# Presentation: 106734

## 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

## 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”**

## What is “Drug Safety”?

**No drug is 100% “Safe”**
**FDA Definition:  Benefits outweigh**
**	**** ****foreseeable risks for:**
**Specific Indication**
**Specific Population**

## Predicting Risk 

**Non-clinical studies**
**Human data**
**Incorporation of new science, when demonstrated to assist safety/efficacy evaluation**

## 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**

## Predicting Benefit

**Randomized controlled trials**
**Lack generalizability**
**Often will not measure all domains**
**Trials cannot predict uncertainties of use/abuse**

## In Approving a Product, FDA Determines that Product Benefit Exceeds Risks

**Benefit**

**Inherent Risks**

## Drug is Approved:  Poor Risk Management Profile

**Benefit**

**Inherent Risks**

**Errors**

**Poor Prediction**

**Abuse**

## 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**

## 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**

## 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**

## 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**

## 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**

## 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.**