A recent ruling in the Neurontin "whistleblower" case lays the groundwork for future prosecutions involving off-label promotions under the False Claims Act, Philadelphia Assistant U.S. Attorney Virginia Gibson said Oct. 2 during an audioconference sponsored by the Pharmaceutical Compliance Forum.

When investigating allegations concerning off-label promotions, prosecutors will view the "opinion as instructive to us," Gibson said. The opinion leaves room to file cases involving "truthful" off-label promotion, she maintained.

The assistant U.S. attorney negotiated the $355 mil. AstraZeneca settlement over violations of the False Claims Act relating to Zoladex marketing practices (¹ [A#00650250023], p. 31).

The "whistleblower" case, in which former Parke-Davis employee David Franklin is alleging that the company violated the False Claims Act by promoting Neurontin (gabapentin) for off-label uses, is pending in Massachusetts. U.S. District Judge Patti Saris denied Parke-Davis' motion for summary judgement Aug. 22.

Allegations against Parke-Davis (now Pfizer) include: false statements to physicians using contrived data; falsified data from clinical trials; a company-wide scheme to promote off-label use of the bad information; payments to physicians to promote off-label use; suppressing and manipulating study results; and publishing articles under the name of a physician when articles were actually written by the company (² Also see "IG Pharma Compliance Guide Has First Amendment Flaws, Attorney Says" - Pink Sheet, 28 July, 2003., p. 19).

The Boston U.S. attorney issued a "statement of interest" in the case in May but has not formally intervened.

Gibson noted that, under Judge Saris' opinion, off-label promotion can be prosecuted if it is "untruthful," "accompanied by kickbacks" or encouraging prescriptions for claims not reimbursed by Medicaid. Medicaid routinely covers off-label prescriptions for products included in major medical compendia.

"Relator is not required to present evidence that Parke-Davis lied to physicians about Neurontin's off-label efficacy or safety to induce them to prescribe Neurontin for uses ineligible under Medicaid," the opinion states.

"Though such evidence would be probative as to whether Parke-Davis caused to be presented false Medicaid claims, truthful off-label marketing (ineligible for federal safe harbors) and financial incentives like kickbacks would suffice," the opinion adds.

Judge Saris cited an earlier opinion that states, "the alleged FCA violation arises - not from unlawful off-label marketing activity itself - but from the submission of Medicaid claims for uncovered off-label induced by defendant's fraudulent conduct."

Gibson noted that Saris' opinion leaves open the question of whether cases can be brought over truthful off-label promotion in states that have the discretion to reimburse for off-label uses under Medicaid.

Judge Saris "went into an analysis in her opinion of those states who may have the discretion to reimburse for off-label prescriptions, and I think we really need to consider that aspect of the opinion for truthful off-label marketing," Gibson said.

According to Parke-Davis, 42 state Medicaid programs permit reimbursement for off-label, non-compendium drug uses, thereby making claims for Medicaid reimbursement for off-label Neurontin prescriptions in those states valid.

The opinion points to the Medicaid rebate statute, which says, "a state may exclude or otherwise restrict coverage of a covered outpatient drug if the prescribed use is not for a medically accepted indication."

Parke-Davis argues that the language "may exclude" indicates that the states have the option to "not exclude" coverage as well, Saris notes. However, Franklin maintains that the statute affords states discretion only within the category of "covered outpatient drugs," defined as being prescribed for a medically accepted indication, Saris adds.

"It is not clear which side gets the better of the statutory tail-chases-cat debate," the opinion states. "The court would appreciate an amicus brief from federal officials, providing the federal government's understanding of the extent to which the Medicaid statute empowers states to provide coverage of off-label, non-compendium prescriptions."

Saris notes that Parke-Davis concedes that eight states do not provide reimbursement for off-label prescriptions. "Thus, at best Parke-Davis' argument goes to the amount of damages, and does not provide a basis for summary judgement of no liability under the FCA," the opinion states.

Gibson outlined the types of evidence the Department of Justice would look for when pursuing allegations related to off-label promotions.

"A number of pieces of evidence would be obvious to us: financial incentives for off-label use only; failure to identify the company's funding for research for articles that it presents...in the guise of medical education; health consequences from off-label use that are not disclosed," Gibson said.

"We would look at a situation where...there was a very small market for the approved use...but there was a very large sales force. That would prompt us to look further," she said.

The prosecutor cited Genentech's settlement over off-label promotion for its growth hormone therapy Protropin as an example of a manufacturer who promoted its product with a sales force that was larger than required by the market size for its approved use.

Genentech plead guilty to promoting Protropin for children with idiopathic short stature when the product was indicated only for growth hormone-deficient children (³ Also see "GENENTECH ALLEGED PROTROPIN PHYSICIAN INDUCEMENT OF OFF-LABEL USE UNDER FDA INVESTIGATION; AGENCY HAS LIMITED AUTHORITY OVER FOUNDATIONS, KICKBACKS" - Pink Sheet, 22 August, 1994., p. 3). Lilly's Humatrope was approved for idiopathic short stature nearly a decade after the Genentech settlement (⁴ Also see "Lilly Humatrope Postmarket Plans: Voluntary Study, No Patient Registry" - Pink Sheet, 4 August, 2003. p. 36).

The DoJ would also "look at the role of the manufacturer in the prescribing activity at all levels, whether there were inducements, whether there were false statements," Gibson said.

"We would look at market research reports that might record a doctor's state of mind after the marketing meetings or record a physician's prescribing activity before and after conference that the manufacturer might host. We would look at whether inducements accompanied that, whether there were adequate disclosures about the off-label information presented at those conferences."

She added that prescription trends alone are "insufficient, but it does tell us that something is going on here."

Sidley, Austin, Brown & Wood Partner Paul Kalb, MD, predicted that False Claims Act cases involving off-label promotion will increase.

"We will likely see more enforcement activity, more litigation in the off-label area under the False Claims Act in the next five years," Kalb said. Unlike the FD&C Act, the False Claims Act includes a private right of action that encourages "whistleblower" suits, he noted.

Kalb suggested that prosecutors will not limit their focus to off-label promotions alone but will instead investigate manufacturers' general marketing practices.

"These cases...will likely not focus exclusively on off-label promotion," Kalb said. "We will be seeing cases in which the government uses the False Claims Act as a vehicle for attacking marketing practices."

Kalb suggested that off-label promotion for cancer drugs in particular should be held to a different standard. "If drugs are being used even for an unapproved use to potentially help save someone that has failed treatment for a lethal disease for other drugs, then it is very hard for me to understand the public policy behind a prosecution in that area."

Gibson agreed that off-label use of cancer drugs is a difficult area because the "reimbursement systems are maybe getting ahead of the FDA approval process...because physicians are prescribing for this drug and the committee for that state is allowing reimbursement for a particular off-label use."

Nevertheless, Gibson added, "we still will look at whether there is evidence of some kind of inducement, some kind of falsity in the marketing if it is off-label marketing that's occurring."

Abbott Regulatory Affairs Director-Advertising and Promotion Michael Misocky suggested that class action lawsuits are another potential area of liability from off-label promotion. "Certainly the plaintiff lawyers are out there looking for new targets following big tobacco....Some of them even monitor the FDA website for warning letters or untitled letters."

Because plaintiffs will look at all types of company communications, including emails and voicemails, "it's important in house that you get a handle on all of the activities that are going on, not just sitting around reviewing visual aids and promotional materials," Misocky warned.

Neurontin Ruling Is Guide For DoJ Off-Label Promotion Cases – Prosecutor

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