclosed.

Bottom Line:  The states attorney generals will get Eli Lilly’s entire list of consultants and promotional speakers with no regard to product, to assist in further investigations (the gift that keeps on giving).

 

5.    Product  Samples

a.    Only sample to HCP whose practice is consistent with current product labeling

b.    If the HCP is not in the above group, they have to call an 800 number to ask questions and then they may be provided samples if appropriate.

Bottom Line: Samples only to those HCP’s that have FDA approved uses.

 

6.    Clinical Research

a.    Lilly will register all trials and results as required by the FDA

b.    Lilly will register all trials on Zyprexa from July 1, 2005

c.    When presenting clinical trial data for Zyprexa

                                                  i.    The following would be considered false and misleading

1.    Presenting favorable data or conclusions that is inadequate in design and scope to furnish support for such conclusions.

2.    Fails to meet statistical significance or fails to show range (confidence interval)

3.    Uses retrospective data to cite findings not supported by the study

4.    Presents information in a way that a larger or more general experience

5.    Uses statitiscs on numbers of patients or counts of favorable results or side effects derived from pooling data from various insignificant or similar studies to support a favorable conclusion.

Bottom Line:  This serves as a promise by Lilly that they will no longer present biased data or partial results (by not revealing data interpreted to be detrimental). They are also agreeing to maintain comprehensive clinical registry data on patient populations, efficacy and safety; and that this registry information will be transparently available for independent review and interpretation.  

This settlement serves as sincere apology for past sins, plus a guarantee that all future data generated on this drug will be subject to complete and objective analysis.

This settlement will have far reaching implications for the entire pharmaceutical and device industry and perhaps changes the landscape on what is expected in the future.

Reference Documents:

Lilly Press Release on Zyprexa

Lilly Settlement Agreement

Wall Street Journal Blog: Lilly Paying $62 Million to Settle State Zyprexa Investigations

 

AP: Eli Lilly settles Zyprexa inquiries in 32 states

 

CNN Money: Eli Lilly Settles 32-State Zyprexa Suit For $62 Million

 

NY Times: 33 States to Get $62 Million in Zyprexa Case Settlement

MWE White Paper on Merck Settlement