Do Electronic Cigarettes Have Any Potential for Smoking Cessation? Professor Chris Bullen MBChB, MPH, PhD SRNT Webinar December 8th 2016

Transcription

1 Do Electronic Cigarettes Have Any Potential for Smoking Cessation? Professor Chris Bullen MBChB, MPH, PhD SRNT Webinar December 8th 2016

2 Disclosure statement Affiliations Fulltime employee of the University of Auckland Disclosure - PI on three trials involving e-cigarettes and Co-I on several others - All trials funded through public good grants - No affiliation with the tobacco industry nor have I received personal benefits from the manufacturers or retailers of e- cigarettes.

3 Outline - My context and frame of reference - What are e-cigarettes? - Evidence on their cessation effectiveness - Evidence on their safety - Population health considerations - Reflections and Conclusions

4 My context and frame of reference - From New Zealand, a small island nation with its own unique tobacco control history and epidemiology - National Smokefree 2025 goal - Persistent inequalities in smoking and health - A medical doctor interested in helping to support individuals to quit smoking and improve their health - A public health physician interested in comprehensive populationlevel tobacco control - A health researcher interested in evidence to inform the prevention and management of smoking and its harms.

5 Differing views on e-cigarettes Disruptive technology that will end smoking Huge gains for public health if all smokers adopt e-cigarette use VERSUS A distraction from the tobacco end game A major threat to tobacco control they will discourage quitting, renormalise smoking, recruit new cigarette smokers and strengthen the arm of Big Tobacco

6 Opportunity or Threat? - an evolving frontier filled with promise and peril for tobacco control practitioners, policy makers and regulators (Abrams, 2014) - Opportunity - possibility of genuine tobacco harm reduction and a breakthrough for smokers and tobacco control - Threat - fewer smokers becoming completely abstinent, new addicts recruited and tobacco industry reinvigorated.

7 What are e-cigarettes? Devices whose function is to vaporise and deliver to the lungs of the user a chemical mixture typically composed of nicotine, propylene glycol and other chemicals. - World Health Organisation

8 Assessing e-cigarettes is not easy - Hundreds of different brands and models of e- cigarettes available: 466 in Jan 2014, 11 new brands/month between Differ in nicotine content - content of fluid in cartridge, or fluid in reservoir unique flavours in Jan 2014; 242 new flavours per month between User experience and use patterns (daily or non-daily) - Research ECs? or most popular? Source: Goniewicz 2012; Goniewicz, Hajek & McRobbie 2014; Zhu et al, 2014; Vansickel 2012

9 Herbert A Gilbert 1963 Hon Lik 2003 Evolution

10 Examples of different electronic cigarettes. Source: Grana et al. Circulation, 2014

11 Rapid uptake by smokers why? To try to quit or reduce smoking Acceptability as a cigarette substitute Ability to handle and inhale Throat kick Visible vapour Flavours Speed and dose of nic. Overcome normative barriers Safer than cigarettes Favourable pricing Novelty Supportive subculture Online support Hobby Regulatory vacuum Sales of ECs (global) 10 billion (estimate d) 1.5 billion 3 billion

12 UK smokers are using e-cigarettes for smoking cessation Aids used in most recent quit attempt Percent of smokers trying to stop N=11976 adults who smoke and tried to stop or who stopped in the past year; method is coded as any (not exclusive) use E-cigs NRT OTC NRT Rx Champix Beh'l supp Source: smokinginengland.info/latest-statistic

13 E-cigarettes reduce urge to smoke Source: Bullen et al, Tob Control 2010

14 Variation in nicotine delivery with models: 1 st gen, new gen Source: Farsalinos et al, Sci. Rep. 2014

15 Nicotine delivery also varies by brand 2.4% 2.4% 18mg Source: Goniewicz, Hajek & McRobbie, 2014

16 Cochrane review

17 Aims of review - Primary objective: To evaluate the efficacy of e-cigarettes for helping people who smoke to achieve long-term abstinence. - Secondary objectives 1) to evaluate the efficacy of e-cigarettes for helping smokers to substantially reduce cigarette use 2) To assess the occurrence of adverse effects.

18 Published RCTs with a primary endpoint of quitting Caponnetto (2013) (PlosOne) Bullen (2013) (Lancet) Population Unmotivated to quit Motivated to quit Inclusion criteria 10cpd for at least 5 years, years 10cpd for last year, 18 years Brand Categoria Elusion Sample size Intervention Intervention period 7.2 mg E-cig mg E-cig 0 mg E-cig No behavioural support 16mg E-cig 21mg NRT patch 0mg E-cig Minimal behavioural support 12 weeks 13 weeks (includes one week pre-quit) Follow-up 12 months 6 months Power 75% 80% Primary outcome Verified continuous abstinence at 6 months Verified continuous abstinence at 6 months

19 Outcome measures Primary outcomes - Cessation at the longest follow-up point (at least 6 months from the start of the intervention), ITT using strictest definition of abstinence, preferring biochemical validation. Secondary outcomes - Reduction in cigarette use at the longest follow-up point (at least 6 months from start of intervention), ITT, confirmed by a reduction in biomarkers of exposure. - Any data on adverse events at one week or longer, serious and non-serious, collected from included studies.

20 ECLAT Trial - strengths and limitations Strengths - Early exploratory trial - Double-blind - 12 months follow up - Pragmatic Limitations - No a priori primary cessation outcome specified - No standard treatment comparator - No behavioral support - but 9 points of contact with researchers over 12 months - Lack of statistical power - Low nicotine content e-liquid - Unreliable product - High loss to follow up - 40%

21 ASCEND Trial - strengths and limitations Strengths Limitations - Largest trial conducted to date with cessation outcome - Pragmatic design - Focus on sustained abstinence - Quit rate similar to that seen in NRT trials with limited behavioural support

22 Cessation - Nicotine e-cigarette vs NRT Study Nicotine EC Nicotine Patch RR (95% CI) Bullen % (21/289) 6% (17/295) 1.26 ( )

23 Cessation Nicotine vs Non-Nicotine e-cigarettes Study Nicotine EC Placebo EC RR (95% CI) Bullen % (21/289) 4% (3/73) 1.77 ( ) Caponnetto % (22/200) 4% (4/100) 2.75 ( ) Total 9% (43/489) 4% (7/173) 2.29 ( ) - No significant statistical heterogeneity - RR 2.29 ( )

24 RCTs: 50% reduction Study Nicotine EC Placebo EC RR (95% CI) Bullen % (165/268) 47% (33/70) 1.31 ( ) Caponnetto % (29/178) 13% (12/96) 1.30 ( ) Total 43% (194/446) 27% (45/166) 1.31 ( ) Study Nicotine EC Nicotine Patch RR (95% CI) Bullen % (165/268) 44% (121/278) 1.41 ( )

25 Conclusions - Nicotine e-cigarettes significantly more effective than placebo e-cigarettes for cessation, and significantly more effective than nicotine patches in helping people achieve 50% or greater reduction in smoking - Limited evidence from one RCT that nicotine containing e-cigarettes give similar quit rates at 6 months as NRT.

26 Caveats - Two RCTs were well conducted and at low risk of bias but quality of the evidence overall categorised as low because of the small number of trials on which it is based - Both used 1 st generation products - Both were underpowered - Both offered a low level of behavioural support

27 Duelling Systematic Reviews The Cochrane review excluded three (Adkison 2013; Popova 2013; Vickerman 2013) of these studies but included Grana 2014 and Choi neither detected a significant difference in smoking cessation between smokers that used or did not use ECs at baseline. WHO review (2014) included pooled data from 5 studies (4 longitudinal and 1 cross-sectional) reporting that EC use was associated with a significantly lower chance of quitting smoking (OR=0.61; 95% CI: ). Rahman et al s (2015) systematic review and meta-analysis included Bullen et al and Caponetto et al as well as Brown et al (2014) (cross-sectional),etter et al (2013) (Cohort), Polosa et al (2013) (cohort) and Siegel et al (2011) (cross sectional) [6 studies, n=7551] concluded ECs were modestly effective for cessation and reduction - 20% of users of nicotine-containing Ecs quit but no comparator with usual treatment.

28 18 real world studies, 2 RCTS - 28% lower odds of quitting in EC users vs non users

29 Real-world effectiveness 5863 adults who had smoked within the previous 12 months and made at least one quit attempt during that period with either an e-cigarette only (n=464), NRT bought OTC only (n=1922) or no aid in their most recent quit attempt (n=3477) 25% 20% 15% 10% 20.0% Self reported abstinence adj OR=1.61 (95% CI: ) 10.1% 15.4% 5% 0% adj OR=1.63 (95% CI: ) E-cigarette OTC NRT No aid Brown et al. Addiction

30 Population level potential? - Good if - All smokers take up vaping - All quit smoking: no dual use - No new recruits to smoking - Bad if: - Long term vaping harms not yet known - Smokers deterred from quitting via dual use - Former smokers resume nicotine use - Renormalise smoking and undermine smoking bans - Gateway to smoking among the young

31 How could e-cigarette s potential be harnessed? - Adding behavioural support to NRT improves efficacy - Most vapers receive limited behavioural support - If we added behavioural support to E-cigarettes would this increase cessation efficacy? - Could potentially help the millions of dual users about 2/3 of all vapers - to increase their motivation to quit smoking altogether. - How best to deliver to them?

32 Health Inequalities - Could e-cigarettes reduce inequalities? - Depends on affordability, acceptability and accessibility to people on lower-incomes and poor health - AOD, mental health, NZ Māori - 15% of NZ population, 50% still smoke - 7 years less life than non-māori; 2 of these years are attributable to tobacco smoking - Could E-cigarettes be helpful? - Smokers in LMICs? - More research needed!

33 Are e-cigarettes safe? - Short-term use safe with few AEs reported in trials - 95% safer than smoking? (PH England, RCP) - Increasing number of studies on toxicology of vapour - but quality varies & media representation often misleading - Health effects of long-term frequent use are unknown - Individual safety and population safety

34 Adverse events in Cochrane review - Neither of the RCTs and none of the cohort studies reported any serious adverse events (AEs) considered plausibly related to EC use - Bullen nicotine EC vs. patch (RR 1.00, 95% CI: ) - Caponnetto 2013a - No difference in freq of AEs at 3 or 12 month follow-up - 5 most frequently reported AEs at baseline: cough (26%), dry mouth (22%), shortness of breath (20%), throat irritation (17%), and headache (17%). - The cohort studies show a similar picture: mouth and throat irritation most frequently reported AEs in EC users, dissipating over time - Longest use: 18 months

35 Smart regulation is needed Need regulations that balance benefits with potential harms at individual and population levels. e.g. Controls on sales and marketing and use in some settings; quality standards for devices and e- liquid. However - Products already available in the marketplace including on-line - Limited information available for consumers - Diverse products and use patterns - Tobacco Industry involvement

36 Advice for clinicians - Urgent need to stop smoking - Guideline-based support comes first - Advise patients that: - fully substituting e-cigarettes for tobacco is preferable to dual use - limited knowledge on harms of long-term use - ideally should wean off nicotine - May be helpful as a rescue product for urges to smoke - My view: Patients unwilling to quit smoking or for whom standard cessation treatments are contraindicated or have been tried and failed should not be stopped from trying e-cigarettes, or continuing to use them if they are helping them cut down or quit

37 Science or ideology? - Interpretation of the evidence and communication with policy makers and the public should not be distorted by a priori judgements (West and Brown, 2014) - Respectful, constructive discussion and debate - Common ground and consensus

38 Tobacco Control Goals clarity needed - Smoking abstinence? - Tobacco abstinence? - Nicotine abstinence? - Reducing smoking prevalence? - Reducing smoking harms? - Maximising individual welfare? - Reducing tobacco-related inequalities? - Improving individual and population health?

39 Summary E-cigarettes are a fast evolving product group with potential as an aid for helping many smokers quit Whether their potential can be fulfilled depends on many factors Individual and population health considerations Common ground needed on goals

40 Professor Christopher Bullen Director, National Institute for Health Innovation (NIHI), School of Population Health, The University of Auckland, Auckland, New Zealand.