Jean-François ETTER, PhDAssociate ProfessorFaculty of Medicine University of Geneva, Switzerland

RESPADD Paris, 15 Mai 2014

E-cigarettes: utilisation, législation, recommandations

Conflicts of interests

Tobacco industry: - never received any funding, no COI

Pharmaceutical industry- no funding in past 8 years, no COI

E-cigarette industry- plane ticket + hotel (London + China)

Attributable deaths by risk factor, USA

WHO – 1 billion deaths in 21st century

Cancer mortality, USA, 1930-2000

E-cig + nicotine vaporizers: Potential to obsolete cigarettes

Nicotine + tobacco vaporizers: no combustion of tobacco

Without tobacco:

1. E-cigarettes

2. VOKE (BAT: British American Tobacco): nicotine vaporizer (technology of asthma vaporizers)

3. Nicotine pyruvate (PMI: Philip Morris, Jed Rose)

With tobacco:

1. Heated tobacco products (PMI, BAT): - electric heating- charcoal heating

2. Hot air over leaves (Ploom: Japan Tobacco)

Why now?Battery development

3 types: cigalikes, vaporizers, mods

Cigalikes

Vaporizers

Mods

E-cig global sales, $ million

190 350700

1200240 160

150

100

480770

950

1200

0

500

1000

1500

2000

2500

2010 2011 2012 2013USA China International

(source: Philip Morris)

England Toolkit study:Aids used in most recent quit attempt

13

05

101520253035404550

Perc

ento

f sm

oker

s try

ing

to s

top

E-cigsNRT OTCNRT RxChampixBeh'l supp

N=4,164 adults who smoke and tried to stop or who stopped in the past year

E-cig use in Switzerland, 2013

6,7

28,5

1,1

5,5

0,1 0,40

5

10

15

20

25

30

All Daily smokers

%

Ever use In past 30 days Daily use

Source: Monitorage suisse des addictions (OFSP)

Safety, toxicity of e-cigs

Impurities + toxicants found in e-liquids + vapors:- in concentration much lower than in tobacco smoke- often below the levels known to be toxic- heterogeneity, many manufacturers

Passive exposure to second-hand vapor- only partially documented- unlikely to be harmful, but unpleasant- use etiquette, common sense

Diacetyl as ingredient not contaminant (buttery flavor): popcorn lung disease Nicotine

- not harmful at doses used by vapers or users of nicotine patch, gum PG, VG

- appear to be safe when inhaled- but: effects on users with respiratory diseases ?

Flavors: intended for food, not inhalation Long term effects not known (150 puffs per day over several years)

Adverse effects

No serious adverse event was reported in e-cig clinical studies (after 12 months), in particular no clinically significant effect on cardiovascular or respiratory systems

Most frequent symptoms:- irritation, dryness of mouth, throat

Adverse events were reported to FDA and MHRA (UK)- causality ?

One case of lipoid pneumonia reported in the literature Nicotine poisoning

- press release (Israel): 2y old girl dies after drinking e-liquid bottle- failed suicide attempt, women drinks 1500 mg nicotine in e-liquids,

fully recovers

Smoking status of vapers

Across 8 surveys in representative samples of the general population, the proportion of EC users was 2 to 8 times higher in current smokers than in former smokers

Most users = dual users (e-cig + cig)

Sources:Choi. Am J Public Health. 2013Dockrell Nic Tob Res 2013Douptcheva. J Epidemio Comm H 2013Goniewicz. Pediatrics. 2012King. Nicotine Tob Res. 2013McMillen. J Environ Public H 2012Pearson Am J Public Health 2012Regan Tob Control 2011Sutfin Drug Alc Depend 2013

Experimentation and use by never smokers

From 12 surveys in representative samples of the general population UK, USA, Australia, New Zealand, Canada, Poland, Switzerland, Czech Ever use in never smokers :

- range : 0.1% to 3.8%- median : 0.5%

Use in past 30 days, in never smokers :- range : 0% to 2.2%- median : 0.3%

Sources:Camenga Addict Behav 2013Cho. J Adol Health. 2011Choi. Am J Public Health. 2013Corey MMWR 2013Dockrell Nic Tob Res 2013Douptcheva J Epidemio Comm H 2013Goniewicz. Pediatrics. 2012King. Nicotine Tob Res. 2013McMillen. J Environ Public H 2012Pearson Am J Public Health 2012Regan Tob Control 2011Sutfin Drug Alc Depend 2013

Daily use by never smokers

Sources:Douptcheva. J Epidemiol Comm Health. 2013ASH-UK. 2013

Was assessed in 2 surveys in representative samples of the general population

UK, Switzerland

To date, no daily use in never smokers has been reported

Perceived effects on smoking reduction, cessation

In 8 studies in convenience samples of vapers

42-99% of ex-smokers said e-cigs helped them quit smoking

60-86% of smokers said e-cigs helped them reduce cig./day

Sources:ETTER (2010), BMC Public Health, 10, 231.SIEGEL (2011), American Journal of Preventive Medicine, 40, 472-5.ETTER (2011), Addiction, 106, 2017-28.FOULDS (2011) International Journal of Clinical Practice, 65, 1037-42.GONIEWICZ (2013), Drug and Alcohol Review, 32, 133-140.DAWKINS. (2013) Addiction.KRALIKOVA (2013), Chest.FARSALINOS (2013), International Journal of Environmental Research and Public Health, 10, 2500-14.

Effects on smoking cessation: 2 randomized, controlled trials

Italy, New Zealand Modest quit rates, comparable to nicotine patch Used obsolete models that delivered little nicotine Both studies present methodological limitations (even though one

study was published in The Lancet)

Sources:Bullen The Lancet 2013Caponnetto PLOS One 2013

Addiction

Definition: Compulsive use in spite of adverse consequences for the user’s

health, family and social life

The « adverse consequences » element is lacking for e-cigs

Addictiveness of e-cigs

Surveys of vapers:- Vapers are former and current smoker- 97% to 100% of vapers use nicotine-contining e-cigarettes

Thus, e-cigs are nicotine-delivery devices

Addictiveness depends on the speed of delivery to the blood Nicotine is highly addictive when smoked Some users are addicted to the nicotine gum Nicotine patches are not addictive

Speed of delivery for e-cigs: quicker than for nicotine inhaler, but slower than for cigarettes (Bullen, Farsalinos)

Speed of nicotine delivery to the blood:1st generation e-cig, 2nd generation e-cig, tobacco cigarettesSource: Farsalinos et al Sci Rep. 2014; 4: 4133

Are e-cigarettes addictive ?

This is not yet well documented, but it is possible

Some former smokers who were already addicted to nicotine probably use e-cigarettes compulsively

Surveys suggest that addiction to e-cigarettes is weaker thanaddiction to tobacco (but this need confirmation)

Compulsive use of e-cigarettes can be treated- with nicotine patches, which are not addictive- with varenicline- and counseling by a clinician

Is it a public health problem ?

Adverse consequences of long-term vaping are not yet documented

But long-term vaping is much safer than smoking

E-cigs help people quit smoking and avoid relapse

Compulsive use of e-cigarettes can be treated, probably more easily thanaddiction to tobacco

Comparison with nicotine gums: 1% of smokers who quit smoking with nicotine gums remain addicted to

these gums, but… - this is not a public health problem- nicotine gums are sold without a medical prescription- FDA 2013: long-term use of nicotine products not harmful

Summary of evidence

1. E-cigarettes are used by current and former smokers, as a cheaper and safer alternative to tobacco

2. Regular or daily use in non-smokers has not been documented so far

3. E-cigs most certainly help smokers quit or reduce smoking

4. E-cigs are less addictive and less toxic than cigarettes, long-term effects not known

Sources:1)Cho. J Adol Health. 2011 Choi. Am J Public Health. 2013Corey MMWR 2013 Dockrell Nic Tob Res 2013Douptcheva J Epidemio Comm H 2013 Goniewicz. Pediatrics. 2012King. Nicotine Tob Res. 2013 McMillen. J Environ Public H 2012Pearson Am J Public Health 2012 Regan Tob Control 2011Sutfin Drug Alc Depend 20132) Douptcheva et al. J Epidemiol Comm Health. 2013; Zhu et al. PLOS One. Oct 2013; ASH-UK. 20133) Etter (2010), BMC Public Health, 10, 231. Siegel (2011), American Journal of Preventive Medicine, 40, 472-5.Etter (2011), Addiction, 106, 2017-28. Foulds (2011) International Journal of Clinical Practice, 65, 1037-42.Goniewicz (2013), Drug and Alcohol Review, 32, 133-140. Dawkins. (2013) Addiction.Kralikova (2013), Chest. Farsalinos (2013), Int J Environ Res and Public Health, 10, 2500-14.4) On addictiveness of e-cigs: Foulds Int J Clin Pract 2011, Goniewicz Drug Alc Rev 2013, Dawkins Addiction 2013, Farsalinos IJERPH 2013

Should clinicians recommend e-cigarettes for smoking cessation?

Not regulated as a medication, no therapeutic intention

For all smokers : - Say that combustion is the most toxic method of inhaling nicotine, all other methods are safer- Inform about e-cig safety, efficacy- Inform about the nature of nicotine

For non-users of e-cigs :- Recommend approved medications / methods first

For current e-cig users :- Focus on smoking cessation, not e-cig cessation. Help them if they say e-cig helps them, don’t be a barrier on their road to quitting- Recommend to test several products, flavors, nicotine strengths before they find the one that most suits them.- Cigalikes are not very effective, prefer tank systems

In many countries: nicotine allowed only in smoked tobacco or in medications

Currently in many countries, nicotine is available either in :- smoked tobacco (smokeless banned in many countries)- medications (patch, gum, etc.)

For public health, this approach is largely a failure

The most deadly product is cheap + available everywhere

Nicotine replacement therapy- not very appealing- not very effective in the long term (increases smoking cessation

rates by a few percentage points only)

The success of e-cigs challenges this approach

The regulation of nicotine needs to be rethinked, but how ?

Regulation: European Union (EU)

Tobacco Products Directive: article 20 EU Parliament voted February 26, 2014: Opacity, no consultation, many pages of text, behind closed doors. Applies to “cross-border distance sales of e-cigarettes” Disclose list of ingredients + emissions Products should be notified:

- Toxicological data, document effects on health, addictiveness Restrictions on advertising and sponsorship Rejects proposal to regulate e-cigs as medicines Nicotine liquids: containers maxi 10 ml, tanks maxi 2 ml Maxi 20 mg/ml nicotine Only ingredients that do not pose any risks to health E-cigs must deliver nicotine at consistent level Surveillance system for adverse effects

EU Directive

Leaflet: warnings, addictiveness, toxicity'This product contains nicotine which is a highly addictive substance.'

Advertisement is prohibited “any form of public or private contribution to radio programmes with

the aim or direct or indirect effect of promoting electronic cigarettes and refill containers is prohibited”

Where, …, the placing on the market of specific electronic cigarettes or refill containers, …has been prohibited on duly justified grounds in at least three Member States, the Commission shall be empowered… to extend such a prohibition to all Member States

USA « deeming regulation »

Currently : - FDA cannot regulate e-cigs as drugs : court decision Sottera 2010- FDA regulates all non-medicinal nicotine as tobacco : FSPTCA 2009 - E-cigs are currently largely unregulated at federal level- State and local regulations (bans in public places, sales to <18 yr)

FDA (M. Zeller): regulation of nicotine products should be based on a continuum of risk

FDA «deeming regulation» (i.e. for products deemed tobacco) : - consultation procedure began in April, outcome unknown:- register products with FDA, marketed only after FDA review- no claims of reduced risk (unless FDA confirms that scientific

evidence supports that claim)- no sales to youth- health warnings

Harm reduction equation

Harm reduction = Reduced risk x Number who switch

Product toxicity & other risks

Product attractiveness

Consumer preference

0

More regulationLower risk

regulated e-cig “unregulated” e-cig

10 100

cigarettee-cigarettes

0 100

Focus on the right relative risk (Clive Bates)

Perspectives

One of the most important public health debates in recent decades:

To redefine the place of nicotine in society and in the law, and make room for new nicotine products

50 by 25 Decrease the tobacco cigarette market by 50% in 2025

(Clive Bates)

Conclusions

A major innovation that has the potential to save many lives

Safety ?

Efficacy ?

Effective addictive

How to regulate nicotine vaporizers?

Window of opportunity: 2014 (EU Directive, FDA, CH)

Balance public health impact vs risks

Research is urgent: supported by whom?

Training (gap between opinions of vapers vs. NHS staff)

Education of the public, clinicians, journalists, policy makers, legislators

Precautionary principle

The European Commission published useful guidance on the precautionary principle in 2000. It sets out six guidelines. Where action is deemed necessary, measures based on the precautionary principle should be, inter alia:

1) proportional to the chosen level of protection,

2) non-discriminatory in their application

3) consistent with similar measures already taken,

4) based on an examination of the potential benefits and costs of action or lack of action (including, where appropriate and feasible, an economic cost/benefit analysis),

5) subject to review, in the light of new scientific data, and

6) capable of assigning responsibility for producing the scientific evidence necessary for a more comprehensive risk assessment.