1. Drug Safety After Vioxx
Daniel E. Troy

2. The Situation Before 2004 healthy appreciation for risk benefit
all drugs have risks
FDA as a risk management agency
lessons of the AIDs experience
Bayesian statistics discussion
Focus on post-marketing systems
role of PDUFA
March 2003 – SADER rule – to reduce signal to noise ratio
Also, working on reducing signal to noise ratio of info dumped on IRBs
Paul Seligman – said FDA moving away from considering AERs as FDA’s only tool in postmarketing arena FDA will be “using that system as just one of a series of tools in trying to identify problems in the post-marketing environment.” Understood “inherent limitations” of the postmarketing reporting system.

3. 2004
Flu Vaccine
SSRIs
Vioxx

4. Consequences Pendulum has swung dramatically Slow-down in approvals
Increased requests for pre-market studies
Routine use of black box warnings
Routine use of RiskMAPs
Tysabri “pause”
Palladone withdrawal

5. Vioxx verdict Sanford Bernstein analysis
Apparently tried Baycol approach, but need to win
$235 million, will be reduced to $26.1 million
But times 4000, 40,000, 140,000?
Reflects that new regulators are
plaintiffs’ lawyers and state juries
state AG’s
US Attorneys
None of whom are scientific

6. Consequences of over-caution due to products liability situation
Bendectin
Norplant
Lack of research, esp. in women’s health
Focus on therapies for cancer and other serious diseases rather than on therapies for the broader population

7. FDA Regulatory Responses
RiskMaps
Drug Safety Board
“Drug Watch”

8. RiskMaps May 2004 – availability of 3 risk management guidances
Becoming routine, and ever-more restrictiveProblem – due, some say, to Rezulin, FDA seems to have lost its confidence in its risk-management tools
But statute is red-light\green-light
Specific risk management tools
prescription status
labeling
Dear doctor letters
imminent hazard authorities
withdrawal
Routine and restrictive riskmaps also undermine practice of medicine and pharmacists policy

9. Caselaw on RiskMAPs Methadone case McNeilab v. Heckler
“FDA has no right to put manufacturer’s to the Hobson’s choice of either accepting recommendations for actions which the agency could not require, or facing rejection of their NDAs.”

10. Other issues raised by RiskMAP guidances
State that CDER and CBER will develop internal policies and procedures regarding review of Riskmaps, identifying “milestone points at which RiskMAP discussion is logical”
This degree of regularization requires rulemaking
GE v. EPA and other cases
generally watch for FDA evasion of rulemaking process through use of guidance

11. Drug Safety Oversight Board
Disassociates benefits from risks
Incentives

12. Drug Watch – “Emerging” Risk Information
If implemented, needs to be done through rulemaking
Inconsistent with Data Quality Act and Peer Review Bulletin
At odds with function of FDA – to speak authoritatively
At odds with structure of FDCA, which lays out certain risk management tools, e.g., labeling.
Tension with section 705
“imminent danger to health or gross deception of the consumer”

13. Drug Watch – Some policy issues
Not clear what the threshold is for posting information
Create confusion with prescribers and patients
Increase product liability exposure
No clear provisions for updating\removing information
No advance notice to companies, which have the expertise
Focuses on risks only

14. A few suggestions Data mining Partnerships with health care providers
PV audits
Putting patients first – REALLY.

15. Sidley Austin Brown and Wood
Thank you!
Daniel E. Troy
Sidley Austin Brown and Wood