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
1. 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
2. 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
3. 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