1. FDA’s Role in the Risk Management of Opiate Analgesics Steven Galson, M.D., M.P.H. Deputy Center Director, Center for Drug Evaluation and Research Food and Drug Administration Bethesda, MD September 9, 2003

2. Risk Management for Drugs What is “Drug Safety”? The Food, Drug and Cosmetic Act: “Adequate tests by all methods reasonably applicable to show whether or not such drug is safe for use under such conditions”

3. What is “Drug Safety”? No drug is 100% “Safe” FDA Definition: Benefits outweigh foreseeable risks for: Specific Indication Specific Population

4. Predicting Risk Non-clinical studies Human data Incorporation of new science, when demonstrated to assist safety/efficacy evaluation

5. Predicting Risk: Human Data Premarket exposure: 2-10,000 people Varying duration & dosing Many concurrent illnesses Power to detect association for an event occurring 1 in 100 to 1 in 1000 people, depending on background rate No ability to quantitate rate of infrequent events

6. Predicting Benefit Randomized controlled trials Lack generalizability Often will not measure all domains Trials cannot predict uncertainties of use/abuse

7. In Approving a Product, FDA Determines that Product Benefit Exceeds Risks Benefit Inherent Risks

8. Drug is Approved: Poor Risk Management Profile Benefit Inherent Risks Errors Poor Prediction Abuse

9. Therefore, A Drug is Less “Safe” if: Used in a way that decreases foreseeable benefit Used in a way that increases the risk If the actual risks are greater than the predicted risk

10. FDA Goal – Managing Risk throughout product life cycle Beginning in drug review and approval process  Uses of multiple risk management tools- Label, restrictions, special requirements Continuing after approval  Passive surveillance, AERS  For opiates active systems, ie. DAWN  Special studies

11. FDA Role: Periodic evaluation of risks and benefits If: use changes, new risk/benefit data risk management not effective enough Then: Make changes consistent with statutes, regulations Enforcement of advertising regulations Coordinate with other federal agencies or other organizations

12. Special Case : Opiate Analgesics Safe and effective when used properly, but indications of increases in opiate related abuse and deaths Federal government regulatory authority & responsibility for risk management shared with DEA DEA responsible for enforcing regulations & laws designed to reduce abuse

13. FDA’s Challenges in Risk Management of Opiate Analgesics - 2003 Maintain positive risk-benefit balance Maintain access for patients who need these drugs Use label appropriately to foster risk management Science based decisions Current medical practice consensus Consider other risk management steps

14. Advisory Committee – Context Complex societal problem with multiple causes Complex problem=complex solution Regulation/public policy/education/research Addressing this problem is shared responsibility: regulatory agencies, SAMHSA, NIDA, state and local government, teachers, parents, NGOs, religious groups, etc.