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 structure | Epidemiology; low dose extrapolation; animal to human extrapolation | Dose to which humans are exposed; dose of special populations; estimation of size of population potentially exposed | Estimate of the magnitude of the public health problem | A 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 information | Dose changes for an individual over time; dose of individual toxicants varies over time; exposure at time of disease progression | Changes in smoking topography; complex mixture | For which disease? At which point in smoking history? | FTC regarding advertising |
| Additional challenges of PREP risk assessment | Tobacco related products will change rapidly with time | Assessing effect of moving backwards on a dose exposure curve, assuming long time previous higher exposure | Changing exposure after long term higher dose exposure; some toxicants could increase | Need models to consider effects on initiation, cessation, and relapse | FDA 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 studies | 5. 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 reduction | 4. Exposure reduction can be demonstrated | 1. 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 generate | Disease outcomes | Consumption 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 studies | 2. 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 misleading | 10. Enforcement power |
| Recommendations | 3. Develop appropriate animal models and in vitro assays of pathogenesis | 1. 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 recommended | Regulation is recommended |