Virendra Kumar


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OFF-LABEL MARKETING OF PHARMACEUTICALS PRODUCTS - This is my first credit seminar presentation over off label promotion of pharmaceutical products.
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Virendra Kumar

  1. 1. INDICATION : ERECTILE DYSFUNCTION off-label marketing
  2. 2. INDICATION : HYPERTENSION off-label marketing
  3. 3. DOES THIS SOUND ABSURD ??? off-label marketing
  5. 5. <ul><li>Off-label use </li></ul><ul><li>Off-label marketing </li></ul><ul><li>Off-label prescription </li></ul><ul><li>Off-label promotion </li></ul><ul><li>Case studies </li></ul><ul><li>Drugs commonly used off label </li></ul><ul><li>FDAMA-1997 </li></ul><ul><li>Concluding remarks </li></ul>off-label marketing
  6. 6. <ul><li>The FDA regulates the manufacture, labeling, and promotion of drugs </li></ul><ul><ul><li>In the NDA, the applicant has to prove that the drug is safe and effective for various uses </li></ul></ul><ul><ul><ul><li>These uses become the labeled uses…the uses for which the tests have been conducted. </li></ul></ul></ul><ul><ul><ul><li>Once a drug is approved by the FDA, various medical researchers and practictioners may discover that such drugs have other valid (off-label) uses. </li></ul></ul></ul>off-label marketing
  7. 7. <ul><ul><li>The FDA does not regulate the practice of medicine </li></ul></ul><ul><ul><li>It is completely legal for physicians to prescribe pharmaceutical drugs for off-label uses, so long as what they are doing is not “research” </li></ul></ul><ul><ul><li>off-label use of pharmaceutical drugs could potentially subject doctors to liability for malpractice. </li></ul></ul>off-label marketing
  8. 8. <ul><li>Off-label prescription </li></ul><ul><li>FDA regulations pro hibit DTC promotion & restrict physician–targeted promotion </li></ul><ul><li>Unproven off-label use may be costly and threaten patient safety </li></ul>off-label marketing
  9. 9. <ul><li>FDA </li></ul><ul><ul><li>focuses on market entry </li></ul></ul><ul><ul><li>historically maintained a ‘hands-off’ approach </li></ul></ul><ul><li>Sometimes little market incentive to seek approval for additional indications: </li></ul><ul><ul><li>older & generically available drugs </li></ul></ul><ul><ul><li>population size too small </li></ul></ul><ul><li>No alternatives exist: orphan drugs & pediatric </li></ul><ul><li>Desire to broaden therapeutic alternatives: </li></ul><ul><ul><li>failure of standard therapy </li></ul></ul><ul><ul><li>innovation seeking behavior </li></ul></ul>off-label marketing
  10. 10. <ul><li>Have a huge stake in off-label uses of their products </li></ul><ul><ul><li>One source estimates that 40 percent of the prescriptions are off-label </li></ul></ul><ul><li>In general, drug manufacturers are not allowed by statute and the FDA to promote off-label uses for the products </li></ul><ul><ul><li>Not allowed to advertise off-label uses </li></ul></ul><ul><ul><li>Not allowed to induce physicians to prescribe off-label uses </li></ul></ul>off-label marketing
  11. 11. <ul><li>Clinically Reasonable </li></ul><ul><li>Well-known evidence based-therapy </li></ul><ul><li>Supported by treatment guidelines </li></ul><ul><li>Other drugs in class are indicated </li></ul><ul><li>Cost-effective generic substitution </li></ul><ul><li>Innovative approaches when standard therapies fail </li></ul><ul><li>Concerns </li></ul><ul><li>May not bear same degree of clinical or scientific scrutiny as labeled indications </li></ul><ul><li>Inconclusive evidence: </li></ul><ul><ul><li>contraindications </li></ul></ul><ul><ul><li>safe dose </li></ul></ul><ul><ul><li>ADRs </li></ul></ul><ul><li>Over use of unproven off-label therapies may be costly </li></ul>off-label marketing
  12. 12. <ul><li>In general, doctors may prescribe a drug for unapproved uses </li></ul><ul><li>In general, manufacturers may not promote unapproved uses. </li></ul><ul><li>Benefits: some off-label uses are scientifically valid and provide tremendous benefits to patients, especially in areas of life-saving drugs </li></ul><ul><li>Risks: no guarantee of scientific validity; unknown health risks; waste of public resources; certain side effects not justified </li></ul>off-label marketing
  13. 13. <ul><li>Profit motive: </li></ul><ul><li>-Clinical trials costly </li></ul><ul><li> -Off-label sales can be significant </li></ul><ul><li>-These factors can affect corporate judgment </li></ul><ul><li>Off-label promotion relies on covert marketing techniques </li></ul><ul><li>Before 1997, FDA allowed dissemination of information about off-label uses only when such information was solicited by the physician </li></ul>off-label marketing
  14. 14. off-label marketing Figure 1. Proportion of Off-Label Prescribing by Functional Class
  15. 15. off-label marketing
  16. 16. <ul><li>In June 2004,Pfizer had paid $ 430 in fine and civil judgments </li></ul><ul><li>Acc. To FDA ,the Parke – Davis division of Warner Lambert (which was acquired by Pfizer in 2000) was aggressively marketing Neurontin for off-label uses. </li></ul>off-label marketing
  17. 17. <ul><li>Neurontin® (gabapentin) is indicated as adjunctive therapy in the treatment of partial seizures with and without secondary generalization in adults with epilepsy, at doses ranging between 900 mg to 1800 mg per day </li></ul>off-label marketing APPROVED INDICATION (between 1994 – 2001)
  18. 18. <ul><li>Alcohol Detoxification </li></ul><ul><li>Amyotrophic Lateral Sclerosis </li></ul><ul><li>Antidepressant-Induced Bruxism </li></ul><ul><li>Anxiety Disorder; Panic Disorder; OCD </li></ul><ul><li>Behavior Problems - Dementia-Related </li></ul><ul><li>Bipolar Disorder; Mania </li></ul><ul><li>Borderline Personality Disorder </li></ul><ul><li>Brachioradial Pruritus </li></ul><ul><li>Central Nervous System Disorders </li></ul><ul><li>Charles Bonnet Syndrome </li></ul><ul><li>Cluster Headache </li></ul><ul><li>Cocaine Dependency </li></ul><ul><li>Dystonia </li></ul><ul><li>Essential Tremor </li></ul><ul><li>Headache (SUNCT) </li></ul><ul><li>Migraine Prophylaxis </li></ul><ul><li>Multiple Sclerosis Complications </li></ul><ul><li>Myalgias - Taxane Induced </li></ul><ul><li>Neuropathic Cancer Pain </li></ul><ul><li>Neuropathic Pain Syndromes </li></ul><ul><li>Neuropathy - HIV-Related </li></ul><ul><li>Nicotine Withdrawal </li></ul><ul><li>Nystagmus </li></ul><ul><li>Orthostatic Tremor </li></ul><ul><li>Pain - Postpoliomyelitis Pain </li></ul><ul><li>Pain - Reflex Sympathetic Dystrophy </li></ul><ul><li>Partial Seizures - Monotherapy </li></ul><ul><li>Phantom Limb Syndrome </li></ul><ul><li>Restless Legs Syndrome </li></ul><ul><li>Social Phobia </li></ul><ul><li>Spasticity </li></ul>off-label marketing
  19. 19. off-label marketing
  20. 20. <ul><li>Voicemail recordings </li></ul><ul><li>Internal documents </li></ul><ul><li>Vendor documents </li></ul><ul><li>Data (IMS, Scott-Levin, Verispan, Medicaid) </li></ul><ul><li>Witnesses (Sales people, doctors) </li></ul><ul><li>Patent applications </li></ul>off-label marketing
  21. 21. <ul><li>Medical Liaisons </li></ul><ul><li>Consultant and advisory board meetings </li></ul><ul><li>CMEs </li></ul><ul><li>Dinner meetings and teleconferences </li></ul><ul><li>Preceptorships </li></ul>off-label marketing
  22. 22. <ul><li>Payments to physicians (~$ 50 million to 3,000 physicians) </li></ul><ul><li>-Grants </li></ul><ul><li>-Speaker fees </li></ul><ul><li>-Honoraria </li></ul><ul><li>-Paid vacations </li></ul><ul><li>-Olympics tickets </li></ul><ul><li>Ghostwritten articles </li></ul><ul><li>Suppress negative information </li></ul>off-label marketing
  23. 23. <ul><li>US Patent 5,084,479: “Neuro-degenerative diseases” (1990) </li></ul><ul><li>US Patent 5,510,381: “mania and bipolar disorder” (1995) </li></ul><ul><li>US Patent 5,792,796: “anxiety and panic” (1995) </li></ul><ul><li>US Patent 6,242,488: “pain” (2000) </li></ul><ul><li>US Patent 6,426,368: “alcoholism” (2001) </li></ul>off-label marketing
  24. 24. <ul><li>Initial estimate for lifetime sales of Neurontin was $500 million </li></ul><ul><li>Off-label marketing was successful: in 2003 use of Neurontin for unapproved uses accounted for nearly 90% of its sales </li></ul><ul><li>Sales of Neurontin now exceed $2 billion annually </li></ul>off-label marketing
  25. 25. off-label marketing PAIN (NEURONTIN V. DILANTIN)
  26. 26. <ul><li>Warner-Lambert pled guilty to two counts of violating the Food Drug & Cosmetic Act </li></ul><ul><li>Warner-Lambert paid $430 million: </li></ul><ul><li>-$152 million to settle federal civil False Claims Act liabilities </li></ul><ul><li>-$38 million to settle its state civil liabilities to the fifty sates and fund remediation program </li></ul><ul><li>-$240 million federal criminal fine </li></ul>off-label marketing
  27. 27. <ul><li>Approximately 40% of all drug use is off-label </li></ul><ul><li>33% of all prescriptions in cancer treatment </li></ul><ul><li>81% of patients with AIDS receive at least one drug off-label </li></ul><ul><li>56% of all prescriptions for antidepressants </li></ul><ul><li>Nearly all pediatric patients are prescribed drugs off-label </li></ul><ul><li>Source: Tabarrok, 2000 </li></ul>off-label marketing
  28. 28. <ul><li>Otsuka American Pharmaceutical, the US unit of the Japanese drugmaker, agreed to pay more than $4 million to resolve allegations that it marketed the Abilify antipsychotic for off-label uses, according to the US Department of Justice . </li></ul><ul><li>From 2002 through 2005, Otsuka knowingly promoted the sale and use of Abilify for pediatric use and to treat dementia-related psychosis, although at the time, the FDA had not approved the drug for use in geriatric patients, teenagers or children. </li></ul>Pharma Blog - 2008 March 27 CASE-2 se – 2
  29. 29. <ul><li>Botox example </li></ul><ul><ul><li>1989: FDA approved for facial neurological movement disorders </li></ul></ul><ul><ul><li>2002: FDA approved to combat wrinkles and excessive underarm sweating </li></ul></ul><ul><ul><li>Currently, FDA approved for both </li></ul></ul><ul><ul><li>cosmetic and therapeutic uses </li></ul></ul><ul><li>Until 2002, it wasn’t illegal from FDA to use Botox for wrinkles but it was prohibited to advertise it for wrinkles </li></ul>off-label marketing
  30. 30. <ul><li>ASPIRIN (used off- label till 1998,to reduce the risk of heart attack) </li></ul><ul><li>Viagra (off-label use for erectile dysfunction) </li></ul><ul><li>Minoxidil (used off-label for hair growth) </li></ul>off-label marketing
  31. 31. <ul><li>GABAPENTIN (anticonvulsant) </li></ul><ul><li>83%: 20% supp. / 80% no supp. </li></ul><ul><li>AMITRIPTYLINE (psychiatric:tri-cyclic antidepressant) 79%: 25% supp. / 75% no supp. </li></ul><ul><li>ISOSORBIDE MONONITRATE (cardiac: nitrate) </li></ul><ul><li>75%: 64% supp. / 36% no supp. </li></ul><ul><li>DIGOXIN (cardiac: dysrythmia) </li></ul><ul><li>66%: 38% supp. / 62% no supp. </li></ul><ul><li>RISPERIDONE (psychiatric: anti-psychotic) </li></ul><ul><li> 66%: 1% supp. / 99+% no supp. </li></ul>off-label marketing
  32. 32. <ul><li>ACTIQ – By Cephalon, oral tarnsmucosal fentanyl citrate(OTFC) is used off-label to treat moderate to severe chronic, non-malignant pain even though it is FDA-approved solely for break-through pain in cancer patients. </li></ul><ul><li>Bevacizumab (Avastin, Genentech/Roche) is a monoclonal antibody against vascular endothelial growth factor (VEGF). has been used against Age Related Macular Degeneration, but the evidence for its use is anecdotal. </li></ul>off-label marketing
  33. 33. <ul><li>Carbamazepine , or Tegretol, has been used as a mood stabilizer and is accepted treatment for bipolar disorder . </li></ul><ul><li>Methotrexate (MTX), approved for the treatment of choriocarcinoma, is frequently used for the medical treatment of an unruptured ectopic pregnancy. There is no FDA-approved drug for this purpose and there is little incentive to sponsor an unpatented drug such as MTX for FDA-approval. </li></ul>off-label marketing
  34. 34. <ul><li>In 1997, Congress passed FDAMA allowing manufacturers to disseminate information about off-label uses to health care providers under certain circumstances </li></ul><ul><li>FDAMA purports to liberalize the dissemination of information regarding off-label use to health care professionals, but the requirements for legally disseminating such information are burdensome </li></ul>off-label marketing
  35. 35. <ul><li>Off-label marketing had benefited in past by unveil the unknown uses of drugs ,but at the same time ,case like Neurontin ® etc..shows that it has detrimental effect on people who were victims of Off-label marketing. </li></ul><ul><li>Physicians need to understand their responsibility </li></ul><ul><li>Current Indian scenario is totally different </li></ul>off-label marketing
  36. 36. off-label marketing