Investigating factors which moderate the effectiveness of varenicline in clients using smoking cessation services in England Dr Neil Walker – Statistician, Oxford Biomedical Research Centre Hayley Robinson – Locality Lead, Quit51 Stop Smoking Service

Overview Stop Smoking Services in England and pharmacotherapy Varenicline v Nicotine Replacement Therapy (NRT); results from Randomised Control Trials (RCTs) Research Question (treatment moderators) Data and Analysis Results and Conclusions

Stop Smoking Services in England Remit – Provide a programme of support to smokers wishing to quit according to National Centre for Smoking Cessation and Training (NCSCT) guidelines Service Details: Quit date agreed Emphasis on complete cessation 12 sessions over 12 weeks with accredited adviser Pharmacotherapy provided Pharmacotherapy – Nicotine Replacement Therapy (NRT), Varenicline (Champix), Bupropion (Zyban)

NRT v Varenicline NRT Delivers nicotine cigarette free Combination use Most common treatment in SSS Varenicline Nicotine receptor partial agonist Tablets x 2 a day Adverse effects in some cases

RCTs Research into efficacy of different smoking cessation treatments: McNeill et al, 2010 (literature review) – varenicline > bupropion > NRT > placebo Cahill et al, 2011 (meta-analysis) – varenicline > bupropion = (single) NRT > placebo Results from various RCTs consistently demonstrate varenicline is associated with higher quit rate than NRT and other treatments But… RCTs carried out under artificial conditions which may not hold in “real world” Observational data analysis less common – but examples exist (e.g. Sicras-Mainar et al, 2011)

Research Questions Use observational smoking cessation data to assess real-world impact of current treatments. Specifically: Varenicline v NRT Whether such an effect is attenuated by other covariates (age, sex…) Address question 2 by fitting interactions in statistical models

Data Quit51 – Accredited smoking cessation service (NCSCT) Data on clients using service (quit date) from 15 March 2013 to 16 March 2016 Recorded from 11 regions (West Cheshire, East Sussex, Leicestershire, Lincolnshire, Sandwell, Solihull, Stoke, Surrey, Telford & Wrekin, Walsall and Worcestershire) Detailed information on: Personal & demographic information Individual programme (group sessions/one to one, pharmacotherapy etc.) Sessions attended Quit success/failure at various time points: self-reporting, Carbon Monoxide (CO) validation (4 weeks) And much else besides…

Data Restrictions applied pre-analysis Used first records only (some clients registered more than once) Omitted cases where (i) no treatment recorded (ii) more than one treatment recorded (iii) bupropion recorded as treatment and where the recorded age was unrealistic (<13 or >90) and where quit date post 31 Jan 2016 and pregnant women Original data, N=22472. After restrictions, N=8594. NRT; n=6304 (73.3%), varenicline; n=2290 (26.6%)

Explanatory variables Treatment (varenicline/NRT) Gender Age (13-19, 20-39, 40-59, 60-90) Service taken up (one-to-one, GP practice, pharmacy, other [other = drop-in, telephone service, pharmacy]) Year (2013, 2014, 2015, 2016) Yearly quarter (1=Jan-Mar, 2=Apr-Jun, 3=Jul-Sep, 4=Oct- Dec) Nicotine dependence (Fagerstrom score 0-10, higher score indicates greater dependence) Deprivation (The English Index of Multiple Deprivation [IMD], mapped to GP postcode; 1-10, lower score indicates greater deprivation)

Analysis Generalised Linear Mixed Model (GLMM) Y = CO validated quit (4 weeks) (0/1) – 1 = success, 0 = failed or lost to system Bernoulli distribution Logit link X = treatment*gender + treatment*age + treatment*service + treatment*year + treatment*quarter + treatment*dependence + treatment*deprivation Random effect = region Backwards stepwise (𝛼=0.05) “optimal model”

Summary Stats (Gender + Age)

Summary Stats (Treatment + Service)

Summary Stats (Year + Quarter)

Summary Stats (Dependence + Deprivation) Fagerstrom score Deprivation index

Optimal Model All main effects + treatment*service + treatment*dependence (all other interactions discarded) Variable   n/N (%) Β (logit) OR (95% CI) Wald-statistic (d.f.) p-value Gender 5.9 (1) 0.02 Male 2152/4093 (52.6%) 1 (-) Female 2229/4501 (49.5%) -0.11 0.90 (0.82-0.98) Age 68.3 (3) <0.001 13-19 210/256 (37.8%) 20-39 1410/2900 (48.6%) +0.42 1.52 (1.24-1.86) 40-59 1846/3533 (52.3%) +0.60 1.82 (1.48-2.23) 60+ 915/1605 (57.0%) +0.81 2.25 (1.81-2.80) Treatment NA NRT 2908/6304 (46.1%) varenicline 1473/2290 (64.3%) +0.97 2.64 (2.29-3.04) Service Year 18.1 (3) Quarter 16.6 (3) Fagerstrom -0.065 0.94 (0.92-0.96) Deprivation +0.042 1.04 (1.02-1.06) 17.7 (1)

Model results (interactions) Variable   n/N (%) Β (logit) OR (95% CI) Wald-statistic (d.f.) p-value Treatment*Service 23.8 (3) <0.001 NRT*one-to-one 1496/3173 (47.1%) 1 (-) NRT*GP practice 417/1068 (39.0%) NRT*pharmacy 835/1661 (50.3%) NRT*other 160/402 (39.8%) varenicline *on-to-one 997/1411 (70.7%) varenicline *GP practice 314/594 (52.9%) -0.40 0.67 (0.52-0.86) varenicline *pharmacy 156/270 (57.8%) -0.65 0.52 (0.39-0.71) varenicline *other 6/15 (40%) -0.98 0.38 (0.12-1.16) Treatment*Fagerstrom 11.0 (1) NRT*Fagerstrom varenicline *Fagerstrom -0.082 0.92 (0.88-0.97)

Data (treatment*service)

Data (treatment*dependence)

Conclusions Real world evidence both available pharmacotherapy treatments are effective as an aid to quitting, varenicline more so than NRT. The performance of both treatments is seen to be modified by type of counselling and a client’s nicotine dependence. Quit rates can be optimised by taking these factors into account when assigning a treatment to smoking cessation clients

References McNeil JJ, Piccenna L, Ioannides-Demos LL. Smoking cessation-recent advances. Cardiovasc Drugs Ther. 2010;24(4):359-67 Cahill K, Stevens S, Perera R, Lancaster T. Pharmacological interventions for smoking cessation; an overview and network meta-analysis. Cochrane Database of Systematic Reviews. 2011; 9. DOI: 10.1002/14651858.CD009329 Sicras Mainar A, Navarro Artieda R, Diaz Cerezo S, Marti Sanchez B, Sanz De Burgoa V. Abstinence rates with varenicline compared to bupropion and nicotine replacement therapy for quitting smoking in primary care. Aten Primaria. 2011;43(9):482-9 NCSCT. National Centre for Smoking Cessation and Training 2015 [accessed 6 November 2015]. Available from: http://www.ncsct.co.uk/index.php Department for communities and local government. The English Index of Multiple Deprivation (IMD) 2015 – Guidance. Retrieved 03/06/2016; https://www.gov.uk/government/uploads/system/uploads/attachment_data/f ile/464430/English_Index_of_Multiple_Deprivation_2015_-_Guidance.pdf