# Presentation: 228507

## Safety of VaccinesSome Principles

**Alastair J.J. Wood  M.D.**
**Managing Director**
**Symphony Capital LLC**

## Therapy and PreventionDifferences

**Therapy—person at risk of an AE is the person who derives benefit**
**Prevention—everyone at risk of an AE but only a few benefit**
**Therapy—we know who benefited and who had an AE**
**Prevention—we never know who benefited but we know who had an AE**

## Prevention vs. Therapy

**Therapy there is an ****individual**** risk/benefit ratio**
**Prevention there is no ****individual**** risk/benefit ratio **
**It is a ****population**** risk/benefit**
**Population risk/benefits change according to the population’s potential for benefit**
**But individual risk of an AE is constant**

## Vaccine SafetyDynamics of Population Safety/Benefit

**Knowledge of safety even more critical**
**Hard to have an ****individual**** risk/benefit discussion**
**Define population risk of disease**
**E.G. Smallpox—U.S. 2007 smallpox deaths?**
**Define population risk from vaccine**
**Population includes potential risk to others**
**Damage to public credibility of vaccines?**

## Vaccine Safety Post VioxxLessons Learned—Counterintuitive

**Types of adverse reactions—Rare in background population—liver failure**
**Reasonably easy to pick up an increase**
**Even a 4X increase—still small absolute numbers of cases**
**Common in background population—MI **
**Impossible to see in spontaneous reports**
**What does a “Viioxx MI” look like?**
**4X increase—massive public health impact**
**Hundreds of thousands injured!**

## Vaccine Safety Post VioxxLessons Learned

**Spontaneous reporting systems**
**Limited utility **
**Post marketing surveillance **
**Rare (in background)—potentially useful**
**Common (in background)—not likely useful**
**Need a comparison group**

## Vaccine Safety Post VioxxLessons Learned

**However for vaccines in children**
**Common morbidities do not occur**
**Thus the Vioxx lesson not as relevant**
**Rare events (in background) are risks**
**Spontaneous reporting systems potentially effective **
**No hypothesis for increase in “common events” of major morbidity/mortality importance**

## Vaccine Safety Post VioxxLessons Learned—Conflicts of Interest

**FDA does not promote drugs!**
**Yet concerns about independence of approval and safety**
**Independence of OSE **
**Reporting structure**
**Resources**
**Can FDA second guess itself?**
**CDC does promote vaccinations!**
**Can CDC second guess itself?**
**Will/should public be comfortable?**

## Vaccine Safety Post VioxxLessons Learned—Conflicts of Interest

**CDC does promote vaccination**
**If a problem occurs will public be comfortable with independence of judgments on safety/efficacy? **
**Need independent safety review**
**Clinical trial DSMBs may be a model**
**Appearance, independence and transparency is the issue**
**Reporting structure**

## Vaccine Safety

**Pre-marketing safety evaluation**
**Post marketing review**
**Regular at fixed frequencies?**
**Incidents?**
**Public review?**
**Use of data bases**
**Targeted studies**
**Hypothesis testing when appropriate**

## Vaccine Safety Who Should Do It?

**Functions of vaccine promotion and safety evaluation need to be separate**
**Need to be transparent and public**
**Free of politics**
**Should not reside in CDC**
**Should be free of political meddling**
**And seen to be**
**Should have an independent reporting structure **

## Vaccine SafetyWho Should Do It?

**Needs an independent home and review**
**IOM—Transparency?**
**Needs to maintain public confidence**
**Vaccines are critical to public health**
**Critical to maintain confidence in safety review**
**Critical that public trusts those who speak on vaccine safety**

## Vaccine Safety

**Maintaining the public’s trust is key**
**Ongoing and public review of safety**
**Clear action plans**
**Public discussion of risk/benefit **