Table 2

Use of risk assessment framework in assessing tobacco harm reduction

Hazard identification Dose response Exposure assessment Risk characterisation Risk management
Information required as described in 1983 “Red Book” Epidemiology; animal bioassay; short term studies; comparisons of molecular structureEpidemiology; low dose extrapolation; animal to human extrapolationDose to which humans are exposed; dose of special populations; estimation of size of population potentially exposedEstimate of the magnitude of the public health problemA risk assessment (qualitative or quantitative) may be one of the bases of risk management
Challenges in risk assessment of conventional tobacco products Complex mixture; animal models are limited; constituents and additives are proprietary informationDose changes for an individual over time; dose of individual toxicants varies over time; exposure at time of disease progressionChanges in smoking topography; complex mixtureFor which disease? At which point in smoking history?FTC regarding advertising
Additional challenges of PREP risk assessment Tobacco related products will change rapidly with timeAssessing effect of moving backwards on a dose exposure curve, assuming long time previous higher exposureChanging exposure after long term higher dose exposure; some toxicants could increaseNeed models to consider effects on initiation, cessation, and relapseFDA authority currently exerted only over pharmaceutical PREPs
Committee charge 1. Does product decrease exposure to theharmful substances in or produced during use of tobacco?2. Is decreased exposure associated with decreased harm to health? 3. Are there useful surrogate indicators of disease that could be used?1. Does product decrease exposure?4. What are the public health implications?4. What are the public health implications?
Disease specific summary data (chapter 5; section II) 3.Utility of preclinical research to judge feasibility 1.Dose–response data for conventional tobacco products
2.Validation and development of biomarkers 4.Short term clinical and epidemiological studies
2.Validation and development of biomarkers 4.Short term clinical and epidemiological studies5. Long term epidemiological studies and surveillance
Principal conclusions 1. Risk reduction is feasible
4. Exposure reduction can be demonstrated
3. Surrogate measures could be used to predict risk reduction4. Exposure reduction can be demonstrated1. Risk reduction is feasible
2. Risk reduction not yet demonstrated
6. Public health impact is unknown
5. Regulation is a necessary precondtion for asuring a science base and for assuring protection of the health of the public
Elements of surveillance system Specific tobacco constituents of both the products and the smoke they generateDisease outcomesConsumption of tobacco products and of PREPs; biomarkers of exposure to tobacco products; personal tobacco product use and related behavioural patterns Disease outcomes Tobacco product marketing, including PREPs
Regulatory principles (all refer to tobacco related PREPS, except for 11) 1. Ingredient disclosure
3. Preclinical testing required to support health related claims
7. Evidence for no increased risk
8. Added ingredient review
9. Performance standards
6. Products with claims would require postmarketing surveillance and epidemiological studies2. Yield assessment
4. With specific claims, no increased exposure to unclaimed compounds
9. Performance standards
11. Exposure reduction claims for pharmaceutical PREPs
5.Labelling for products with claims cannot be false or misleading10. Enforcement power
Recommendations 3. Develop appropriate animal models and in vitro assays of pathogenesis1. Sufficient data to allow estimation of D-R
2. Need to develop validated biomarkers of disease
4. Clinical and epidemiological studies in human are required Comprehensive surveillance is recommendedRegulation is recommended