May 13, 2005 North Carolina State University Off-Label Use and Product Liability: Basic Principles David L. Baumer, Ph.D., J.D., Attorney at Law, Professor of Law and Technology

May 13, 2005North Carolina State University Basic Principles The FDA regulates the manufacture, labeling, and promotion of drugs –In highly simplified terms, a pharmaceutical firm must obtain FDA approval to sell drugs. –In the NDA (New Drug Application) the applicant has to prove that the drug is safe and effective for various uses These uses become the labeled uses…the uses for which the tests have been conducted. Once a drug is approved by the FDA, various medical researchers and practicitioners may discover that such drugs have other valid (off-label) uses

May 13, 2005North Carolina State University FDA Jurisdiction –The FDA does not regulate the practice of medicine –It is completely legal for physicians to prescribe pharmaceutical drugs for off-label uses, so long as what they are doing is not “research” –Of course, off-label use of pharmaceutical drugs could potentially subject doctors to liability for malpractice.

May 13, 2005North Carolina State University Malpractice and Off-Label Prescriptions According to the law firm of Gary C. Johnson,Gary C. Johnson –“Using drugs in other ways than described in the FDA approved label is called ‘off-label’ use. We believe that innocent victims are entitled to justice to help rectify the wrong done to them.” –Also according to this same source, “Patients nationwide are being injured and killed from doctors prescribing drugs in ways that have not been certified by Food & Drug Administration (FDA) as effective and safe” –Clearly doctors have an incentive to protect themselves when they prescribe drugs for off-label uses.

May 13, 2005North Carolina State University Avoiding Malpractice for Off-Label Prescriptions According to several sources, physician’s can avoid malpractice claims in off-label prescriptions, that are not “research” if, –They ask themselves the following questions: Does the off-label use significantly increase risk to the patient? If the answer is “yes”, then the physician should inquire as to whether a reasonable number of physician’s are making off-label use of the drug? Only reliable source is peer-reviewed medical journals

May 13, 2005North Carolina State University Drug Manufacturers Have a huge stake in off-label uses of their products –One source estimates that 40 percent of the prescriptions are off-label40 percent of the prescriptions are off-label In general, drug manufacturers are not allowed by statute and the FDA to promote off-label uses for the products –Not allowed to advertise off-label uses –Not allowed to induce physicians to prescribe off-label uses

May 13, 2005North Carolina State University What Not to Do In June of 2004 it was reported that Pfizer agreed to pay more than $430 million in fines and civil judgmentsPfizer agreed to pay more than $430 million in fines –According to the FDA, the Parke-Davis Division of Warner Lambert (which was acquired by Pfizer in 2000) was aggressively marketing Neurontin for off- label uses Neurontin was approved for use as a supplemental anti- seizure epilepsy treatment –According to the DOJ, Warner-Lamber encouraged sales reps to provide unsolicited, one-on-one sales pitches to doctors about off-label uses of Neurontin Among the off-label uses were treatment of bipolar disorder, Lou Gerig’s disease, and ADD

May 13, 2005North Carolina State University What Not to Do Continuing –Warner-Lambert (WL)sales reps made false and misleading statements about what had been approved with respect to Neurontin –Apparently the WL sponsored “independent” medical education events The independence of these events was in question since WL was involved in speaker selection and the topics discussed WL paid consulting fees to physicians to attend consultant meetings in Hawaii and Florida at lavish resorts

May 13, 2005North Carolina State University On the other hand Abuses involving off-label uses of prescription drugs were apparently so common that Congress passed the Food and Drug Administration Modernization Act (FDAMA) of 1997Food and Drug Administration Modernization Act (FDAMA) of 1997 –Certainly there were other reasons for passage of the 1997 Act –Using this statute as authority, the FDA tried to enforce a rule that restricted circulation of academic journals to physicians by pharma companies This statement is subject to a number of exceptions

May 13, 2005North Carolina State University Free Speech In October of 1999, the FDA’s proposed rule was challenged in court –A federal district court ruled that the FDA’s rule violated the First Amendment rights of drug manufacturers –The court ruling enjoined the FDA from Prohibiting distribution by manufacturers to physicians of any article concerning prescription drugs published in a peer- reviewed professional journal and Enforcing other restrictions on distribution of medical education including content suggestions or speaker recommendation at independent medical education events

May 13, 2005North Carolina State University More Legalistic Stuff Like it or not, the medical sector is married to lawyers –Defining what is allowed and not allowed in off-label use and promotion is a much litigated issue –On the one hand, pharma firms apply to the FDA to get approval to market drugs for certain uses –Later, it becomes apparent that the drug has potential or actual other (off-label) uses –Again the stakes are enormous because of the percentage of off-label prescriptions

May 13, 2005North Carolina State University Post Launch Adverse Information Given the large amount of post-launch off-label prescriptions the FDA has set up a reporting site for adverse information – –At the Medwatch website, the FDA has an Adverse Event Reporting System (AERS) hyperlinkAERS –It is a much litigated as to how much adverse information is necessary for a recall The Vioxx case is illustrativeVioxx Reporting by pharma companies of adverse drug experiences to the FDA is quite complicated and the stakes are huge