Drug Safety After Vioxx Daniel E. Troy

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.

2004 Flu Vaccine SSRIs Vioxx

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

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

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

FDA Regulatory Responses RiskMaps Drug Safety Board “Drug Watch”

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

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.”

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

Drug Safety Oversight Board Disassociates benefits from risks Incentives

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”

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

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

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