As we noted in our recent Pharmaceutical and Biotechnology Update,1 State Attorneys General have begun an aggressive campaign against off-label promotion utilizing their state consumer protection and/or unfair trade practices laws. Importantly, the settlements in three recent actions (now three in six months) spell out in substantial detail standards of conduct historically considered to be within the sole purview of the U.S. Food and Drug Administration (FDA). While these standards legally apply only to the parties in the settlements, they increasingly define conduct in an array of promotional areas that companies must be aware of to evaluate the adequacy of their current policies going forward.
At an audio Webinar on December 17, 2008, two key Assistant Attorneys General from Oregon and Illinois (two of the most active states) made some important points that the pharmaceutical industry must bear in mind. First, they predicted that these state actions would continue. Second, the cooperation between the states and the FDA is growing significantly and will continue to do so in the new Administration. Finally, they view the state off-label enforcement cases as complementary to the Federal False Claims Act cases of the last five years. The State Attorneys General believe that the act of marketing prescription drugs for unapproved indications violates their state consumer protection/unfair trade practices laws.2 Their clear bottom line — the role of the State Attorneys General will grow in importance for the enforcement of off-label promotion.
Pfizer settles claims related to promotion of Bextra and Celebrex
Following on the heels of the state settlements announced by Merck (May 20, 2008) and Eli Lilly (October 7, 2008), Pfizer announced on October 22, 2008, that it had entered into a $60 million settlement with 33 states and the District of Columbia to resolve claims related to the promotion of its Cox-2 inhibitors, Bextra and Celebrex.
The complaints in the Pfizer matter allege that Pfizer promoted Bextra for acute and surgical pain after the FDA rejected applications seeking approval for these indications. The complaints focus on Pfizer’s distribution of reprints and medical information that allegedly minimized or omitted discussion of the safety concerns associated with these uses. They also detail other conduct, including alleged misuse of continuing medical education, improper sales force incentives, abusive consultant practices, sampling violations, and misleading promotional campaigns.
In addition to fines, the judgment against Pfizer includes injunctive relief that applies to all of the company’s products. The judgment in large part echoes standards applied to Merck and Lilly, but also includes additional provisions driven by the particular facts of the case. These standards are instructive and provide guidance for companies in addressing key compliance issues. Nevertheless, given the constant state of flux of the industry and the anticipated announcement of new settlements in the upcoming months, companies’ response to any one settlement must be measured against the potential confusion generated by frequent policy changes.
As we discussed in our Update on October 27, 2008, the states are continuing to fill in the details about what they consider to be appropriate promotional and non-promotional conduct.
The Developing Baseline
The Pfizer state judgment repeats certain key standards from the preceding Lilly and Merck cases, suggesting the development of a baseline set of obligations that companies might expect when entering into state settlements related to off-label promotion. Specifically, Pfizer has agreed to the following policies:
- Continuing Medical Education (CME)
- Pfizer must require promotional speakers to disclose their relationship with the company to any CME provider or CME audience to whom that person may present if the product the speaker promoted for Pfizer is in the same therapeutic category as the subject of the CME program.
- The Grants Office must manage the approval of all CME funding requests without the involvement of sales and marketing.
- Pfizer shall comply with the ACCME Standards for Commercial Support.
- Pfizer is prohibited from funding CME if the company knows that a speaker at the CME has been a promotional speaker in the past twelve (12) months at a Pfizersponsored event related to the class of drugs to be discussed in the CME.
- Clinical Trial Disclosure – Studies must be registered and results submitted consistent with the FDA Amendments Act; however, Pfizer must register trials starting with those initiated after July 1, 2005.
- Advertising and Promotion Practices
- Pfizer’s promotional materials must comply with selected standards from FDA’s regulations on advertising.3
- Patient profiles used in promotional materials must be based on the FDAapproved indication.
- For Pfizer products indicated for pain relief, direct-to-consumer (DTC) television advertising must be delayed following initial approval, if requested by the FDA, up to a maximum of 18 months. For all Pfizer products, the company must submit DTC advertisements to the FDA for pre-review and modify ads consistent with FDA’s comments. Note, however, that Pfizer is only obligated to wait a reasonable time (not less than 45 days) for a response from the FDA. There is no such time limit in the preceding Merck judgment.
- Drug Samples
- Pfizer shall not disseminate samples with the intent of increasing off-label prescriptions. This is similar to a provision in the Lilly judgment requiring Lilly to distribute Zyprexa samples only to practitioners treating patients for approved product indications. The Pfizer settlement applies to all products, however.
- Authorship – All authors must satisfy the criteria outlined in the current International Committee of Medical Journal Editors (ICMJE) standards. New Obligations The Pfizer judgment also obligates the company to take (or refrain from taking) the following actions:
- Informed Consent – Pfizer must include in its model informed consent document:
- a statement that the study involves research, an explanation of the purposes of the research and the expected duration of the subject’s participation, a description of the procedures to be followed, and identification of any procedures that are experimental.4
- a description of any reasonably foreseeable risks or discomforts to the subject.5
- for research involving more than minimal risk, an explanation as to whether any compensation and an explanation as to whether any medical treatments are available if injury occurs and, if so, what they consist of, or where further information may be obtained.6
- Hospital Protocols/Standing Orders – Pfizer may not affirmatively seek inclusion of a product in hospital protocols or standing orders where the use would be off-label.
- Medical Information/Reprints – Pfizer may not distribute a reprint or medical information letter unless the information discussed is:
- about a scientifically sound clinical investigation or in the form of a unabridged reprint or copy of an article from a peer reviewed journal or reference publication.
- accompanied by a comprehensive bibliography of publications discussing adequate and well-controlled studies about the use.
- balanced with publications reaching a different conclusion, when applicable.7
- Preceptorships – Pfizer may not compensate physicians for preceptorships with sales representatives.
- Incentive Compensation – Sales representatives may not receive incentives or prizes as awards for increasing off-label product use.
- Submissions to Journals – Submissions of publications describing off-label uses must disclose that the studied use is not approved by the FDA.