Drug Safety After Vioxx

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

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. Thank you! Daniel E. Troy Sidley Austin Brown and Wood 202-736-8304 Dtroy@sidley.com