1 Products for smoking cessation University College London March 2014 Robert West

Declaration of interest I receive research funds and undertake consultancy for companies that develop and manufacture smoking cessation medications (Pfizer and J&J) I am co-director of the UK National Centre for Smoking Cessation and Training I am a trustee of the stop-smoking charity, QUIT My salary is funded by the charity, Cancer Research UK 2

How to stop smoking 3 Get Ready Go Keep going Decide on a ‘quit smoking rule’ Decide on a quit point Lay the ground work Apply the quit smoking rule Do what it takes to stick to the rule

4 Addiction to cigarettes I really want to stop smoking: it’s costing me money and it will probably kill me Just smoke!

5 The battle over time between resolve and urge to smoke Urge to smoke Time When the urge is stronger than resolve and cigarettes are available, a lapse will occur Resolve Strength of urge

6 The role of treatment is to keep these lines as far apart as possible Urge to smoke Time Resolve Strength of urge

Evaluating interventions (APEASE) 1 To identify optimal treatment options to promote smoking cessation taking account of: –Affordability –Practicability –Effectiveness (and cost-effectiveness) –Acceptability –Safety (or side effects) –Equity 7 1 Michie et al (2014) The BCW Guide to Designing Interventions. London: Silverback Publishing

Support for smoking cessation Behavioural support –Advice, discussions, exercises designed to address social and psychological aspects of the problem Pharmacotherapy –Medicines (including nicotine products) designed primarily to reduce craving and withdrawal symptoms 8

The role of behavioural support 1.Reduce motivation to smoke 2.Bolster commitment to abstain 3.Enhance ability to cope with cravings 4.Ensure effective use of pharmacotherapy 9

Internet-based interventions 10 Internet interventions can –provide information and advice –display audio and video –provide an opportunity for interaction –be tailored to users’ needs and preferences –track progress

Text messaging services 11 Text messaging can –provide information and advice –provide motivational messages –provide support at any time

Written materials Books for smoking cessation can –Explain why it is often hard to stop –Motivate and inspire –Advise on best ways of stopping –Advise on how best to use those methods 12

Behavioural support: efficacy 13 Stead et al 2012, Cochrane 1 Pro-active telephone vs reactive: N=24,994 Individual vs brief advice: N=7,855 Group vs self-help: N=4,375 Internet vs nothing: N=2,960 Text messaging versus control messages: N=9,110 Written materials: N=15,117 95% confidence intervals from meta-analyses

Smoking cessation websites 14 Civljak 2010 Cochrane Reviews

Smartphone applications Apps can –Provide the functions of websites at any time –Use a range of mobile sensors –Upload data 15 Percentage95% confidence interval Percentage of users who recorded at least 28 days’ abstinence

Potential reach of websites and apps 16

The role of pharmacotherapy 1.Reduce the strength, duration or frequency of urges to smoke 2.Reduce unpleasant withdrawal symptoms 3.Reduce the pharmacological reward from smoking 17

Licensed medicines NRTtransdermal patch, gum, inhaler, lozenge, nasal spray, mouth spray, and oral film in varying doses and in combinations can be used for smoking reduction use for ≥8 weeks possibly starting before quit date Varenicline partial agonist binding with high affinity to  4  2 nAch receptor increase dose over 7 days then 1mg twice daily for ≥11 weeks or 23 weeks Bupropionunknown mechanism of action use for 8 weeks starting 1 week before quit date Nortriptylineunknown mechanism of action use mg/day for ≥10 weeks starting 1 week before quit date Cytisine 1 partial agonist binding with high affinity to  4  2 nAch receptor use for ≥4 weeks starting 1 week before quit date 18 1 Licensed in some European countries

Affordability Ability within a realistic budget for access to the intervention by all those who could benefit from it Levels: –High: cheaper than smoking –Medium: about the same as smoking –Low: more expensive than smoking 19

Affordability of current medicines InterventionAffordability NRT OTC 1 Moderate NRT for smoking reductionModerate Single form NRT with supportModerate Dual form NRT with supportLow Pre-treated NRT patchLow Varenicline with supportLow Bupropion with supportModerate Nortriptyline with supportModerate Cytisine with supportHigh 20 1 Bought ‘over the counter’ without professional support

Practicability Ability for the intervention to be accessed and used as required To be practicable medicines must: –be easy to use as directed –have adequate health professional support available if needed –have adequate safety monitoring in place –be able to be tailored to suit different smokers Levels: –High: easy to use, support and monitor –Moderate: some problems –Low: serious problems 21

Practicability of current medicines InterventionPracticability NRT OTC 1 Moderate NRT for smoking reductionModerate Single form NRT with supportModerate Dual form NRT with supportModerate Pre-treated NRT patch with supportModerate Varenicline with supportModerate Bupropion with supportModerate Nortriptyline with supportModerate Cytisine with supportModerate 22 1 Bought ‘over the counter’ without professional support

Effectiveness How many smokers who take the medicine stop smoking as a result? Often expressed as the ‘number needed to treat’ (NNT) If a medicine helps 10% of smokers to stop for at least 6 months, NNT=10 Levels: –High: NNT no more than 10 –Moderate: NNT between 10 and 20 –Low: NNT more than 20 23

Efficacy in randomised controlled trials 24 Stead et al 2008, Cahill et al 2012, Cochrane Single NRT: N=51,265 Dual NRT: 4,664 NRT for ‘reduce to quit’: N=3,429 Pre-treat with NRT patch: N=424 Hughes et al 2008, Cahill et al 2012, Cochrane Varenicline: N=6,166 Bupropion: 11,440 Nortripyline: N=975 Cytisine: N=937 Bars represent 95% confidence intervals from meta-analyses

‘Real-world’ effectiveness studies Required to assess effectiveness rather than just efficacy Can assess implementation issues Can discover small but important differences 25

26 Relative success rate in England by method of stopping Significantly better than no aid adjusting for confounding variables, p<0.001 Kotz et al (2013) Addiction, In Press

Relative effectiveness with specialist support 27 Brose et al, 2011 Thorax

Comparison between varenicline and NRT without specialist support 28 Results are similar after adjusting for potential confounding factors Kotz et al (2013) Psychopharm, Epub ahead of print

Effectiveness of current medicines InterventionPracticability NRT OTC 1 Low NRT for smoking reductionLow Single form NRT with supportModerate Dual form NRT with supportHigh Pre-treated NRT patch with supportHigh Varenicline with supportHigh Bupropion with supportModerate Nortriptyline with supportModerate Cytisine with supportModerate 29 1 Bought ‘over the counter’ without professional support

Acceptability Attractiveness to those who could benefit from it Levels: –High: More than 25% of eligible smokers use it –Moderate: 10-25% of eligible smokers use it –Low: Fewer than 10% of eligible smokers use it 30

Usage in England 31 Data from Smoking Toolkit Study N=13,457, Base: 1 smokers who tried to stop in the past year; 2 current smokers

Acceptability of current medicines InterventionPracticability NRT OTC 1 High NRT for smoking reductionModerate Single form NRT with supportModerate Dual form NRT with supportLow Pre-treated NRT patch with supportLow Varenicline with supportLow Bupropion with supportLow Nortriptyline with supportUnknown Cytisine with supportUnknown 32 1 Bought ‘over the counter’ without professional support

Safety Safety refers to the likelihood of suffering a serious adverse event attributable to the medication that results in lasting harm Levels: –High: No evidence of significant harm –Moderate: Evidence of harm but outweighed by benefit –Low: Evidence of harm not outweighed by benefit 33

Safety NRTminor adverse events depend on form used no increased risk of serious adverse events low addictive potential Vareniclinemain adverse events: nausea, disturbed dreams mixed findings on CVD risk; no clear evidence of other serious adverse events no addictive potential Bupropionmain adverse event: sleep disturbance very rare serious adverse events: seizures, allergic reaction no addictive potential Nortriptylinemain adverse events: dry mouth, drowsiness can cause cardiovascular and neurological damage in overdose no addictive potential Cytisineno serious adverse events reported main adverse event: nausea no addictive potential 34

Safety of current medicines InterventionPracticability NRT OTC 1 High NRT for smoking reductionHigh Single form NRT with supportHigh Dual form NRT with supportHigh Pre-treated NRT patch with supportHigh Varenicline with supportHigh Bupropion with supportHigh Nortriptyline with supportHigh Cytisine with supportHigh 35 1 Bought ‘over the counter’ without professional support

Equity Equity refers to how far an intervention reduces or increases social, economic or health disparities Levels: –High: Reduces disparities –Moderate: No effect –Low: Increases disparities 36

Equity in current treatments InterventionPracticability NRT OTC 1 Low NRT for smoking reductionLow Single form NRT with supportHigh Dual form NRT with supportHigh Pre-treated NRT patch with supportHigh Varenicline with supportHigh Bupropion with supportHigh Nortriptyline with supportHigh Cytisine with supportHigh 37 1 Bought ‘over the counter’ without professional support

Conclusions Behavioural support is via websites, written materials and text messaging can be effective; smartphone apps yet to be adequately tested All available pharmacotherapies are safe The most effective pharmacotherapy options are varenicline or dual form NRT with some professional support The most acceptable is NRT bought over the counter but it has low effectiveness possibly due to poor adherence For the future, cytisine offers the prospect for an affordable, acceptable, practicable and effective pharmacotherapy 38