The APPH Standard: What Does it Actually Mean?

My presentation at the Food & Drug Law Institute Tobacco and Nicotine conference 26 October 2023. I discuss five problems with the APPH concept:
1. No means of trading off different types of benefits and detriments
2. Ignores vaping benefits to youth
3. Blind to harmful unintended consequences of marketing denial orders
4. Impossible to estimate population effects at the product level - the standard only makes sense at the category level.
5. The aggregate effect of thousands of single product PMTA determinations may create adverse effects not captured in any individual application (de fact flavour ban)

I finish with three broad proposals:
1. Assess individual risk and marketing strategy pre-market
2. Assess population effects when it is actually possible to observe them - post-market
3. Conduct a single comprehensive market assessment covering all products, including illicit trade

1. Food and Drug Law Institute Tobacco and Nicotine Products Regulation and Policy Conference Clive Bates, MA MSc The Appropriate for the Protection of Public Health (APPH) Standard: What Does it Actually Mean? 26-27 October 2023 Washington DC

2. Short text that doesn’t explain all that much What does APPH mean? Section 910 of the Federal Food, Drug, and Cosmetic Act - Application for Review of Certain Tobacco Products c.4. Basis for Finding.  For purposes of this section, the finding as to whether the marketing of a tobacco product for which an application has been submitted is appropriate for the protection of the public health shall be determined with respect to the risks and benefits to the population as a whole, including users and non-users of the tobacco product, and taking into account: A. the increased or decreased likelihood that existing users of tobacco products will stop using such products; and   B. the increased or decreased likelihood that those who do not use tobacco products will start using such products.

3. What does APPH mean? Section 910 of the Federal Food, Drug, and Cosmetic Act - Application for Review of Certain Tobacco Products c.4. Basis for Finding.   For purposes of this section, the finding as to whether the marketing of a tobacco product for which an application has been submitted is appropriate for the protection of the public health shall be determined with respect to the risks and benefits to the population as a whole, including users and non-users of the tobacco product, and taking into account: A. the increased or decreased likelihood that existing users of tobacco products will stop using such products; and   B. the increased or decreased likelihood that those who do not use tobacco products will start using such products. TCA establishes a decision-making standard.

4. What does APPH mean? Section 910 of the Federal Food, Drug, and Cosmetic Act - Application for Review of Certain Tobacco Products c.4. Basis for Finding.  For purposes of this section, the finding as to whether the marketing of a tobacco product for which an application has been submitted is appropriate for the protection of the public health shall be determined with respect to the risks and benefits to the population as a whole, including users and non-users of the tobacco product, and taking into account: A. the increased or decreased likelihood that existing users of tobacco products will stop using such products; and   B. the increased or decreased likelihood that those who do not use tobacco products will start using such products. Comparison of risks and benefits arising from marketing a new tobacco product

5. What does APPH mean? Section 910 of the Federal Food, Drug, and Cosmetic Act - Application for Review of Certain Tobacco Products c.4. Basis for Finding.  For purposes of this section, the finding as to whether the marketing of a tobacco product for which an application has been submitted is appropriate for the protection of the public health shall be determined with respect to the risks and benefits to the population as a whole, including users and non-users of the tobacco product, and taking into account: A. the increased or decreased likelihood that existing users of tobacco products will stop using such products; and   B. the increased or decreased likelihood that those who do not use tobacco products will start using such products. Covers whole population. Does not differentiate.

6. What does APPH mean? Section 910 of the Federal Food, Drug, and Cosmetic Act - Application for Review of Certain Tobacco Products c.4. Basis for Finding.  For purposes of this section, the finding as to whether the marketing of a tobacco product for which an application has been submitted is appropriate for the protection of the public health shall be determined with respect to the risks and benefits to the population as a whole, including users and non-users of the tobacco product, and taking into account: A. the increased or decreased likelihood that existing users of tobacco products will stop using such products; and   B. the increased or decreased likelihood that those who do not use tobacco products will start using such products. Considering all behaviour change triggered by the product introduction

7. Visualising the APPH language Risks Benefits Adolescents Adults Non-users Users

8. Visualising APPH – authorizing a vaping product Risks Benefits Adolescents Adults Uptake of vaping by adolescents who would otherwise never use nicotine. Health effects? Dependence? Gateway? Uptake by never-smokers or former smokers Displaces abstinence? Progress to smoking? Dependence? Switching from cigarettes Diversion from smoking uptake Smoking cessation or reduction, better health & wellbeing Financial savings Hedonistic, functional, therapeutic benefits of nicotine

9. Problem 1: no basis for trade-offs Risks Benefits Adolescents Adults Uptake of vaping by adolescents who would otherwise never use nicotine. Health effects? Dependence? Gateway? Smoking cessation or reduction, better health & wellbeing Financial savings Overwhelming emphasis on youth – but these risks are minor and transient, though politically salient No way of trading off substantial adult benefits with qualitatively different youth harms

10. Illustrative questions How to compare different risks (e.g., ‘addiction’ vs. cancer) arising at different times and to make trade-offs? What is the ‘exchange rate’ between net extra teen vaping and adult smoking cessation?

11. FDA uses QALYs in its deeming rule analysis

12. 1.0 0.0 Quality of life Years of life from now QALYs: How to trade risks and benefits 1.0 0.0 Quality of life Years of life from now Decline Death

13. Discounting – far off QALYs are worth less 1.0 0.0 Quality of life Years of life from now Discounting at 3% Using established concepts of health economics would drive FDA to focus on maximising adult smoking cessation

14. Problem 2: Ignoring vaping benefits to youth Risks Benefits Adolescents Adults Switching from cigarettes Diversion from smoking uptake Youth benefits may be significant, but ruled inadmissible by FDA and impossible for applicants to show “…the increased or decreased likelihood that those who do not use tobacco products will start using such products.”

15. Problem 2: How to reflect vaping benefits to youth?

16. Illustrative questions On what basis can FDA ignore significant vaping benefits to some adolescents? Is it even possible for individual applicants to make this argument?

17. Marketing Granted Order Without decision After decision Granted (MGO) Expected behaviour change Change

18. Marketing Denial Order Denied (MDO) Change Without decision After decision Products withdrawn

19. Problem 3: unintended consequences Denied (MDO) Behavioural response Increased smoking Illicit trade Disposables Youth engaged in illicit supply User workarounds Supplier innovation Not assessed Without decision After decision

20. Illustrative questions When the FDA denied the Juul PMTA, who cared about the welfare of three million Juul users? How does FDA factor in the real-world rise of illicit vape products?

21. Problem 4: product versus category Rest of the market New product APPH only makes sense for large-scale segments of the market – otherwise users just substitute FDA de facto operates a category approach in its evidence standard for flavoured ENDS

22. Illustrative questions How can one product affect population health when users can switch to a similar product? How can APPH be assessed other than for whole categories or dominant products?

23. Problem 5: aggregate effects of multiple PMTA determinations Six ENDS systems < 3% market All tobacco flavour All closed systems All tobacco owned Several obsolete 26.3 million applied 99.9999% rejected

24. Problem 5: aggregate effects – a de facto flavour ban …we find a tradeoff of 15 additional cigarettes for every 1 less 0.7 mL ENDS pod sold due to ENDS flavor restrictions. …. cigarette sales increase even among brands disproportionately used by underage youth . ….any public health benefits of reducing ENDS use via flavor restrictions may be offset by public health costs from increased cigarette sales.

25. Illustrative questions How can the aggregate effects of thousands of similar decisions be captured in individual applications? Do FDA’s PMTA assessments – when aggregated – function as de facto standards (e.g., flavour ban, open systems ban)?

26. Three possible solutions Address individual risks at the product level with pre-market assessment Pre-market focus on individual risk and safety (chemical, electrical, thermal, etc) Pre-market assessment of marketing and youth appeal (packaging etc) Adopt soft standards (“comply or justify”) in guidance and S.907 hard standards where appropriate Address population risks at the category level with post-market correctives Post-market monitoring and retrospective action for adverse population effects Use discounted QALYs to inform analysis – focus attention on smoking cessation Recognise harm reduction benefits to the whole population, including adolescents Recognise nicotine use in the counterfactual Undertake coherent market-wide surveillance Monitor all products, including those without PMTA, illicit trade, smoking Detect excessive youth uptake and react Manage emerging unintended consequences