Just before delivering an invariably hilarious observation or withering riposte, the beloved late comedienne Joan Rivers was known to confront audiences with her much repeated catch phrase: “Can we talk?”
I am reminded of this because for years, the government and the pharmaceutical industry have engaged in a dance of sorts related to the very serious and important question of whether or not the industry may share with physicians and patients truthful, non-misleading scientific and medical information that relates to unapproved, new uses or is otherwise outside the bounds of the FDA approved label. At long last, based upon recent exchanges with members of the Congress and Court filings, the answer to Ms. Rivers’ rhetorical question in this case seems to be a resounding, “Yes, we can.”
I have written about this issue before, and you can find an earlier column here. Over the past decade, the government has investigated and compelled settlements that reach into the several billions of dollars from virtually all of the major pharmaceutical companies, including Bristol Myers Squibb,
The government has long made clear that it does not care, particularly, if the new clinical information in question is truthful. It cares, deeply, about the prerogative of the FDA in its omnipotent role as regulator and if the information is outside the scope of the approved label. If it is, then it may be subject to challenge regardless of whether it represents a profound medical breakthrough or is merely an interesting anecdotal treatment regimen.
Beyond this, I have bemoaned the absence of an transparent process that rests upon the application of clear rules, as the FDA has been reluctant to elaborate on the basic restriction forbidding the promotion of unapproved uses, even in the face of rulings that admonished the agency for being overly restrictive and failing to regulate in a way that is properly sensitive to free speech principles. Following the 2012 decision of the U.S. Court of Appeals in Caronia, where the government’s conviction of a sales representative was overturned, senior FDA officials said that the agency was taking the First Amendment “seriously” and reviewing its rules on promotion to ensure that they were compatible with the Constitution.
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If you have ever defended a company that is alleged to have promoted improperly, it is hard to avoid the impression that you are living in a parallel universe from those sitting across the table threatening to take legal action against your client. The applicable Federal law, the Food, Drug & Cosmetic Act, does not refer explicitly to off label promotion, nor does it provide for criminal penalties or delegate to the FDA the authority to establish criminal penalties for marketing impropriety. The government has instead equated off label discussions with “misbranding,” a technical term that was formerly reserved for situations in which companies failed to properly include the FDA approved labeling in the package being sold. Officials have been reluctant to test their theory of liability in court, other than asserting in post-settlement press releases the legal doctrine that would properly lead to criminal penalties, never mind explaining how one might reconcile this position with the First Amendment to the United States Constitution that protects political and commercial speech.
Here’s an example from a Department of Justice press release concerning a settlement with
The government charged that [a J&J subsidiary] introduced the antipsychotic drug Risperdal into interstate commerce for an unapproved use, rendering the product misbranded. . . . Risperdal was approved only to treat schizophrenia. The information alleges that Janssen’s sales representatives promoted Risperdal to physicians and other prescribers who treated elderly dementia patients by urging the prescribers to use Risperdal to treat symptoms such as anxiety, agitation, depression, hostility and confusion. The information alleges that the company created written sales aids for use by Janssen’s ElderCare sales force that emphasized symptoms and minimized any mention of the FDA-approved use, treatment of schizophrenia. The company also provided incentives for off-label promotion and intended use by basing sales representatives’ bonuses on total sales of Risperdal in their sales areas, not just sales for FDA-approved uses.
This may sound nefarious, but let’s be clear: there is no existing FDA guidance that limits the physician audience as to whom companies may present information. There is no basis under the law for the Justice Department to contend that merely discussing symptoms that may be associated with an approved indication – as well as other indications – is unlawful. Indeed, the First Amendment does not allow the government to limit what one group of speakers (e.g., biopharmaceutical companies) may say, so long as the information is truthful and not misleading.
The government’s view has been plainly presented in the Millennium case. The relator claimant complained of clinical information culled from various peer-reviewed medical journal articles that were provided to sales representatives for promotional purposes. PhRMA says that there is nothing wrong with disseminating such articles to doctors, and indeed the FDA has itself issued guidance that generally permits it. However, DOJ asks the court to find that although truthful speech is indeed protected under the Constitution, companies must face liability if it is “reasonably foreseeable” that this speech will induce reimbursement for drugs that are later deemed by the government to be ineligible for coverage. In that case, a drug company is “aiding and abetting a crime” by spurring the submission of a false claim, though it seems to me that it is pretty darn remote (or as PhRMA says, “attenuated”) from the claims later submitted to result in liability. Interestingly, the government does not explain how an off label use of an approved product that is lawfully prescribed and medically appropriate can be rendered “false.”
I appreciate the clarity and directness of the government’s response to PhRMA in advancing the policy debate, but if the government really wants to limit reimbursement, why not just do so directly by denying the claim? Do we really need to rely upon prosecutors spending years on investigations that lead up to an elaborate negotiation during which companies capitulate and pay billions of dollars for allegedly violating the False Claims Act -- that is, a statute enacted in 1863 as a device to prevent the fraudulent sale of broken down mules to the Union Army? So long as physicians can prescribe freely in their practice of medicine, and the government and private payers continue to reimburse for products to be used off label yet deemed to be medically appropriate, how can we say that physicians and patients should not receive all relevant, truthful information about an approved product and its various uses? And how can it be that communicating such information is not protected speech, but is instead merely evidence of criminal “misbranding”? The Federal district court in California has an important opportunity to shed light on these questions.
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Where has the United States Congress been on this issue? Up to now, as with many other policy issues of some moment, our once estimably great deliberative body has been silent. But, it seems, no longer. Chairman Fred Upton (R-Michigan) and some of his colleagues on the House Energy & Commerce Committee want to talk about the off label issue. As part of Upton’s bipartisan (yes, really) 21st Century Cures initiative to advance biomedical innovation, the Health Subcommittee held a hearing this summer that deigned to explore the anomalies created when doctors can prescribe, and patients may be reimbursed, for off label uses, but companies may not talk about the implications of doing so. They are focused on identifying “barriers to ongoing evidence development and communication.”
In response to questions from Health Subcommittee Chair Joe Pitts (R-Pa.), Dr. Gregory Schimizzi, past President and member of the Board of Directors of the Coalition of State Rheumatology Organizations (CSRO), said he believed that the restrictions on off label information limit doctors’ ability to effectively treat certain patients, noting the possible but unexplored efficacy of using drugs to treat rare autoimmune diseases with small patient populations. “I do believe that the limitation on the exchange of information is hampering the delivery of healthcare to some of these patients especially in my sub-specialty. What needs to happen is that we need to have access to information that is locked up in vaults in pharmaceutical companies and locked up in [clinical study datasets].”
What could the Congress do? It could direct the FDA to establish a new pathway under which truthful information outside the scope of the approved label would be able to be discussed with physicians. Dr. Schimizzi suggested in the Subcommittee hearing that the Congress require “the FDA to develop standards for qualifying [previously reviewed] data through a public process, to expand the current process of review of materials beyond what is included in the package inserts, to also cover other key data such as subpopulation, pharmacoeconomic or comparative cost data and to ensure a timely review process for such information.” The Congress also could simply declare that the FDA may not regulate the communication of truthful information, and that may (or may not) limit the Justice Department’s determination to apply the False Claims Act to cases where off label prescribing is prevalent.
Regardless of approach, Chairman Upton plans to introduce an omnibus reform bill in the new Congress. If the off label issue is addressed, it would represent a historic change in attitude and behavior within the United States government that would clearly have significant implications for the way in which the FDA regulates drug, biotechnology and device company communications. This will not necessarily spur biomedical innovation, but it will be very good news for practicing physicians and patients suffering from disease or illness where the path to a cure is not so straightforward and requires access to all existing clinical information.
