Robert West University College London London March 2008 The clinical significance and assessment of smoking cessation treatments Robert West University College London London March 2008

The importance of each quit attempt After the age of 40, each year that stopping is delayed loses an average of 3 months of life (Doll et al 2004) It is likely to be an average of at least a year before the next quit serious attempt Therefore, failing at the current quit attempt probably loses an average of 3 months of life Therefore each serious quit attempt is a precious resource that should be given the maximum possible chance of success Increasing that chance by even a small amount is clinically meaningful

Cost-effectiveness Treatments that aid cessation have the potential to be extremely cost effective in saving lives Even those that increase long-term success of an attempt by 1% (e.g. from 5% to 6%) represent cost-effective clinical interventions at a cost of 150 euros per smoker (West, 2007)

The need for rigorous assessment It is essential to evaluate treatments using the most rigorous possible methods: To know whether the typically small effects found are reliable To avoid the financial and opportunity cost of failed quit attempts using ineffective methods To enable smokers to distinguish between genuinely helpful treatments and ones that are promoted by commercial companies selling ‘snake oil’

Assessment of ‘efficacy’ This normally involves: Using continuous abstinence for at least 6 months from an appropriate point after the quit date as the primary outcome measure Intention to treat analysis with those lost to follow-up counted as continuing smokers Biochemical verification of claims of abstinence Assessment of smoking status blind to experimental condition These and other criteria are embodied in the ‘Russell Standard’ (West et al, 2005)

Assessment of effectiveness Efficacy does not necessarily translate into ‘effectiveness’ in routine clinical practice Need to examine quit rates in routine clinical practice and in population studies Compare quit rates in prospective studies in those using and not using treatments adjusting for prognostic indicators

Effectiveness of existing interventions Professional behavioural support, nicotine replacement therapies, bupropion, nortriptyline and varenicline all have proven effectiveness and can help 4% to 16% of users to achieve 6 months of continuous abstinence in a given quit attempt; this translates into 2% to 8% permanent cessation

Face-to-face individual support: Efficacy Using only studies with ≥6 months’ continuous abstinence and biochemical verification

Group support: efficacy Using only studies with ≥6 months’ continuous abstinence and biochemical verification

Effect of telephone counselling Cochrane review: ≥6 month cessation not biochemically validated

Effect of tailored internet support Not biochemically verified

Effect of NRT Cochrane: LI: Low intensity behavioural support; HI: High intensity behavioural support RTS: Reduce To Stop; Combination: various combinations versus single NRT types; Population: NRT versus no NRT in population samples without behavioural support (ATTEMPT – cohort study, not RCT)

Effect of nortriptyline, bupropion and varenicline For bupropion and nortriptyline data from Cochrane: ≥6 months’ continuous abstinence and biochemical verification; varenicline 6 month continuous abstinence data from JAMA 2006; blue shading shows effect on 12 month continuous abstinence rates of further 12w varenicline vs placebo in smokers abstinence at 12w

Face-to-face individual support plus medication: effectiveness Evaluation of the NHS stop smoking services: 12-month continuous abstinence rates of 15% accords with what would be expected from trials Specialist support in groups more effective than individual support NHS stop smoking services with varenicline 60% 4-week success rates versus 50% with NRT and bupropion Pragmatic trial of individual support in primary care failed to find effect (Aveyard et al, 2007)

Conclusions Clinical interventions to aid smoking cessation can be very cost effective ways of preventing premature death even when the effect sizes are small It is very important to apply rigorous evaluation to these methods to get the best estimates of efficacy and effectiveness This usually involves at least 6-month follow-up, intention to treat analysis and biochemical verification Gold standard treatment is multi-session behavioural support provided by specialist plus medication – probably varenicline or optimal use of NRT Telephone support and internet-based support also look to be effective