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IOM recommendations on drug safety: relevance for vaccines? Bruce M Psaty, MD, PhD Cardiovascular Health Research Unit, Seattle, WA Drugs and vaccines: prevention Drugs Vaccines Payment Ad hoc VFC program Injury comp Tort law No-fault system Rx duration Long Short Rapid uptake DTCA Guidelines Phase III standard Surrogates Clinical benefit PM safety events Rare Uncommon Orenstein WA. Health Affairs 2005; 24: 599-610. CHRU US drug-safety system • Pharmaceutical industry lacks a symmetric interest in safety and efficacy • Since 1960s, approval marks transition from evaluation to marketing • With rapid approvals since 1992, current post-market system--AERS plus PM commitments--could hardly be weaker Steenburg C. Food Drug Law 2006; 61: 295-384. CHRU Guidance to assess safety • For new drugs intended for long-term use in non-life threatening conditions – 1500 subjects exposed – 300 to 600 subjects for 6 months – 100 subjects for 1 year • Rofecoxib NDA as example – 58 studies in 5771 patients – 3629 received rofecoxib 1 day or more – 752 received usual doses for 1 year Guidance ICH E1a, 1995. Villalba M. Review of Vioxx, 1999. CHRU US post-market safety system • FDA-based part of the system –AERS and some observational studies • Industry-based part of the system –PM commitments and other studies • 66% of med officers lack confidence that the “FDA adequately monitors the safety of prescription drugs … on the market” OIG Report. OEI-01-01-00590. March 2003. CHRU Post-market commitments • Agreed to by sponsors pre-approval • For one sponsor, 7 of 11 PMCs identified within 3 weeks of approval • Designed by sponsors, who often lack an imaginative interest in safety studies • Reviewed by OND medical officers, who often don’t know what studies to request OIG report. FDA review process, March 2003. CHRU Industry-funded studies • MEDAL program with 24,913 subjects –Compared etoricoxib and diclofenac –Similar pain relief, GI and CV AEs • Diclofenac as comparator –Best selling NSAID world-wide –COX2 selectivity similar to celecoxib –Compared with naproxen, 70% increase in vascular events Psaty BM. N Engl J Med 2007; 356: 328-30. CHRU Lifecycle approach • On-going evaluation of safety and efficacy of drugs during their market life • Systematic approach to identifying and translating safety signals into highquality studies • Pursuit and management of emerging knowledge about risks and benefits CHRU IOM recommendations • New funding, preferably from general revenues rather than user fees • New authorities for the FDA –Labeling and post-market studies –New enforcement tools • Black triangle and restricted direct to consumer advertising CHRU IOM recommendations • Leadership promoting a culture of safety • Access to new tools and new data • Integration of ODS/OSE in OND reviews and shared for post-market decisions • Development and use of risk-benefit analyses CHRU Some potential remedies • Congressional legislation –Clinical trials registration (S467) –Grassley-Dodd bill (S468) –Kennedy-Enzi bill (S484) –PUDFA reauthorization in 2007 • Wise drug use by physicians & patients –Suspend use of some drugs –Use well-studied drugs CHRU