Food and Drug Administration (FDA) Commissioner Dr. Margaret Hamburg announced in a 69-page decision that the agency would withdraw the biologic medicine Avastin as a treatment option for women with metastatic breast cancer.
Avastin (bevacizumab) is an injectable cancer medication manufactured and marketed by Genentech. Avastin blocks a protein that is important for the formation of blood vessels and is thought to work by preventing the formation of new blood vessels that feed cancer tumors.
Commissioner Hamburg’s decision will not affect Avastin’s approved indications for se in colon, lung, kidney, and brain cancers, and Avastin will remain on the market. As a result, physicians will be free to prescribe Avastin off-label for metastatic breast cancer.
The controversy surrounding Avastin for use in metastatic breast cancer came to a climax this past summer when FDA’s advisory committee held an “appeal” hearing concerning its recommendation that Avastin no longer be indicated for the treatment of breast cancer.
Despite the committee’s announcement and the June 2011 public hearing, the Center for Medicare and Medicaid Services (CMS) announced that Medicare will continue to pay for Avastin when used to treat breast cancer. According to a CMS spokesperson: “[t]he drug will still be on the market, doctors will still be prescribing it, and [CMS] will continue to pay for it,” adding that CMS often pays for off-label uses of drugs.
According to a recent article from the Food and Drug Law Institute (FDLI), CMS’ announcement confirms what drug manufacturers have long argued in the context of civil False Claims Act (FCA) litigation involving claims for “off-label promotion”: Medicare coverage is not driven by FDA approval, but rather is—and should be—based upon physicians’ professional determinations that a given drug is reasonable and necessary” for use by a particular patient for a specific indication.
The article asserted that, “CMS’decision to continue to provide reimbursement for breast cancer patients using Avastin also stands in contrast to legal and policy positions adopted by the Department of Justice (DOJ) in FCA cases involving promotional practices.”
CMS’ Position Inherently Conflicts With DOJ’s Position In Recent FCA Investigations and Litigation
CMS’ assertion that Medicare will continue to cover Avastin regardless of FDA’s decision—and regardless of an FDA finding that there is insufficient scientific evidence to support Avastin’s use in breast cancer—confirms that neither of these factors is dispositive of whether the use is medically “reasonable and necessary,” i.e., eligible for Medicare coverage by statute.
The article recognized that, “CMS’ position is consistent with the argument that pharmaceutical and medical device companies have long made (with limited success) in FCA investigations and litigation: that neither the off-label status of a particular use nor the quantum of scientific support for that use determines whether the use is properly reimbursable under Medicare’s “reasonable and necessary” standard.”
Accordingly, the authors asserted that, “the absence of FDA approval or specific scientific evidence supporting a particular use does not establish that those claims are “false” for purposes of FCA liability.” As the authors explained, “This argument goes to the very heart of the Government’s and qui tam relators’ ability to state—and prove—a claim under the FCA.”
That statute prohibits, in relevant part, “knowingly present[ing], or caus[ing] to be presented, a false or fraudulent claim for payment or approval.” If a particular claim for Medicare reimbursement is neither false nor fraudulent, it cannot provide the predicate for an FCA violation. DOJ, however, has opposed this argument when raised by FCA defendants.
For example, the article discussed the case United States ex rel. Strom v. Scios, Inc., in which DOJ alleged that Scios, Inc. violated the FCA by promoting the drug Natrecor for use in serial, scheduled outpatient infusions when Natrecor was only approved by FDA for intravenous treatment of patients with acutely decompensated congestive heart failure who have dyspnea at rest or with minimal activity. DOJ alleged that during the period at issue, “serial, scheduled outpatient infusions of Natrecor were not eligible for payment by Medicare because this off-label use was neither ‘reasonable and necessary,’ nor ‘medically accepted.’”
As the authors noted, “According to DOJ, the use failed to meet Medicare’s statutory standard because “the use was not supported by any credible study showing that the serial outpatient infusions were effective.” DOJ alleged the claims were “false because the off-label use is not covered” by Medicare.”
Almost by definition, a use is off-label precisely because there is insufficient evidence to support its approval by the FDA. If the mere lack of conclusive evidence were sufficient to establish falsity, the article explained that “there would be no such thing as a legitimate off-label claim – much less a regulatory framework in which offlabel uses are an ‘accepted aspect of a physician’s prescribing regimen.’”
Scios further argued that the scenario described in the Complaint is typical in the off-label context: “lacking data from a Phase III, double-blinded, placebo-controlled clinical trial, 4,000 physicians nonetheless determined— more than 170,000 times, based on their own first-hand observations of patients’ actual responses to the drug— that serial infusions of Natrecor were reasonable and necessary for the treatment of chronic heart failure.”
As the article noted, “This argument espoused the principle that CMS appears to have embraced in its recent announcement regarding Avastin coverage: individual physician judgments determine whether particular uses are “reasonable and necessary.”
Nevertheless, the court rejected Scios’s argument finding that “[b]ecause the [Medicare] statute permits reimbursement only for ‘reasonable and necessary’ treatments . . . a prescription of Natrecor in a context where it is not ‘reasonable’ or ‘necessary’ would be statutorily ineligible for reimbursement. This satisfies the FCA’s requirement of a ‘false’ statement.”
In reaching this conclusion, the authors noted that “the court appears to have relied, at least in part, on the Government’s allegations that Scios overstated the nature of the available scientific evidence to the physicians who prescribed Natrecor for outpatient infusions. DOJ’s briefs in Strom, however, do not rely on any alleged misrepresentations on the part of Scios. Rather, DOJ argues that the alleged lack of scientific evidence, in and of itself, means that claims for Natrecor for outpatient infusion could not have been “reasonable and necessary” and therefore were not eligible for reimbursement by Medicare.”
But as the authors explained, “CMS’ announcement regarding Avastin, however, highlights the flaw in DOJ’s theory: neither FDA approval nor the quantum of available scientific evidence, in isolation, determines Medicare coverage.”
DOJ’s Position Overlooks the Key Role of Physicians
The FDLI article asserted that, “DOJ’s briefs in Strom improperly ignore the central role that physicians and other health care providers play in determining whether the specific use of a given drug or medical device is “reasonable and necessary” for an individual patient, based upon each patient’s unique circumstances. Under Medicare’s reimbursement scheme, however (and as CMS’ announcement regarding Avastin confirms), that determination does, and should, control.”
To further this argument, the authors pointed to the U.S. District Court for the Southern District of Texas, which recently recognized this principle in two FCA cases involving allegations of off-label promotion by two medical device manufacturers. In U.S. ex. rel Bennett v. Boston Scientific Corporation and U.S. ex rel. Bennett v. Medtronic, Inc., a qui tam relator alleged that medical device manufacturers unlawfully promoted the use of surgical ablation devices to treat atrial fibrillation.
The authors noted that, “The relator further asserted that the defendants’ alleged off-label promotion “caused physicians and hospitals to submit claims to the government falsely stating that the use of the [devices at issue] was ‘reasonable and necessary’ or ‘medically necessary,’” but that the use of the surgical ablation devices to treat atrial fibrillation could not be medically necessary because the device was not FDA approved for such use.
In separate opinions, the court granted the defendants’ motions to dismiss, finding among other things that “[t]he decision on medical necessity is made by individual physicians exercising independent professional judgment based on the knowledge of their particular patients. The cases recognize that off-label use of a drug or medical device is distinct from a medically unnecessary use of that drug or device.”
The authors explained that, “While scientific evidence (or the lack thereof) may be determinative in certain instances, in others, a physician may decide that a particular off-label use of a medical device or drug is reasonable and necessary based upon his or her own observations or based on conversations with other physicians. In either case, the physician’s determination controls whether the use is reimbursable under Medicare.”
DOJ’s Wrongful Theory Has Significant Impact for FCA Defendants
The article noted that, DOJ has failed to respect and follow CMS’ policy as to how coverage determinations are made and “because DOJ is responsible for litigating FCA cases and prosecuting criminal off-label promotion cases, DOJ’s flawed theory has a real and substantial impact for pharmaceutical and medical device manufacturers.”
For example, the authors noted how “DOJ possesses enormous leverage to demand settlements reaching into the millions, and sometimes billions, of dollars in cases involving alleged off-label promotion,” because “the FCA provides for both treble damages and statutory penalties for each false claim allegedly presented.” Consequently, “DOJ’s financial threats are coupled with the potential for exclusion from participation in federal health care programs as well as FDA debarment.”
The article noted that, “These pressures frequently force pharmaceutical and medical device manufacturer defendants to settle FCA cases in order to resolve claims that they have committed “fraud” against the federal government by allegedly promoting their products for uses that are not approved by FDA.”
Ultimately, the authors noted that, “DOJ, both in legal briefs and in public statements, frequently equates alleged off-label promotion with fraud, without identifying allegedly false or misleading actions on the part of manufacturer defendants. CMS’ recent announcement regarding Avastin, however, underscores that Medicare coverage turns on a particular physician’s determination, in his or her independent medical judgment, that a specific use is “reasonable and necessary” for a given patient.”
Viewed in this light, the authors asserted that, “it is clear that claims for Medicare reimbursement are not “false or fraudulent” simply because FDA has not found sufficient scientific evidence to approve the underlying use.” Instead, the authors maintained that “it is inherently unjust for DOJ—in its role as the FCA enforcement agency—to continue to claim that manufacturers are committing “fraud” when its sister agency, CMS, knowingly pays for the off-label use underlying an FCA enforcement action.”