Off-Label Use and Product Liability

							     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, 2005             North 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, 2005                 North 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, 2005         North Carolina State University
               Malpractice and Off-Label
                     Prescriptions
• According to the law firm of 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, 2005           North 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, 2005               North 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-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, 2005            North 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 judgments
     – 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, 2005                 North 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, 2005                North 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
  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, 2005                 North 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, 2005                 North 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, 2005           North 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
     – http://www.fda.gov/medwatch
     – At the Medwatch website, the FDA has an Adverse
       Event Reporting System (AERS) hyperlink
     – It is a much litigated as to how much adverse
       information is necessary for a recall
           • The Vioxx case is illustrative
           • Reporting by pharma companies of adverse drug
             experiences to the FDA is quite complicated and the stakes
             are huge


May 13, 2005                North Carolina State University