2015 - David B. Abrams, Ph.D. Truth Initiative Presentation

What science says: operationalizing methods to estimate net public health impact. Data trumps dogma David B. Abrams, Ph.D. [email protected] Professor of Health Behavior and Society, Johns Hopkins Bloomberg School of Public Health. Professor of Oncology Adjunct. Georgetown University Medical Center Lombardi Comprehensive Cancer Center 1

Disclosures Extramural Funding from: NIH / FDA / Westat- subcontracts: –PATH (HHSN 27120110027C) –CECTR (U54 CA189222) –NIDA : R21 DA 036472; K01 DA 027903: –NCI: R01 CA 155369; R01 CA 155489 –Schroeder Institute for Tobacco Research and Policy Studies at Truth Initiative –No support from any industry sources –No other financial relationships to disclose 2

Operationalize the Public Health Standard Calls for the review of the scientific evidence regarding: 1. Risks and benefits 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 4. Individual safety and efficacy and public health IMPACT 3

Eye on the Prize(s): End Game ? • All nicotine and tobacco use in ANY form is evil – Must be stamped out, along with The Industry –No distinction among levels of harm –But 1 billion consumers will die if nothing more is done OR • Eliminate ASAP the real killer: antiquated behavior of Burning Tobacco Leaves – Allow for safer nicotine use to transition from combusted – Keep all nicotine and tobacco away from our kids “If not us, who? if not now, when? ― Hillel the Elder 4

Big Picture Outcome - Reduce Death and Disease Burden in the Population: Harm Minimization “Death is overwhelmingly caused by cigarettes and other combustibles... Promotion of e-cigarettes and other innovative products is... likely to be beneficial where the appeal, accessibility and use of cigarettes are rapidly reduced.” Surgeon General’s Report, 2014, Executive Summary, Pages 14-17 • Maximize benefits: adult smokers switching from deadly combusted cigarettes to safer nicotine or no nicotine – Withholding or fearmongering a substantially less harmful product is a violation of the precautionary principle as combustibles are deadly and defective • Minimize harm: minimize use of nicotine by youth and non-smokers • Allow for transitions from more harmful to less harmful products 5

State Of The Science (Ideology Free Zone): Neutral Framing To Inform Public Health Impact HOW TO OPERATIONALIZE POPULATION IMPACT: BENEFITS AND HARMS – prototype Markov model to frame public health policy – what trajectories are critical tipping points? – patterns of use complex: relative and absolute exposure not obvious – benefits vs. harms, compared to nothing and relative harm – state of the science: uptake of e-cigarette use by non-users – state of the science: impacts on current users. – longitudinal trajectories needed for all the key transitions and states Frameworks and framing the issues – in an open- minded and ideologically free zone - really matters

Formal Markov model: an ideologically free Non- zone. Let data not current Non- current use use dogma speak A compass Roadmap E- Cigarette Dual cigarette use Cobb C. et al. Markov use use Modeling to Estimate the Population Impact of Emerging Tobacco Products: A Proof-of-Concept Study. Former Tobacco Regulatory Science. use 2015;1(2):129-141 7

Non- current use (cig or e-cig) E-cigarette Cigarette Use Use (Experimental (Experimental to regular use Dual use to regular ) use) Former Use (Cig or e- Cobb C. et al. Markov Modeling to Estimate the cig) Population Impact: A Proof-of-Concept Study. Tobacco Regulatory Science. 2015;1(2):129-141 8

Perfect Storm: Combustibles Maximum on All 3 Dimensions Addiction Liability - Nicotine + other additives Combustibles Cigarette, Cigar Pipe, Hookah.. 9 Toxicity - harmfulness

Appeal/Reach, Addiction, Harm: The Triple Framework Flavored Combustible Tobacco; Menthol, little cigars……. Unflavored Combustible Tobacco ….> Addiction Liability - Nicotine + ? Unflavored, less addictive combustible Tobacco ….> Toxicity - harmfulness Developed by DBA and others. 10 Please do not use/cite without permission.

ENDS Challenge: Balancing Nicotine Delivery, Product Appeal and Abuse Potential - Jack Henningfield Absorbable Nicotine (mg/puff) 0.2 0.18 0.16 0.14 0.12 0.1 ? Abuse Potential 0.08 0.06 0.04 0.02 0 1 2 3 4 5 6 7 8 9 10 Generally Appealing to Appealing to Unappealing Smokers Youth Breadth of Appeal

Harm Continuum: Theory to Practice No Harm ( 3 group solution: red, yellow, green. Traffic light labeling system) Toxic REGULATED: DO NOT REGULATED: REGULATED: RGULATED START. STOP CDER CTP MRTP MRTP (Lower MRTP (Higher REGULATED REGULATED toxicant ALL USE IF Pharmacologic nicotine smokeless toxicant Heat-not-burn Combustible POSSIBLE al NRT, delivery smokeless products tobacco (Nothing at all) Zonnic…. systems (e.g., Swedish tobacco’s snus) Cleaner Nicotine ALL NRT, Potentially Reduced COMBUSTIBL ES- ZERO HARM: Alternative Harm DEFECTIVE Use nothing Nicotine AND at all / Delivery Most Harmful Quit all use Systems (ANDS) (BY ORDERS Swedish OF Snus? MAGNITUDE) HARM MINIMIZATION (IDEALLY TO ZERO) 12

Implications and challenges The swirl of data on trial e-cigarette uptake, dual use and use for cessation does not change many policy recommendations ? – • Prudent Product standards to ensure safety and quality BUT without over burdening (Goldilocks)? • Integrated Fast Track nicotine regulation: maximize benefits for cigarette cessation (CDER) and harm minimization (CTP) • Accurate Education on harms and benefits of product classes • Minimize sales, marketing or targeting to appeal to youth of any and all tobacco and nicotine products • Ideology Bias = Blind Men and Elephants, horses and wolves

The good news… smoking is outcome 14.0% Prevalence of Past 30-Day Cigarette Use among 8, 10, & 13.0% 13.2% 12 Graders, MTF -1.3 12.0% 11.9% -1.2 Prevalence 11.0% 10.7% -1.0 10.0% 9.7% 9.0% -1.7 8.0% 8.0% 7.0% 2010 2011 2012 2013 2014 Source: Monitoring the Future, 2014 - Table 1.

Initiation is a Process: harm is trajectory to regular (lifetime) use of deadly combustibles PROGRESSION Exposure Experimentation Regular use least harmful to most harmful Curiosity, Trial use: classes of behavior…… Daily (Ever use, What is net population harm over past 30 day use) of cleaner nicotine..alcohol Lifetime marijuana..traffic accidents.. Common liability suicide,…… combustibles Population Harm: If only if - as a direct causal result of ANDS above the counterfactual - progression leads to combustibles & exceeds all benefits (whole Markovian elephant). vs. other harms

Trajectories Among Non-Users and IMPACT on Population? • Existing data uninformative or lacking to determine: o Causal paths – Longitudinal Trajectories o Conversion rates into/out: trial to regular to combustible – above the counterfactual o Common Vulnerability: travel with other risk behaviors o Context of combustibles: Menthol, flavored cigars, hookah – TOTAL combustibles - appeal, toxicity, addiction o Prevention - Minimize sales/marketing of any tobacco or nicotine delivery product that appeal to non users, especially

For Users of Deadly Combustibles: Outcome is still less population smoking prevalence E-cigarette use FOR Smoking ? CESSATION cessation • For current smokers, will e-cigarettes use impede, improve, or have no effect on cessation (flows over time)? • Typically, RCTs are used to establish efficacy • Bullen et al (2013) – treatment seeking smokers • Caponnetto et al (2013) – non-treatment seeking smokers

C o n tr a d ic to r y Me ta - a n a lys e s :Gla n tz(n e ga tive ) & Mc R o b b ie ( po s itive) : Many ob s er vational s tudies . W ha t t he s c ie nc e re a lly s a ys – rig or or ide ology bia s ? Approach is Blind: meta-analysis vulnerable to • heterogeneous studies that lack sufficient methods rigor Poor Exposure Measures: reason for use, duration, product • used, other quit aids, temporality of use Selection, indication bias: cannot rule out confounders (see • Shiffman et al: Am J Prev. Med 2008;34(2):102–111). Similar concerns in some observational analyses of NRT’s - 80+ RCT’s Replication myth: Multiple uninformative studies create a • FALSE impression of replication (of error). Misleading Flawed studies should NOT be combined: • Uninformative, misleading to use them

Better Measurement of Exposure Cigarette Follow- smoking up abstinence Study period (%) Other outcomes Biener (2014) 2 years Intensive e-cigarette users at baseline 20.4 Intermittent e-cigarette users at baseline 8.5 E-cigarette non-users/triers at baseline 12.4 >50% Quit reduction in attempts Brose (2015) 1 year CPD from baseline to follow-up Daily e-cigarette use at baseline 8.1 13.9 64.9% Non-daily e-cigarette use at baseline 9.5 5.5 52.5% Non-use of e-cigarettes at baseline 12.9 5.7 43.7% Cross- Brown (2014) sectional E-cigarettes used in last serious quit attempt 20.0 NRT used in last serious quit attempt 10.1 No aid in last serious quit attempt 15.4

2014 USA National Health Interview Survey • Current e-cigarette use is extremely low among never smokers (0.4%) and former smokers who quit cigarettes 4 or more years ago (0.8%). • e-cigarette experimentation is most common among current cigarette smokers and young adults, BUT…daily use is highest among former smokers who quit in the past year (13.0%) and older adults. • Compared to daily cigarette smokers, recently quit smokers were more than four times as likely to be daily users of e- cigarettes (AOR: 4.33 [95% CI: 3.08–6.09]). • Suggests daily use of e-cigarettes is associated with cessation of smoking Schoenborn Gindi 2015 . CDC NHIS Nic &Tobac Res. Oct 2015. 1-4: online ahead of print.

Formal Markov model: an ideologically free Non- zone. Let data not current Non- current use use dogma speak A compass- roadmap-frame E- Cigarette Dual cigarette use use use Latest USA NHIS: 1st quarter: Rate of smoking prevalence reduction seems more rapidly down FLOWS OVER TIME Former use ANDS use and dual use is not slowing smoking reduction, may be helping and reducing harms 21

Scaremongering about e-cigarettes is not in the best interest of smokers -- or anyone L o u i s e R o s s P h a r m a c e u t i c a l J o u r n a l O c t 2 9 • There are a number of victims in this war of words: – smokers, who could by now have been encouraged to switch to a safer product to get their nicotine; – their families, including their children, who could have benefited from having a smoke-free environment and more money in the household budget; – and frontline healthcare professionals who want to know what to say about this rapidly evolving technology when their patients ask them. Framing and telling the truth as best we can 22

Scaremongering about e-cigarettes is not in the best interest of smokers L o u i s e R o s s P h a r m a c e u t i c a l J o u r n a l O c t 2 9 • For almost two years now, I have both watched and participated in this battle between public health heavyweights, researchers, commentators, media pundits, health professionals, vaping advocates and the general public. Every time there is a ray of hope that evidence and common sense will triumph over prejudice, risk aversion and ideology, another faction will emerge to try to crush it with doubt and suspicion. Framing and telling the truth as best we can 23

Four centuries ago Sir Francis Bacon: “human understanding is no dry light but receives infusions from the will and affections.” • Lives of smokers and future smokers are at stake in the shifting tobacco control landscape. • Fears of unknown consequences fuel strong emotion, cloud a scientific approach to health policy, a rush to over interpret sparse data .. and mislead everyone. REF: Abrams, Niaura. 2015. Importance of science-informed policy: what the data really tell us about e-cigarettes. Israel Journal of Health Policy Research. 4:22 This is about the People, the People, the People (per Dr. M. Glover, NZ). Its not about us or who is remembered 24

Food for future thought: How to proceed? ideology cuts both ways: reinforces in a distancing spiral • Ultimately, shared commitment to public health • What antagonizes and what helps reconcile partners across the globe/pond? Don’t antagonize. Don’t exaggerate your beliefs. (Its the war not the battle) • Use science/data to inform and open hearts and minds • Opportunity is NOW: The world IS changed by ANDS. Will you be left in the dustbowl of history, be marginalized and ignored, or remembered as one of the Founding Mothers and Fathers? 25

Food for future thought: Truth, reconciliation joining for shared action : 1. Keep doing what we’re doing, but doom a generation of smokers to preventable suffering and misery OR 2. Change the market: First use noncombustible nicotine products to obsolete combustibles while minimizing attraction to youth and non users. • Beware of Ideology and fear – open hearts to what the science really says • Nicotine is here to stay. Must be managed as a consumer product. • Care about consumers: accountability / responsibly by the industries, marketers, policymakers, advocates. • Clearly inform the public with dramatic, life-saving impact. Harm minimization (vs. continued insistence on total abstinence). • Tell young people the truth. This has (and always will be) the most effective way to prevent young people from becoming the next generation of combustible tobacco users. Don’t use at all - but if you do, reduce harm • Go long: Obscuring the facts has never been an effective long term strategy. In a world of instant information, misleading only weakens all our credibility. 26

Food for future thought: Truth, reconciliation joining for shared action : Action: Global deliberation: Rethink, reboot, and reframe nicotine in the absence of combustion. Needed, a Comprehensive Framework. • What questions need to be raised and answered? • How can framework align and guide core values - industries, policy and practice • Within a public health standard that embraces the whole population – relative harms proportional to each product class – complex trajectories/transitions of use behaviors - Flows over time. • Accept we cant stamp out nicotine and it can have benefits… • Given innovation in delivery modes, costs and appeal- displace combustibles Can we end up seeing nicotine not as the main problem anymore, but part of the solution against the burning cigarette? Is nicotine enemy, new friend, frenemy of sorts Do I not destroy my enemy when I make him my friend? Abraham Lincoln 27

Thank You [email protected] 28