How Evidence Informs the FDA Public Health Standard: Systems Considerations

HOW EVIDENCE INFORMS THE FDA PUBLIC HEALTH STANDARD: SYSTEMS CONSIDERATIONS David B. Abrams, PhDSchroeder 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

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

Public Health StandardComparisons for Protection of Public Health: – Made to never smokers or medicinal NRT usersIn 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: Additional ConsiderationsFramed in terms of risks, benefits, and likelihoods, notcausation: – 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

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 CONSEQUENCESAdapted from: Senge & Lannon-Kim (1991)

Initiation Cessation Rate Rate

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 + availabilityproduction capacity <xxx>

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

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 associationresponse relationship, biological plausibility, coherence) satisfied Yes CAUSAL INFERENCE

TPSAC recommendations for evidence review and classificationClassification 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

Public health standard“Public health standard” calls for the review of the scientificevidence 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

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

Examples of ConsiderationsI. 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 burdenSystems model needed to assess intended and unintended impactPopulation shifts among users, non users and former users.

Perceived Safety of Eclipse Compared to Regular Cigarettes 14% 24% % reduction in risk57% believe60-100% of 0-20%risk is 20-60%eliminated! 60-90% 29% 100% 33% Shiffman, 2004

Examples of ConsiderationsII. No more harm compared to current smokers > Benefit / Harm toPopulation ?TPSAC concluded that the scientific evidence establishes that the removalof menthol cigarettes from the market would benefit public health inthe 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

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 237,317Levy, Pearson, Villanti, Blackman, Vallone, Niaura, Abrams. Modeling the Future Effects of aMenthol 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 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

Industry counter-marketing to consumers

Research Appropriate to the Question(s)Established science from a variety of disciplines - biology topopulation:• 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

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 29

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How Evidence Informs the FDA Public Health Standard: Systems Considerations

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How Evidence Informs the FDA Public Health Standard: Systems Considerations — Presentation Transcript