Do Electronic Cigarettes Have Any Potential for Smoking Cessation?

Professor Chris Bullen MBChB, MPH, PhD

SRNT Webinar December 8th 2016

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.

- 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

Outline

-  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 population-

level tobacco control -  A health researcher interested in evidence to inform the

prevention and management of smoking and its harms.

My context and frame of reference

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”

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.

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

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 2012-14 - Differ in nicotine content - content of fluid in

cartridge, or fluid in reservoir - 7764 unique flavours in Jan 2014; 242 new

flavours per month between 2012-14 - User experience and use patterns (daily or

non-daily) - ‘Research ECs?’ or ‘most popular’?

Source:Goniewicz2012;Goniewicz,Hajek&McRobbie2014;Zhuetal,2014;Vansickel2012

Evolution

HerbertAGilbert1963HonLik2003

Examples of different electronic cigarettes.

Source: Grana et al. Circulation, 2014

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

20 39 82 195 500

1.5billion

3billion

10billion(estimate

d)

0

2000

4000

6000

8000

10000

12000

2008 2009 2010 2011 2012 2013 2014 2017

SalesofECs(global)

UK smokers are using e-cigarettes for smoking cessation

Source: smokinginengland.info/latest-statistic

“Aidsusedinmostrecentquitattempt”

0

5

10

15

20

25

30

35

40

45

50

Percen

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erstrying

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E-cigs

NRTOTC

NRTRx

Champix

Beh'lsupp

N=11976 adults who smoke and tried to stop or who stopped in the past year; method is coded as any (not exclusive) use

Source:Bullenetal,TobControl2010

E-cigarettesreduce urge to smoke

Variation in nicotine delivery with models: 1st gen, ‘new’ gen

Source: Farsalinos et al, Sci. Rep. 2014

Nicotine delivery also varies by brand

2.4%

2.4%

18mg

Source:Goniewicz,Hajek&McRobbie,2014

Cochrane review

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.

Published RCTs with a primary endpoint of quitting

Caponnetto(2013)(PlosOne)

Bullen(2013)(Lancet)

Population Unmotivatedtoquit Motivatedtoquit

Inclusioncriteria

≥10cpdforatleast5years,18-70years

≥10cpdforlastyear,≥18years

Brand Categoria Elusion

Samplesize 300 657

Intervention

7.2mgE-cig7.2-5.4mgE-cig

0mgE-cig

Nobehaviouralsupport

16mgE-cig21mgNRTpatch

0mgE-cig

Minimalbehaviouralsupport

Interventionperiod

12weeks 13weeks(includesoneweekpre-quit)

Follow-up 12months 6months

Power 75% 80%

Primaryoutcome

Verifiedcontinuousabstinenceat6months

Verifiedcontinuousabstinenceat6months

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.

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%

Strengths

-  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

Limitations

ASCEND Trial - strengths and limitations

Cessation - Nicotine e-cigarette vs NRT

Study NicotineEC NicotinePatch RR(95%CI)

Bullen2013 7%(21/289) 6%(17/295) 1.26(0.68–2.34)

Cessation – Nicotine vs Non-Nicotine e-cigarettes

- No significant statistical heterogeneity - RR 2.29 (1.05-5.96)

Study NicotineEC PlaceboEC RR(95%CI)

Bullen2013 7%(21/289) 4%(3/73) 1.77(0.54–5.77)

Caponnetto2013 11%(22/200) 4%(4/100) 2.75(0.97–7.76)

Total 9%(43/489) 4%(7/173) 2.29(1.05–4.96)

RCTs: ≥ 50% reduction

Study NicotineEC PlaceboEC RR(95%CI)

Bullen2013 62%(165/268) 47%(33/70) 1.31(1.00–1.70)

Caponnetto2013 16%(29/178) 13%(12/96) 1.30(0.70–2.44)

Total 43%(194/446) 27%(45/166) 1.31(1.02–1.68)

Study NicotineEC NicotinePatch RR(95%CI)

Bullen2013 62%(165/268) 44%(121/278) 1.41(1.20–1.67)

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.

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 1st generation products - Both were underpowered - Both offered a low level of behavioural support

Duelling Systematic Reviews

The Cochrane review excluded three (Adkison 2013; Popova 2013; Vickerman 2013) of these studies but included Grana 2014 and Choi 2014 - 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: 0.50-0.75). 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.

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

‘Real-world’ effectiveness

20.0%

10.1%

15.4%

0%

5%

10%

15%

20%

25%

E-cigarette OTCNRT Noaid

Selfreportedabstinence

adjOR=1.61(95%CI:1.19-2.18)

adjOR=1.63(95%CI:1.17-2.27)

Brownetal.Addiction.2014.

5863adultswhohadsmokedwithintheprevious12monthsandmadeatleastonequitattemptduringthatperiodwitheitherane-cigaretteonly(n=464),NRTboughtOTConly(n=1922)ornoaidintheirmostrecentquitattempt(n=3477)

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

- 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?

How could e-cigarette’s potential be harnessed?

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!

- 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

Are e-cigarettes safe?

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 2013

-  nicotine EC vs. patch (RR 1.00, 95% CI: 0.85-1.18) - 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

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

- 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 contra-indicated 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

Advice for clinicians

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

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

Tobacco Control Goals – clarity needed

• 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

Summary

Professor Christopher Bullen Director, National Institute for Health Innovation (NIHI), School of Population Health, The University of Auckland, Auckland, New Zealand. c.bullen@auckland.ac.nz www.nihi.auckland.ac.nz