Pfizer Bextra: Settling Big

Last week Pfizer announced a huge $894 million dollar settlement with patients, the Federal Government and States Attorney Generals over the marketing of Bextra and Celebrex.  33 states and the District of Columbia will share in a $60 million settlement and also receive several large concessions from Pfizer.

 

The judgment filed in Marion County Oregon Circuit Court will largely restrict Pfizer’s ability to deceptively promote any Pfizer products.

 

“This judgment, along with our other recent drug cases, should send a strong message to the pharmaceutical industry that we will not tolerate deceptive and misleading drug promotion,” Oregon Attorney General Hardy Myers said.  “The comprehensive injunctive relief obtained in this case is outstanding and addresses all concerns identified over five years of investigation.”

 

The 33-state investigation was initiated in 2003 to determine whether Pfizer and another drug company Pharmacia, subsequently purchased by Pfizer, misrepresented that their jointly sold “Cox-2” drug Celebrex was safer and more effective than traditional non-steroidal anti-inflammatory drugs (NSAIDS) such as Ibuprofen (Advil®) and Naproxen (Aleve®).  As the investigation proceeded, additional concerns were raised about Pfizer’s second generation Cox-2 drug Bextra.  Ultimately, the investigation concluded that Pfizer engaged in an aggressive, deceptive and unlawful campaign to promote Bextra “off label” for uses that had been expressly rejected by the Food and Drug Administration (FDA).

 

“Off-label” uses are uses not approved by the FDA. While a physician is allowed to prescribe drugs for off-label use, law prohibits pharmaceutical manufacturers from marketing their products for off-label uses.

 

In its complaint, the state alleged that despite the significant safety concerns that led FDA to reject a request to market high dose Bextra for acute and surgical pain, Pfizer conducted a systematic, multi-pronged “off-label” promotional campaign for these very indications by:

• Distributing hundreds of thousands of copies of a positive study from the denied application, as well as other positive studies relating to use of high dose Bextra, without distributing  or disclosing the negative study that was the basis for FDA’s rejection, or disclosing that FDA had expressly rejected approving Bextra for acute and surgical pain.

• Co-opting influential doctors with paid consultancies and lavish weekends at high end resorts.

• Distributing hundreds of thousands of samples of high dose Bextra to specialties whose only possible use for high dose Bextra was off-label.

• Providing prizes and otherwise encouraging sales representatives to promote Bextra off label.

• Using supposedly non-promotional Continuing Medical Education to promote Bextra off-label.

• Using imagery and language in advertisements that implicitly promoted Bextra off-label.

• Misrepresenting Bextra’s safety.

The complaint also alleged these efforts continued even after Pfizer completed a study that confirmed FDA’s reasoning for rejecting acute and surgical pain indications for Bextra.  This study ultimately contributed to FDA’s decision to withdraw Bextra from the marketplace, even at the low doses that had been previously approved.

 

Today’s judgment contains injunctive terms addressing all concerns raised during the investigation regarding both Celebrex and Bextra and applying to all Pfizer prescription drugs and biological products such as vaccines.

 

Below is a summary of what the settlement covered, it is quite comprehensive.

 

• Trial Results:  Shall submit as soon as practical all clinical trial results of all applicable trials after July 1, 2005 to the National Library of Medicine database www.clinicaltrials.gov

• Claims
  1. Agrees not to make any written or oral false claims
  2.  To be consistent with FDA approval

• Direct to Consumer Advertising
  1. For any pain product Pfizer will delay up to 18 months direct to consumer adverting for newly approved drugs if the FDA requests such a delay (effective 7 years)
  2. All DTC adverting campaigns for any Pfizer product will have to be pre-reviewed by the FDA.  If FDA does not respond within 45 days, Pfizer may run the advertisement but must still comply with any subsequent FDA comments about the advertisement and must notify the settling states and the District of Columbia that it is running the advertisement without FDA authorization (effective 8 years). 

• All communications on clinical trials, in regards to efficacy and safety
  1. Must accurately reflect the methodology,
  2. Not over present favorable data based on inadequate design and scope of trial, and
  3. Not be retrospective,
  4. Present the study as larger or more general experience
  5. Cannot use pooled data from various dissimilar studies

• Commercial Support of CME
  1. Shall comply with ACCME Standards of Commercial Support

2. Faculty must disclose their relationships with Pfizer
   • Orally and in writing
   • Including the nature, and purpose of his/her arrangement with Pfizer
     • If the product the faculty member promoted was in the same therapeutic category as the subject of the CME program
     • Within twelve months of work for or receiving compensation

3. Shall not provide funding of CME when Pfizer has knowledge at the time of the decision to fund CME that a speaker at the CME has also been a promotional speaker in the last twelve months (effective for 9 years)

4. The Medical Education Grants office shall manage all requests for funding
   • Decisions are to be theirs alone separate from sales and marketing
   • Approval may come from the CFO’s office or designated officials

5. Pfizer shall not use grants to advantage or promote products
   • Sales and marketing cannot initiate, coordinate, or implement grant applications on behalf of a customer or prescriber
   • Sales and marketing cannot be involved in selecting grantee or CME-funded speakers
   • Sales and marketing personnel shall not measure or attempt to track in anyway the impact of grants or speaking fees on the participating prescribers subsequent prescribing habits or patterns

6. Pfizer Sales and Marketing personnel shall not approve grant requests regarding products, nor attempt to influence the Pfizer Medical Education Grants Office to reward any customers or prescribers with grants for their prescribing habits, practices or patterns.

• Pfizer sponsored manuscripts  
  1. • The Author musthave made a substantial contribution
     • be involved in drafting or revising critically for important intellectually content
     • have final approval rights of the published version
     • For large multi centered trials the author should be identified

2. When submitting clinical trials relating to off-label use indications to a journal, Pfizer shall disclose to the journal that the FDA has not approved the drug for the indication that was subject of the clinical trial.

• Patient testimonials

Disclosure of generally expected performance and limited applicability of products must be included.

• Mentorships

Cannot compensate physicians for individual or observational teaching sessions in their offices in which sales reps participate.

 

• Clinical Trials Informed Consent

Must obtain informed consent forms from all study subjects:

• Includes an explanation of the research
• A description of the risks/discomforts
• An explanation of compensation or medical treatments available if the injury occurs

• Hospital Protocols
  1. Shall not seek inclusion into hospital protocols until the product has been approved by the FDA
  2. They may however disclose to insurance companies and other third party payers any information regarding the inclusion of a product in hospital protocols even if it has not been approved

• Sales Awards

They shall not award prizes or incentives to sales force for specifically increasing off label use of a product.     

• Dissemination of Off Label Information
  1. Not allowed to distribute information describing any off label use of a product if:
     • If such use has been submitted to the FDA and rejected or sent back for resolution of deficiencies
  2. Pfizer may disclose the information that it has or has not been submitted to the FDA for approval of that indication
  3. Medical Letters with off-label information distributed by Regional Medical Research Specialists
     • Must include a peer reviewed journal article or reference publication
     • Include a bibliography of clinical trials
     • Cannot include false or misleading statements
  4. Shall not disseminate a peer reviewed journal article or reference article describing off label uses to physicians who do not customarily prescribe the product.
  5. Pfizer can go back and get this provision changed if the FDA issues the final guidance for industry: Good Reprint Practices.

• Samples

Pfizer shall not distribute samples of a product with the intent of increasing off-label prescribing of the product.

 

According to Arnold Friede, Counsel of McDermott Will and Emory, an initial review of this settlement agreement suggests that it is the most comprehensive State AG settlement to date with a pharmaceutical company and incorporates elements of both the recent State AG settlements with Merck and with Lilly.  It appears to represent an unprecedented incursion by the State AGs into FDA's domain.  In this respect, it again shows that the State AGs are the new cops on the beat and that they will remain on patrol for as long as they perceive FDA is not adequately enforcing the law.

From reading this settlement is clear to me that the States Attorney General offices are very interested in helping the FDA enforce their rules.  With the addition of Direct to Consumer Advertising it's obvious the Attorney Generals clearly understand the way in which pharmaceutical companies work and are interested in seeing companies more compliant with the current rules.

Key Documents

Pfizer Settlement

Original Complaint