Unsettled Science Clashes with the Law

WASHINGTON, MAY 22, 2008 -- "Off-label prescribing"--that is, using a drug to treat a condition for which it has not been approved by the Food and Drug Administration (FDA)--is increasingly the cause of prosecutions and lawsuits brought against drug manufacturers. But off-label indications often become the standard of care for medical professionals after articles in peer-reviewed medical journals show that the drug is medically effective for another condition. On May 21, experts met at the American Enterprise Institute to discuss the current regulatory and legal framework that prevents manufacturers from disseminating this information that can advance public health. Having information about new uses of older drugs is especially important for patients who have exhausted all other medical remedies.

At the conference, AEI's John E. Calfee presented results from a new survey of 200 oncologists on off-label prescribing. The new survey updates a similar survey he conducted in 1997 with Lamar McGinnis. The new research shows that oncologists continue to prescribe off-label and do not believe the label indications are useful. More oncologists in the new survey than in the 1997 one indicated that they prescribe on-label, a development Calfee attributed to reluctance to prescribe off label due to recent reimbursement restrictions and bad publicity over off-label use.

AEI's Scott Gottlieb, a former senior official at the FDA, noted the importance of creating a policy environment that takes into consideration the benefits of off-label uses while constraining the dissemination of information that is not useful in a medical setting. While there have been some instances of pharmaceutical companies using unscrupulous marketing tactics to promote their products, in most cases, manufacturers carefully follow the letter of the law. Public health suffers when they are banned from sharing the new information with doctors. Gottlieb argued that state attorneys general and lawyers at the Justice Department should also make the distinction between positive and negative information-sharing in this setting and "look to the literature as criteria for what cases they go forward with."

Daniel Troy of Sidley Austin, the FDA's former chief counsel, explained that federal prosecutors have even pursued criminal charges that have not required them to show a false or misleading representation of information. Additionally, all of the pharmaceutical companies have thus far settled because of the high financial risk associated with going to trial and the risk of exclusion--the loss of the right to practice before the FDA. Companies' reluctance to go to trial prevents them from challenging the Justice Department and asserting the First Amendment argument for the dissemination of true and non-misleading information.

George Terwilliger of White & Case argued against using criminal law and civil enforcement mechanisms to enforce regulatory offenses. "It is easy to slide into a circumstance where prosecutors start filing in the blanks in regulation, where prosecutors are drawing the regulatory lines," he said, "and that, in my judgment, perverts the whole reason Congress set out to have an agency with regulatory expertise and gave it enforcement authority." John Osborn, a visiting research fellow at the University of Oxford, noted that the laws surrounding the dissemination of publications are perhaps purposefully unclear and that regulations must be clarified for manufacturers so that those that act in good faith are sure of their legal boundaries.

AEI's Ted Frank said that class action lawsuits are unsuitable vehicles for litigating off-label marketing cases: "Underlying causation allegations are inherently individualized and therefore unsuitable for class actions." If judges improperly certify classes and the suits survive the summary judgment motion, plaintiffs' attorneys can force manufacturers to settle cases regardless of merit. Frank also noted that broad consumer fraud laws provide a mechanism for attorneys to file claims against the manufacturers who are providing truthful marketing information, and, in some cases, litigants have sought liability for uses that are actually on the FDA-approved label.

Brian Anderson of O'Melveny & Myers explained that attorneys general often pursue these cases because they are high-impact lawsuits that provide them with good publicity, monetary awards for their states, and opportunities to reward political supporters. Anderson stressed that these lawsuits are often "reverse engineered"--that is, filed to see what the state can find during the discovery process when the evidence is not strong. In these cases, Anderson recommended that manufacturers "challenge the legal sufficiency of the lawsuits and force the state to defend often unprecedented applications of state law."

Kyle Sampson of Hunton & Williams noted that states are increasingly enacting their own false claims statutes and that as false claims actions on off-label usage increase, it "likely will result in an incoherent regulatory regime that, ultimately, will provide little benefit to the states while significantly increasing legal uncertainty and risk for the pharmaceutical industry." Mark Herrmann of Jones Day argued that off-label use should not be admitted into evidence in cases alleging medical malpractice unless the doctors' prescription was contraindicated.

James Beck of Dechert argued that the dissemination of truthful information about off-label uses is protected by the First Amendment. He said that the FDA should allow truthful speech while maintaining regulatory control through non-speech regulations, such as requiring manufacturers to submit guidance for FDA approval after a drug has reached a certain percentage of off-label use. Most pharmaceutical manufacturers would claim these studies required by FDA for new indications are too time-consuming and costly. But Beck suggested that since the drug is already on the market and it may be infeasible to perform a placebo-controlled study, the FDA could modify their standard for data for approvals of new indications.

--KRISTY HAWLEY

For video, audio, and more information about this conference, visit www.aei.org/event1725/.

Ted Frank, the director of AEI's Legal Center for the Public Interest researches liability reform, particularly product liability relating to pharmaceuticals, corporate litigation, and class actions and civil procedure. Scott Gottlieb and John E. Calfee examine how regulatory measures surrounding off-label marketing affect the public health, firms, and the medical community.

• Gottlieb has examined FDA guidelines on dissemination of information on unapproved uses of medical products.
• Calfee has examined the affect of direct-to-consumer advertising of prescription drugs.
• Frank is a regular contributor to the liability reform weblogs Overlawyered.com and PointofLaw.com.

For more information about AEI's Legal Center for the Public Interest, visit www.AEILegalCenter.org or contact Sara Wexler at sara.wexler@aei.org or 202.862.5820.

For more information about AEI's Health Policy Studies program, visit www.aei.org/health/ or contact Kristy Hawley at kristy.hawley@aei.org or 202.862.5920.

For media inquiries, contact Véronique Rodman at vrodman@aei.org or 202.862.4870.

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