Pfizer To Monitor Off-Label Drug Use Under Neurontin Settlement

Pfizer will provide periodic reports to the HHS Inspector General about off-label use trends for its products under the May 13 settlement of an investigation into the company's promotion of Neurontin .

Under a five-year corporate integrity agreement entered into as part of the ¹ settlement, the company will provide annual analyses of off-label use patterns and promotional messages to the IG.

The corporate integrity agreement is part of a $430 mil. settlement of state and federal investigations into Warner-Lambert's marketing practices for Neurontin (gabapentin).

The penalty is the largest ever for an off-label promotion case, and was the focus of the headlines announcing the settlement.

The corporate integrity agreement, however, is likely to be closely studied in the pharmaceutical industry as a potentially more significant landmark.

"Groundbreaking" Compliance Program

"Pfizer has agreed to institute a groundbreaking and model corporate compliance program that stretches across the relevant portions of the entire Pfizer company, thus setting a high standard for the industry as a whole in efforts to prevent and detect improper marketing," Associate U.S. Attorney General Robert McCallum said during a May 13 press conference.

The value of the agreement as a statement of the government's policy on off-label promotion, however, is limited.

Although Pfizer will take steps to "prevent and detect improper conduct," there is no clear definition of what constitutes "improper" promotional practices.

The conduct alleged in the charging documents filed in the case offer some examples of specific tactics used by Warner-Lambert that would clearly fall in the sphere of "improper" behavior (see ² (Also see "Warner-Lambert GMP Conviction Plays Role In Neurontin Case" - Pink Sheet, 17 May, 2004.)).

However, in the wake of the WLF vs. FDA First Amendment rulings, there is no longer a bright line between legal on-label promotion and improper off-label activities (³ (Also see "FDA Affirms Off-Label Dissemination Policy In Denial of WLF Petition" - Pink Sheet, 4 Feb, 2002.), p. 12).

FDA participated in the Neurontin investigation, but the agency kept a low profile in the announcement of the settlement.

Acting Commissioner Lester Crawford was quoted in the DoJ announcement of the settlement, praising the cooperation of FDA and DoJ, and declaring that "these fines and penalties demonstrate that there is a strong system in place for ensuring that companies comply with the laws that safeguard Americans."

However, the agency did not issue a separate press release on the settlement or participate in the press conference.

Off-Label Promotion Not Prohibited

Rather than adopt a prescriptive approach, the IG agreement directs Pfizer to adopt compliance policies (most of which are already in place), and to keep careful track of off-label trends.

The agreement does not prohibit off-label promotion, but rather requires Pfizer to "promote its products in accordance" with FDA requirements.

In fact, one requirement of the agreement indicates on its face that off-label promotion is legal.

Pfizer compliance policy documents are to include "methods for selling, marketing, promoting, advertising and disseminating information about off-label uses of Pfizer's products in compliance with all applicable FDA requirements," the agreement states.

The reporting requirements in the agreement also mean that there will be a burden placed on Pfizer to understand and explain sharp increases in off-label use of any of its products.

Spot-Checking Trends

Pfizer will provide the IG each year with "a list and explanation of all actively promoted Pfizer products and, if available from third parties, information about the estimated relative usage (e.g., the percentage) of those products for off-label purposes," the compliance agreement states.

The IG will select "up to three Pfizer products" from the list "to be the basis for a review of records reflecting the content of detailing sessions."

For each of the products, "Pfizer shall obtain commercially available non-Pfizer records reflecting the purported content and subject matter of detailing interactions between sales representatives" and health care professionals. Specifically, Pfizer will use "verbatims or similar records."

The review will focus on records for all detail visits for each product during one week (selected randomly) for each of the first three quarters of the year.

"Pfizer shall review the records obtained and shall identify any instances in which the records appear to indicate that [employees] may have discussed and/or disseminated information about off-label uses."

Pfizer "shall make findings based on its review...and shall take any responsive action it deems necessary," including collecting "additional factual information about the circumstances," the agreement states.

The agreement notes that the IG has already selected the first three products for Pfizer to review.

Praise For Pfizer

The approach taken under the consent agreement in part reflects the prosecutors' confidence in Pfizer's in-house compliance standards.

The settlement agreement specifies that the conduct at issue was the responsibility of Warner-Lambert and took place in 1995 and 1996. The original complaint was filed against Warner-Lambert just before the company was acquired by Pfizer (⁴ , p. 3).

"There is evidence that Pfizer took steps intended to prevent" the off-label promotion "once it acquired Warner-Lambert," McCallum said.

Pfizer had already signed a CIA in 2002 as part of a $49 mil. settlement of Lipitor price reporting under the Medicaid program. Specific requirements included monitoring and reporting on managed care contracts (⁵ (Also see "Pfizer To Audit Managed Care Grants Under Lipitor “Best Price” Settlement" - Pink Sheet, 4 Nov, 2002.), p. 8).

The new agreement incorporates the 2002 CIA, but expands it significantly by requiring Pfizer to establish compliance policies in several new areas.

The enduring significance of the agreement, in fact, may be in the implied definition of promotional practices as including activities beyond traditional sales calls and advertising.

Specifically, the agreement covers reprint dissemination, continuing medical education, consulting arrangements, grant programs and even clinical trials.

Speakers Bureaus And CME

Pfizer is to maintain policies and procedures governing "the manner in which the Medical Information Department receives and responds to requests for information about off-label uses; the form and content of information disseminated by the Medical Information Department in response to such requests; and the internal review process for the information disseminated."

The compliance manual must also address "speaker meetings, advisory board meetings, and all other consultant arrangements." The "policies shall include requirements about the content and circumstances of such arrangements and events," the agreement states.

Similarly, Pfizer must have policies governing the "sponsorship or funding of continuing medical education programs."

Those policies "shall require the disclosure of Pfizer's financial support of the CME program and any financial relationships with faculty, speakers or participants at such CME program; shall require that the CME program be independent; and shall require that the CME program be balanced."

Finally, Pfizer is directed to have policies ensuring that its educational grant and research related activities comply with all federal requirements. Research-related activities explicitly include "clinical trials, market research or authorship of articles or other publications," the agreement states.

Most U.S. Employees Covered

The compliance policies will apply to "all officers involved in Pfizer's U.S. Pharmaceutical operations" as well as to "all employees of Pfizer Global Pharmaceuticals, the Corporate Finance Division, and the Pfizer Legal Division located in the U.S. and engaged in or having responsibilities directly relating to...promotional and product services related function."

That includes all Pfizer sales and marketing employees in the U.S., as well as many corporate and global functions that have responsibility for U.S. brands.

The agreement covers contractors, but explicitly exempts Pfizer's many co-promotion partners.