how evidence informs the fda public health standard: systems considerations
TRANSCRIPT
HOW EVIDENCE INFORMS THEFDA PUBLIC HEALTH STANDARD:
SYSTEMS CONSIDERATIONS
David B. Abrams, PhDSchroeder Institute for Tobacco Research & Policy Studies
Johns Hopkins Bloomberg School of Public [email protected]
PRESENTED AT: STAKEHOLDER MEETINGCENTER FOR TOBACCO PRODUCTS, FOOD AND DRUG ADMINISTRATION
ROCKVILLE, MDTHURSDAY, JUNE 9, 2011
• 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
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 ?
Public Health Standard
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
Public Health Standard:Additional Considerations
"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)
What is Systems Thinking?
Initiation Rate
CessationRate
SmokersPublic
awareness oftobacco health
risk
Tobacco marketingactivities
People quittingsmoking
-
Smoking as asocial norm
People startingsmoking
Tobaccorevenues
+
+
+
+
+
Researchersawarness of
tobacco healthrisk
Funding fortobacco health
research+
++
-
+
Tobacco productsavailability
+
Tobaccoproductioncapacity
+
+
Trend in tobaccocompany revenues
+
-
-
+
<xxx>
Emerging Evidence of Tobacco Harms…
CurrentSMOKERS
Quitters, Former Smokers
Initiation
Funding for tobacontrol program
Tobacco controlprograms
SmokersPublic
awareness oftobacco health
risk
Pressure on tobaccocompanies to reducemarketing activities
Tobacco marketingactivities
+
+
+
-
People quittingsmoking
-
Smoking as asocial norm
People startingsmoking
Tobaccorevenues
+
+
+
+
+
Health care costs
+
Researchersawarness of
tobacco healthrisk
Funding fortobacco health
research+
+
Govt awarenessof tobaccohealth risk +
+
-
Pro-tobaccocontituencies
Anti-tobaccoconstituencies
++ +
+
Tobacco productsavailability
+
Tobaccoproductioncapacity
+
+
+
++
+
+
Trend in tobaccocompany revenues
+
-
-
+
+
Pro and Anti - tobacco vectors: reciprocally influencing, risks, norms, behaviors
CurrentSMOKER
Former Smokers
Initiation
Initiation Rate
CessationRate
Establishing Causal Inference
Statistical association established
Bias excluded
Confounding excluded or neutralized and association persists
Sir Bradford Hill’s Guidelines:Confirmatory criteria of causality (e.g.,
temporality, strength, consistency, dose response relationship, biological plausibility,
coherence) satisfied
CAUSAL INFERENCE
Yes
Yes
Yes
Yes
Non-causal association
Non-causal association
Non-causal association
Non-causal association(or repeat study in larger
sample)No
No
No
No
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
TPSAC recommendations for evidence review and classification
“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
Public health standard
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What data are needed to inform?
Typical Regulatory Standard:• Animal studies• Human exposure studies.• Randomized Controlled Trials• Case studies, clinical studies• Adverse event reports• Epidemiologic studies• Harms to individuals
compared to: non-users, medicinal nicotine, OR users of (LETHAL) cigarettes
Public Health Standard:• Epidemiologic studies• Economic studies• Psychological studies• Sociological studies• Qualitative research• Consumer behavior studies.• Review of tobacco industry
documents• Systems science
– mathematical modeling– social network science– simulation
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 impactPopulation shifts among users, non users and former users.
Examples of Considerations
Perceived Safety of Eclipse Compared to Regular Cigarettes
% reduction in risk
14%
29%
33%
24%
0-20%20-60%60-90%100%
57% believe60-100% ofrisk is eliminated!
Shiffman, 2004
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
Examples of Considerations
Lives savedTOTAL POPULATION
10% change 323,10720% change 478,15430% change 633,252
AFRICAN AMERICANS ONLY10% change 91,74420% change 164,46530% change 237,317
Estimated number of lives saved after menthol ban, 2010-2050
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
• 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
Industry Counter Actions
Industry counter-marketing to consumers
Initiation Rate
CessationRate
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
Research Appropriate to the Question(s)
• 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
Summary
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END