E-cigarettes and tobacco-related harm: Evidence and its regulatory implications

1. E-cigarettes and tobacco-related harm: Evidence and its regulatory implications Professor Peter Hajek Wolfson Institute of Preventive Medicine

2. Declaration of interest • I have no links with any e-cigarette manufacturers

3. Contents • Current controversy • Review of evidence • Potential harms and benefits

4. Story so far • E-cigarettes (EC) were invented by Lik Hon in HK in 2003 • Their growing ‘grass root’ popularity is unprecedented • Tobacco industry joined only in 2012 • EC continue to evolve, if they get to match cigarettes in delivering what smokers want, they are likely to replace cigarettes on population scale

5. E-cigarette 5

6. E-cigarettes - second generation 6

7. Current controversy • Over 200 opinion pieces have been published on e-cigarettes so far • Early commentators mostly wanted EC banned or regulated much more severely than cigs, e.g. as medicines • EC compared to NRT, not to cigarettes (impact of pharma industry) • BMA remains anti-EC • More recent comments increasingly warn against favouring cigarettes

8. Strongly negative and positive commentaries

9. EU decision • European Parliament voted on regulating EC as medicines on 8th October 2013 • It turned the proposal down • Such regulation would stop further EC development and spread

10. EU Commission still pushed ahead with anti-EC agenda • EU Commission announced rules much stricter than for cigarettes (from 2016): • Nicotine concentration limited to 1/3 of that provided by average cigarette (20mg/ml) • ‘Consistent delivery’ required • Each product and modification to apply for approval • Small containers only • Countries can ban flavourings

11. How to make a rational decision? • Commentators mostly agree that evidence is needed to consider potential harms and benefits • We have recently reviewed available data* *Hajek, Etter, Benowitz, Eisenberg, McRobbie, Addiction, in press

12. Evidence so far • Survey data • EC content and safety • Effects on smokers

13. Surveys of EC users • EC use was marginal up to 2008-2009, increasing every year since then • So far, only 12%-14% of smokers who try EC become daily users • EC users tend to be younger and better educated, no link to gender

14. EC use in England (Smoking Toolkit data) N=11,666 adults who smoke or who stopped in the past year; increase p<0.001

15. Use by non-smokers • Recent US report: In 2012, among never smokers, Middle School (11-14): 0.5% tried EC; High School (14-18): 0.7% did • In 2011, 40% of US children tried cigarettes by the age of 18; about half will become daily smokers • UK surveys (ASH) – little evidence of use by never smokers or children • Daily use in never smokers: Two surveys looked and found none

17. Interpretation of evidence • Harm: The negligible experimentation was interpreted as highly alarming and even as showing that EC lures kids to smoking • Benefit: People try cigs. If they try EC instead, given no recorded progression, this may reduce smoking uptake. • An empirical question • Evidence: There was a significant decline in youth smoking, no sign of increase

18. Surveys of users • Caution: Responders are enthusiasts • EC consistently helped to quit or reduce smoking, perceived as less addictive • Most popular flavours tobacco, mint and fruit • Most popular strength 18 mg/ml – but 20-30% EC users use >20mg/ml

19. EC content • E-liquids and vapours can contain some impurities and toxicants • Concentrations are much lower than in smoke, and unlikely to affect health • Passive exposure is unlikely to be harmful • Nicotine in vapour and in users linked poorly to nicotine in e-liquid

20. Tobacco Specific Nitrosamine Levels Cahn & Siegel et al Journal of Public Health Policy 2010

21. Interpretation of evidence • Some studies report presence of nitrosamines, metals etc. without commenting on clinical significance; negative comments then present this as evidence of risk • Levels of toxicants detected so far are well within levels considered safe in environment and in inhalation medicines

22. EC safety • No SAEs in any study so far • AEs mostly irritation and cough, same in control conditions and in online forums on adverse effects • FDA monitoring: 47 reports, 8 serious, 2 linked to EC (infant choking on EC cartridge and burns from exploding EC) • Case study of lipoid pneumonia

23. Toxicity of nicotine • Common claim: 30-60mg lethal if ingested • Traced to 19th century made-up figure • Suicide attempts by up to 1,500mg in e-liquid: ‘Voluminous vomiting’ and full recovery in a few hours • Nicotine sulphate in weed killers can kill • Nicotine from tobacco and NRT: Millions exposed, fatal poisonings extremely rare

24. Conclusions on EC safety • Effects on users with asthma and other respiratory diseases and general effects of long-term EC use are not known • Risks, if any, are likely to be a small fraction of the risks of smoking • E-liquid should be in child-proof containers • There is little risk of nicotine poisoning for users

25. Effects on users • EC reduces urges to smoke • EC use leads to reduced smoking and to smoking cessation in healthy smokers, even those not intending to quit; and in smokers with schizophrenia • EC with low nicotine vs patches, no support: Similar small effect on cessation, but EC better on smoking reduction and user approval

26. EC nicotine delivery • Variable, but improving

27. Vansickel et al Addiction 2012 • 20 smokers • 6 x 10-puff bouts on nicotine containing e-cigarette

28. Vinsickel & EissenbergNicotine & Tobacco Research 2012 • 8 experienced e-cig users abstained overnight • Used their own e=cigs • 6 used 18 mg/ml • 2 used 24 mg/ml • Smoked 10 puffs and then had an hour of ad-lib e-cig use • Significant decrease in withdrawal symptoms

29. Nicotine absorption from first and new-generation electronic cigarettes Farsalinos et al, Sci. Rep. 2014 http://dx.doi.org/10.1038/srep04133

30. EC regulation • EC are subject to standard regulation for safety, content, consumer protection etc. • They need to comply with • EU Directive 2001/95/EC(6) on general product safety • EU Restriction of Hazardous Substances Directive (ROHS) • In UK: Chemicals Regulation, in EU, European Regulation on Classification, Labelling and Packaging of Substances and Mixtures • Weights and Measures Regulation; CE (Conformité Européenne); Importing Goods Regulation; etc. • EC are evolving (nicotine delivery, taste, ease of use, etc.) and this allows innovation

31. Proposed EU and US regulation • Administrative and financial burden: Big tobacco can, small manufacturers cannot • Likely impact: • Monopoly of tobacco industry • Stopping e-cig development – changing the licensed products would be too costly and tobacco industry does not want to lose cigs • Keeping EC inefficient and increasing cost • Protecting cigarettes

32. Key outcomes if EC remain a consumer product • Negative: Increased smoking (and smoking related morbidity and mortality) • Positive: Decreased smoking (and smoking related morbidity and mortality)

33. Three routes to the negative outcome: Hypothesis 1 • Chemicals in EC cause morbidity and mortality close to smoking • Evidence so far: Some risk may yet emerge, but without combustion toxicants linked to cancer and CVD, harm, if any, will be a small fraction of the harm from smoking

34. Three routes to the negative outcome: Hypothesis 2 • Smokers who would otherwise quit remain smoking and smoke at the same rate • Evidence: EC use is associated with smoking reduction and cessation. No evidence that it deters from quitting

35. Three routes to the negative outcome: Hypothesis 3 • Gateway for young people who would not try cigarettes, generating entry to smoking higher than EC-generated exit • Evidence: No regular use by never smokers has been recorded so far

36. One route to positive outcomes • EC reduce cigarette use on population level • Evidence: EC reduces cigarette use and facilitates cessation on individual level, positive effects on population level are now appearing as well

37. Population effects in England • Smoking Toolkit Study by Robert West at UCL

38. Aids used in most recent quit attempt (smokinginengland.info/latest-statistic) N=4,935 adults who smoke and tried to stop or who stopped in the past year

40. Prevalence of nicotine/cigarette use Cigarette consumption has decreased as has overall nicotine use N=64,222 adults, decrease p<0.001 for both lines

41. Success rate for stopping in those who tried The success rate in those who have tried to stop smoking is the highest for at least 7 years Base: Smokers who tried to stop n the past year Graph shows prevalence estimate and upper and lower 95% confidence intervals

42. Nicotine use by never smokers and long-term ex-smokers E-cigarette use by never smokers is negligible N=8,380 from Nov 2013

43. The nicotine/cigarette market The cigarette and nicotine market are both declining Nicotine data only from last year smokers nondaily nicotine: <1 pw=0.1, 1+ pw=0.5 N=42,347 adults

44. Cigarette smoking prevalence Cigarette smoking prevalence continues to decline www.smokinginengland.info Base: All adults Graph shows prevalence estimate and upper and lower 95% confidence intervals

45. What does the available evidence suggest? • The positive outcome is much more likely – unless regulators prevent it

46. Additional evidence:Swedish snus

47. Proof of concept • Swedish Snus was banned in Europe on the same pre-cautionary principle invoked for EC regulation (risk to children, ‘gateway to smoking’) • Allowed in Sweden and Norway, enabling a natural experiment • Led to a significant decrease in smoking related morbidity and mortality

48. Daily smoking and snus use in men aged 35-44, Sweden Statistics Sweden/SCENIHR 2008

49. Current smokers, European Union, 2012Eurobarometer 385, 2012

50. Snus use and cancer riskLuo et al, Lancet 2007;329:2015