# Presentation: 364685

## IOM recommendations on drug safety:  relevance for vaccines?

- Bruce M Psaty, MD, PhD

## Drugs and vaccines: prevention

- 	Drugs	Vaccines

- Payment	Ad hoc	VFC program

- Rx duration	Long	Short

- Rapid uptake	DTCA	Guidelines

- Phase III standard	Surrogates	Clinical benefit

- PM safety events	Uncommon	Rare

- Injury comp	Tort law	No-fault system

- Orenstein WA.  Health Affairs 2005; 24:  599-610.

## 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.

## 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.

## 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.

## 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.

## 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.

## Lifecycle approach

- On-going evaluation of safety and efficacy of drugs during their market life
- Systematic approach to identifying and translating safety signals into high-quality studies
- Pursuit and management of emerging knowledge about risks and benefits

## 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

## 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

## 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