1. HOW EVIDENCE INFORMS THE
FDA PUBLIC HEALTH STANDARD:
SYSTEMS CONSIDERATIONS
David B. Abrams, PhD
Schroeder Institute for Tobacco Research & Policy Studies
Johns Hopkins Bloomberg School of Public Health
dabrams@legacyforhealth.org
PRESENTED AT: STAKEHOLDER MEETING
CENTER FOR TOBACCO PRODUCTS, FOOD AND DRUG ADMINISTRATION
ROCKVILLE, MD
THURSDAY, JUNE 9, 2011

2. Public Health Standard
• FDA may issue tobacco product standards
appropriate for the protection of the public health
• The public health standard is new
• Differs from the traditional “safe and effective”
standard for drugs and medical devices,
Because…
• Smoking is neither safe nor effective – it is lethal
when used as intended
• Focused broadly on population not on individual

3. Public Health Standard
Comparisons for Protection of Public Health:
– Made to never smokers or medicinal NRT
users
In Contrast to:
– Demonstrating no more risk than that of
current smokers (no worse impact than the
most lethal product available)
– High bar … low bar ?

4. Public Health Standard:
Additional Considerations
Framed in terms of risks, benefits, and likelihoods, not
causation:
– Multiple pathways - from biological to neuroscience to
behavior to population impact
– Calls for systems integration of evidence in decision
making - knowledge synthesis
– Use various research designs, measures, time frames,
methods, appropriate to the determination at hand.
– There is no “one way”, no narrow, gold standard criterion
Hence the need for an Equipoise Standard

5. What is Systems Thinking?
"Systems thinking is a discipline for seeing wholes,
recognizing patterns and interrelationships, with
non-linear dynamic interactions, social network
effects (new norms / fads), short and delayed
feedback loops...”
Intended and Unintended CONSEQUENCES
Adapted from: Senge & Lannon-Kim (1991)

6. Initiation Cessation
Rate Rate

8. Emerging Evidence of Tobacco Harms…
Funding for
tobacco health
Researchers + research
awarness of
tobacco health
risk
Current +
+
SMOKERS Public
Smokers awareness of
- tobacco health
Tobacco + risk
+
revenues +
+ People starting
+ Initiation
+ smoking
People quitting
Smoking as a Quitters,
Trend in tobacco + - smoking
social norm
company revenues - Former
+
Smokers
+ -
+ Tobacco marketing
Tobacco products
activities
Tobacco + availability
production
capacity
<xxx>

9. Pro and Anti - tobacco vectors:
reciprocally influencing, risks, norms, behaviors
Pro-tobacco Govt awareness Anti-tobacco
contituencies of tobacco
constituencies
health risk + +
+ + + +
++ + Funding for
tobacco health
+
Researchers + research Funding for toba
Health care costs awarness of control program
tobacco health
risk
+
+ +
+
Current Public
Smokers awareness of Tobacco control
SMOKER - tobacco health+ programs
risk
Tobacco +
+
revenues Initiation +
+ People starting
+ + smoking People quitting
Smoking as a Former
Trend in tobacco social norm + - smoking
company revenues
Smokers
-
+
+ +
-
+ Tobacco marketing Pressure on tobacco
Tobacco products companies to reduce
activities-
Tobacco + availability marketing activities
production
capacity

10. Initiation Cessation
Rate Rate

13. Establishing Causal Inference
Non-causal association
Statistical association established No (or repeat study in larger
sample)
Yes
Non-causal
Bias excluded No
association
Yes
Confounding excluded or neutralized and Non-causal
No
association persists association
Yes
Sir Bradford Hill’s Guidelines:
Confirmatory criteria of causality (e.g.,
Non-causal
temporality, strength, consistency, dose No
association
response relationship, biological plausibility,
coherence) satisfied
Yes
CAUSAL INFERENCE

16. TPSAC recommendations for
evidence review and classification
Classification scheme: Based around concept of equipoise
1. The evidence is sufficient to conclude that a
relationship is more likely than not
2. The evidence is sufficient to conclude that a
relationship is at least as likely as not
3. The evidence is insufficient to conclude that a
relationship is more likely than not
4. There is insufficient evidence to make a
determination of strength of evidence

17. Public health standard
“Public health standard” calls for the review of the scientific
evidence regarding:
1. Risks and benefits of the tobacco product standard to the
population as a whole, including both users and non-
users of tobacco products;
2. Whether there is an increased or decreased likelihood
that existing users of tobacco products will stop using
such products; and
3. Whether there is an increased or decreased likelihood
that those who do not currently use tobacco products,
most notably youth, will start to use tobacco products
17

18. What data are needed to inform?
Typical Regulatory Standard: Public Health Standard:
• Animal studies • Epidemiologic studies
• Human exposure studies. • Economic studies
• Randomized Controlled Trials • Psychological studies
• Case studies, clinical studies • Sociological studies
• Adverse event reports • Qualitative research
• Epidemiologic studies • Consumer behavior studies.
• Harms to individuals • Review of tobacco industry
compared to: non-users, documents
medicinal nicotine, OR • Systems science
users of (LETHAL) – mathematical modeling
cigarettes
– social network science
– simulation

19. Examples of Considerations
I. Reduced Individual Harm > Benefit/Harm to Population?
• Light/low tar product claims, labels – lessons learned
• continuum of harm reduction from medicinal to combustible
• Snus, e-cigarettes, and future recreational nicotine delivery?
• Measures of exposure: intermediate biomarkers.
• Measures of harm perception at individual level (not necessarily of
exposure) -- perception can change behavior and harm impact
• Measures of population impact on consumer behavior, use,
exposure, disease burden
Systems model needed to assess intended and unintended impact
Population shifts among users, non users and former users.

20. Perceived Safety of Eclipse Compared to
Regular Cigarettes
14%
24% % reduction
in risk
57% believe
60-100% of 0-20%
risk is 20-60%
eliminated! 60-90%
29% 100%
33%
Shiffman, 2004

23. Examples of Considerations
II. No more harm compared to current smokers > Benefit / Harm to
Population ?
TPSAC concluded that the scientific evidence establishes that the removal
of menthol cigarettes from the market would benefit public health in
the United States.
– Menthol is linked to smoking initiation, particularly among youth and
African Americans (above equipoise)
– Menthol is also linked to lower rates of successful smoking cessation
particularly among African-Americans (above equipoise)
– Insufficient evidence that Menthol adds harm to the individual
smoker, compared to non-menthol smokers

24. Estimated number of lives saved
after menthol ban, 2010-2050
Lives saved
TOTAL POPULATION
10% change 323,107
20% change 478,154
30% change 633,252
AFRICAN AMERICANS ONLY
10% change 91,744
20% change 164,465
30% change 237,317
Levy, Pearson, Villanti, Blackman, Vallone, Niaura, Abrams. Modeling the Future Effects of a
Menthol Ban on Smoking Prevalence. Am J Public Health. Published online ahead of print May 12,
2011: e1-e4. doi:10.2105/AJPH.2011.300179

25. Industry Counter Actions
• Industry report: “Menthol Cigarettes: No Disproportionate Impact on
Public Health” (3/11)
– Uses SGR individual causality framework to assess evidence: “This
approach contrasts sharply with TPSAC’s adoption of an
unorthodox standard using the amorphous concept of
equipoise, which historically has been used to address issues not
relevant here – such as how to ethically conduct randomized clinical
trials or award veterans’ benefits.”
– Same Playbook: Undermine, discredit, cast doubt on the science.
– Déjà vu all over again: Fisher, R. A. Alleged dangers of cigarette
smoking. Br. Med. J.. 2: 518, 1958. In: Wynder. E. Cancer Epidemiol
Biomarkers Prev. 1998;7:735-748

26. Industry counter-marketing to consumers

27. Initiation Cessation
Rate Rate

28. Research Appropriate to the Question(s)
Established science from a variety of disciplines - biology to
population:
• Broad population level standard, not a narrow individual one
• Equipoise is strong science beyond the traditional Randomized
Trial
• Canary in the coal mine concept: rapid research, real time
assessment technology, surveillance pre- and post-market
• Action must not subvert current efforts to reduce harms at
population level
• When in doubt do no harm.
• Science is never certain; act on what is best at the time

29. Summary
• Public Health Standard: risks, benefits and likelihoods NOT
CAUSATION, and not compared to current smokers only
• Focus on individual and population. Decisions based on knowledge
synthesis
• systems analysis: equipoise, delayed feedback loops (pre and post
surveillance), early warning systems, impact on consumer behavior
• Lack of data is not a reason to lower the standards
• Consider how tobacco use behavior will change – Longitudinal
Surveillance, social networks, mathematical modeling, real-time tracking
• Ultimately it’s about benefit to public health as a whole
• Decision making in appropriate context, based on best available
evidence
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30. END