CWAG Presentation Park City. Utah. 21 st July 2014

2. Regulatory Science to Policy: Update on e-cigarettes.David B. AbramsThe Schroeder Institute For Tobacco Research And Policy Studies at Legacy.The Johns Hopkins Bloomberg School of Public HealthGeorgetown University Medical Center / Lombardi Comprehensive Cancer Center CWAG Presentation Park City. Utah. 21st July 2014

3. disclosures • Funding from NIH – FDA • No other financial relationships to disclose • Legacy Foundation support • No support from any industry sources

4. Update on e-cigarettes • Nicotine and Public Health • Harm Reduction • Will alternative nicotine delivery systems increase or decrease cigarette use ? How can prudent regulation help and not hinder ?

5. Emerging Tobacco & Nicotine Products: DISRUPTIVE: Evolution / Revolution?Ending the cigarette century before 100th SGR

6. 20 million deaths: more than in all the American wars since founding our nation • 5.6 million children alive today • and 480,000 adults each year • from their tobacco use behavior: primarily combustible products – cigarettes, cigars, hookah, pipe, roll your own…Burn it and you get burned will die prematurely U.S. Department of Health and Human Services. The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2014.

7. Major Shift: Harm Reduction ? Despite 50 years progress, reduction in combustible cigarettes has slowed ... As articulated in the 2014 Surgeon General’s 50th anniversary Report. Executive Summary (pages 15-17): “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.” ….and their cost is increased

8. Nicotine and Public Health Are e-cigs essentially unregulated NRT ?

9. Comparison between 1st, new, and conventional cigarette

11. Need overall Nicotine Regulation Policy that bridges CTP and CDER • Center for Tobacco Products • Cigarettes • Roll-your-own tobacco • Smokeless tobacco • Hookah tobacco • Cigars/cigarillos/LCCs • E-cigs for harm reduction • Next Generation Products (Aerosol, Pyruvate, Cleaner Nicotine) • Center for Drug Evaluation & Research • Pharma – NRT, Chantix, Buprorion • Other medications for cessation • RJR Zonnic:Package, Price, Placement • ? E cigs for cessation

12. What we know?: State of the science on e-cigarettes - ENDS • Product features and design • Health and safety • Advertising and Patterns of Use: Youth and Adults • Consumer perceptions: • harm reduction/cessation of combustibles or • Blurring the boundaries between products & poly use • Evolving e-cig industry: Big tobacco vs. independents • Policy considerations: benefits vs. harms

14. Public Health Impact: Zero Tolerance and Harm Reduction Ideology: Data vs Dogma Combusted Tobacco: Cigarettes, Cigars Pipe, Hookah….. Non-Combusted Tobacco and Nicotine Products: ?? Next Generation: Pyruvate Swedish SNUS e-cigs ENDS Abuse Liability “Appeal” American Snus Smokeless Dissolvables Cessation Behav, NRT’s: inhaler patch gum… Toxicity (“Harmfulness”)

15. Cessation and used in quit attempts: growing evidence good as NRT NRT OTC: Nicotine replacement therapy bought over the counter; Med Rx: Prescription medication; NHS: NHS Stop Smoking Service; E-cig: Electronic cigarette

16. YOUTH Patterns of USE. (Experimenting only and over 90% already use conventional cigs). • Adults: Awareness (76%) and use (21%) is growing fast among current smokers and young adults. Perceived as less harmful. • Youth (CDC MMWR 2013) • Use doubledmiddle and high school students 2011–2012, estimated 1.78 million students ever used.

20. Conclusions and Relevance  Use of e-cigarettes was associated with higher odds of ever or current cigarette smoking, higher odds of established smoking, higher odds of planning to quit smoking among current smokers, and, among experimenters, lower odds of abstinence from conventional cigarettes. Use of e-cigarettes does not discourage, and may encourage, conventional cigarette use among US adolescents • Electronic Cigarettes and Conventional Cigarette Use Among US Adolescents: A Cross-sectional Study. Lauren M. Dutra, ScD1; Stanton A. Glantz, PhD1 • JAMA Pediatr. Published online March 06, 2014. doi:10.1001/jamapediatrics.2013.5488

21. Patterns Of Tobacco Use And Dual Use In U.S. Young Adults: The Missing Link Between Youth Prevention And Adult Cessation • 51% had ever smoked cigarettes. First product used: 73% cigarettes, 11% cigars, 5% little cigars/cigarillos/bidis, 4% hookah • 32%of ever users (18-34) reported product initiation after the age of 18 • Of 23% of young adult current users, 30% report dual use. Among dual Users: cigars 23%, little cigars 26%, hookah 17%, dip snuff 12%, chewing tobacco 12%, e-cigs 9%, snus 7%, dissolvables 3% • Dual use - higher in younger adults, males, less than high school education, and those not able to meet their expenses. • Daily cigarette use was similar between dual use and cigarettes only use (no harm reduction due to less cigarettes, rather a harm increase?) Rath J, Villanti A, Abrams D, Vallone D. Patterns of Tobacco Use and Dual Use in U.S. Young Adults: The missing link between youth prevention and adult cessation. Journal of Environmental and Public Health. 2012.

22. Robust ongoing surveillance of NCP advertising is critical to inform the FDA and protect public health. • Both commercial advertising and public health media campaigns must ensure that content is not misleading and educates consumers about harm based on the available science. • The way messages are framed have the potential to decrease tobacco use by promoting rather than undermining cessation of combusted products and/or encouraging exclusive use of less harmful NCPs rather than poly-use of combusted and NCPs.

23. 7. Their ads say, “Switch, Don’t Quit.” Tobacco companies have long tried to discourage smokers from quitting by marketing cigarette changes as reducing health risk. Some e-cigarette ads carry a similar message.

24. SCIENCE Questions: SUMMARY • Less harmful than cigarettes - when good quality can be regulated to be close to Pharama grade NRT. Some ingredients can produce harmful chemicals when heated (coloring / flavors) • How can does e-cigarette use and marketing maximize benfits and reduce harms and affect current smokers? • Delay cessation? Promote cessation? • Reduce cigarette consumption or give the impression of less harm because of imagined reduced cigarette consumption? • Dual use when one can not smoke and alleviate discomfort • Do e-cigarettes encourage former smokers to return to nicotine use and relapse to cigarette smoking? • How do e-cigarettes affect non-smokers ? • Potential uptake among youth and young adults

25. Nicotine and

26. Harm reduced products update: Fiore, Schroeder, Baker. NEJM. Jan 2014; Abrams D JAMA Jan 2014 Communicate intelligently about harm reduction Policy and Practice Proportional to HARM • Focus on eliminating combustible tobacco products - Not all nicotine-containing products are equal… • Even if some who give up combusedswill continue indefinitely using: FDA-approved medicines, e-cigarettes, or smokeless (least harm is Swedish Snus). "New approaches must be adopted if we are to dramatically reduce the harms over the next decade. Goal requires that we recognize the unequal dangers resulting from combustible tobacco use.” CAN E-cigarettes make lethal combustibles obsolete?

27. Conclusions • Stakes are high; lethality of combusted tobacco is worse than we thought • Alternative frameworks of addiction/appeal/harm are available • Taxes and Policies: Proportional to Harm of product class • End game strategies aided by future approaches and devices for nicotine delivery that better substitute for the cigarette pridetn regulation maximize benefits minimize harms • Promotion of e-cigarettes and other innovative products is much more likely to be beneficial in an environment where the appeal, accessibility, promotion, and use of cigarettes are being rapidly reduced

28. Harm Reduction: Policy and Practice Principles • Taxes and Policies: Proportional to Harm of product class • End game strategies aided by future approaches and devices for nicotine delivery that better substitute for the cigarette • Promotion of e-cigarettes and other innovative products is much more likely to be beneficial in an environment where the appeal, accessibility, promotion, and use of cigarettes are being rapidly reduced

29. Thank you

30. Excerpts from: Endingtobacco smoking in Britain; Radicalstrategies for prevention and harm reduction in nicotineaddiction Royal College ofPhysiciansof London, 2008. People smoke because they are addicted to nicotine, but nicotine itself is not especially hazardous; it is the other constituents of tobacco smoke that cause most of the harm. Use of smoke-free nicotine would benefit smokers directly by reducing the personal harm caused by nicotine addiction. “In Sweden, the availability and use by men of an oral tobacco product called snus, one of the less hazardous smokeless tobacco products, is widely recognised to have contributed to the low prevalence of smoking in Swedish men and consequent low rates of lung cancer.”

31. New FDA proposed deeming and future rulemaking • Restrict Sales to over 18 years of age, no free samples. • Warning Label that nicotine can be an addictive substance • Registration, and Product disclosure • Product standards, safe ingredients, child resistant packages • Substantial equivalence or new product application 2yr grace • MRTP applications to claim reduced harm: individual and population standard. Pre-approval and post-market surveillance • Advertising on TV and Targeting youth ? • Flavors attractive to youth (candy) ? • Therapeutic claims for smoking cessation? • Need comprehensive nicotine / tobacco regulatory policy

32. Lessons from the united kingdom • Department of Health committed in its 2011 Tobacco Plan to “develop new approaches to encourage tobacco users who cannot quit to switch to safer sources of nicotine” • In 2013, both the UK Medicines and Healthcare products Regulatory Agency (MHRA) and the National Institute for Clinical and Healthcare Excellence (NICE) issued guidances embracing tobacco harm reduction and a “light-touch” approach to regulating nicotine-containing products as medicines • Wide array of approved uses (e.g., reduce to quit, smoking reduction, temporary abstinence, maintenance) • A handful of applications are apparently pending and the first approval is expected this year • What could FDA glean from this experience?