1. Presenting Truthful Information to Doctors Aaron S. Kesselheim, M.D., J.D. Brigham and Women ’ s Hospital Harvard School of Public Health Boston, Massachusetts National State Attorney General Program at Columbia Law School May 11, 2007 akesselheim@partners.org

2. Today ’ s Agenda I. How physicians learn about drug products I. How physicians learn about drug products II. How litigation influences the information available and the way it is communicated II. How litigation influences the information available and the way it is communicated III. Ways to continue to promote dissemination of accurate information to prescribers III. Ways to continue to promote dissemination of accurate information to prescribers

3. Presenting Information to Physicians Commercial sources Commercial sources Advertisements Advertisements Manufacturer-funded CME Manufacturer-funded CME Detailers Detailers Strong, consistent, specific, and independent association between physicians ’ behaviors and their exposure to detailers Strong, consistent, specific, and independent association between physicians ’ behaviors and their exposure to detailers

4. Presenting Information to Physicians Deficiencies in information presented Deficiencies in information presented Withheld as trade secret Withheld as trade secret Ex: duloxetine for urinary incontinence Ex: duloxetine for urinary incontinence Presenting to the FDA fulfills manufacturer duty Presenting to the FDA fulfills manufacturer duty Ex: cerivastatin rhabdomyolysis side effect Ex: cerivastatin rhabdomyolysis side effect Protracted negotiations regarding label wording Protracted negotiations regarding label wording Ex: cisapride and five-year delay Ex: cisapride and five-year delay Obscure truth in promotion to physicians Obscure truth in promotion to physicians Ex: rofecoxib and cardiovascular risks Ex: rofecoxib and cardiovascular risks Inaccurate Inaccurate

5. The Role of Litigation Improve quality of information about drug risks Improve quality of information about drug risks 1. Uncover important and previously unavailable data 1. Uncover important and previously unavailable data Lead to reassessment of drug products Lead to reassessment of drug products Ex.: paroxetine and suicidality Ex.: paroxetine and suicidality

6. The Role of Litigation 2. Reveal manufacturer policies regarding presenting information to physicians 2. Reveal manufacturer policies regarding presenting information to physicians Delays in revealing data, attempts to minimize severity Delays in revealing data, attempts to minimize severity Improper marketing practices Improper marketing practices Ex.: Serostim, Neurontin litigation Ex.: Serostim, Neurontin litigation Misrepresenting price information Misrepresenting price information Ex.: AWP litigation Ex.: AWP litigation

7. The Role of Litigation 3. Shed light on deficiencies in US regulatory process 3. Shed light on deficiencies in US regulatory process Change FDA ’ s official position on specific drug products Change FDA ’ s official position on specific drug products Ex.: paroxetine and withdrawal side effects Ex.: paroxetine and withdrawal side effects Expose limitations in FDA information collection and dissemination procedures Expose limitations in FDA information collection and dissemination procedures Ex.: cerivastatin and reporting side effects Ex.: cerivastatin and reporting side effects

8. Promoting Dissemination of Accurate Information to Prescribers Numerous systems aimed to promote rational use of drugs Numerous systems aimed to promote rational use of drugs Ex. #1: Independent Drug Information Service Ex. #1: Independent Drug Information Service

9. Balanced data about medications www.RxFacts.org

10. Promoting Dissemination of Accurate Information to Prescribers Optimize medication therapy Optimize medication therapy Can involve educating about generic alternatives Can involve educating about generic alternatives Educational materials provide clinical and cost data Educational materials provide clinical and cost data Goal: Lower cost by providing better medicine. Goal: Lower cost by providing better medicine. Emphasis on quality of care, not just cost

11. Promoting Dissemination of Accurate Information to Prescribers Materials prepared by clinicians at Harvard Medical School Materials prepared by clinicians at Harvard Medical School Evidence documents – review all recent literature Evidence documents – review all recent literature “ Un-advertisements ” “ Un-advertisements ” Patient scenarios Patient scenarios Physician reference cards Physician reference cards Patient education materials – help facilitate prescribing change Patient education materials – help facilitate prescribing change

12. Promoting Dissemination of Accurate Information to Prescribers Ex. #2: Using monetary recovery from Neurontin litigation to educate physicians Ex. #2: Using monetary recovery from Neurontin litigation to educate physicians Provide clinicians with basic tools for: Provide clinicians with basic tools for: Weighing drug data Weighing drug data Immunizing practitioners from problematic aspects of drug marketing Immunizing practitioners from problematic aspects of drug marketing Providing greater understanding of drug development and approval process Providing greater understanding of drug development and approval process

13. Promoting Dissemination of Accurate Information to Prescribers Preemption Preemption Jan 2006: FDA inserted into comment made on discussion of largely unrelated federal regulation Jan 2006: FDA inserted into comment made on discussion of largely unrelated federal regulation Would absolve mfrs of adequately evaluating or reporting risks associated with their products Would absolve mfrs of adequately evaluating or reporting risks associated with their products Four courts have used this comment to hold litigation preempted by FDA approval Four courts have used this comment to hold litigation preempted by FDA approval The issue: whether state AGs may be deprived of jurisdiction over the adequacy of messages transmitted to consumers within their borders by pharmaceutical manufacturers The issue: whether state AGs may be deprived of jurisdiction over the adequacy of messages transmitted to consumers within their borders by pharmaceutical manufacturers

14. FDA Approval is Just The Beginning Manufacturers ’ message to physicians can overstate the benefits and understate the risks of approved products Manufacturers ’ message to physicians can overstate the benefits and understate the risks of approved products Attorney General investigations: Attorney General investigations: Promote disclosure of information Promote disclosure of information Promote appropriate manufacturer behavior Promote appropriate manufacturer behavior Promote better understanding among physicians of how messages can affect their prescribing practices Promote better understanding among physicians of how messages can affect their prescribing practices

15. Thanks to… Thanks to… Jerry Avorn, M.D. Jerry Avorn, M.D. Michelle Mello, J.D., Ph.D. Michelle Mello, J.D., Ph.D.