I thought long and hard about the title for this post and admit that I wanted it to be eye catching, as well as accurate for the subject matter being discussed. So why discuss the morality of off-label promotion? Well, despite hundreds (if not thousands) of legal briefs, articles, speeches, power point presentations, conference materials, etc., debating the legality, propriety and constitutionality of off-label promotion, not much has been said about the morality or ethics of a manufacturer’s decision to market, promote or encourage the off-label use of its products. The Government has strenously argued that any manufacturer off-label promotion, if permitted, would usher in a kind of “pre-1962″ era of unsafe and ineffective drug and medical device use. However, the better argument is that truthful and non-misleading off-label promotion should not only be allowed on free speech grounds, but when aimed at established, medically accepted uses, should be encouraged as both appropriate and ethical.
In its recent declaratory suit against the FDA, Par Pharmaceutical Inc., challenges the constitutionality of the agency’s off-label rules on free speech grounds, arguing that the FDA’s off-label regulations effectively prohibit the Company from discussing the approved indication of Megace-ES (i.e., to treat weight loss/wasting in AIDS patients) to physicians that Par knows prescribe the drug for well-known, medically accepted off-label uses (i.e., to treat weight loss/wasting in geriatric and cancer patients). For obvious tactical reasons, Par’s principal attack focuses on the absurdity of a regulatory scheme that chills even speech that the FDA has approved. However, Par also advances a subtle moral subtext regarding its inability to market Megace-ES to sick and vulnerable patients that badly need the drug for its off-label uses. In the latest round of briefs over the Government’s motion to dismiss Par’s suit, and whether Par is entitled to limited discovery from the Government in order to respond to the Government’s motion, both sides argue over whether Par did enough in seeking the FDA’s approval to use Megace-ES to fight weight wasting in geriatric and oncology populations. At the core of this argument is whether it would have been ethical or moral for Par to have conducted clinical trials in which some patients — particularly patients suffering from cancer — would have gotten placebo instead of the drug in order to generate the kind of data that usually leads to FDA approval for safety and efficacy. Par contends that it withdrew its application for FDA approval following the decision of an Institutional Review Board (IRB) that it would not approve a clinical study in which cancer patients would be given placebo. The Government counters that the IRB decision was limited to oncology patients, not geriatric patients, and, in any case, Par didn’t try hard enough to work with the FDA in finding an “alternative” path to approval.
Putting aside the particular facts of the Par litigation, we are left with some important questions. First, if it is ethically questionable to provide placebo to a very sick patient, where a treatment exists based on an established, medically accepted off-label use of a drug or device, then can the manufacturer’s promotion of that drug or device for such a use be wrong in the “moral” if not legal sense? Second, does the answer change if the patient doesn’t have cancer or some other serious or dangerous illness?
Hard-liners within the Government will most likely continue to toe the line and argue that a manufacturer misbrands a drug and violates the law when it intends for its drug or device to be used off-label, and will probably leave the ethical question to the treating physician. For those of us not employed by the FDA or Department of Justice, it might make more sense to draw the moral and legal line at cases involving cancer, ALS, or other terminal conditions. Such a position would bode well for Par and any other manufacturer with products used to treat life-threatening conditions. However, from my point of view, it would seem more logical and consistent to draw the line, not according to the seriousness of the condition being treated, but rather on whether the off-label use is an established, medically accepted use, as determined by its listing in approved medical compendia. The costs for such established, medically accepted off-label uses are usually reimbursed by Medicare, Medicaid and other federal healthcare programs, which (as in the case of Megace-ES), make it more difficult for the Government to argue that promotion of the off-label use is inappropriate. Drawing the line in this manner would provide clear guidance to physicians and manufacturers alike, strike the right balance between ethics and free speech on the one hand and the Government’s interest in ensuring drug and device safety and efficacy on the other, and advance patient welfare.