1. 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

2. 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

3. 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)

4. 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

5. 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)

6. 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

7. 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…

8. 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= After restrictions, N=8594.
NRT; n=6304 (73.3%), varenicline; n=2290 (26.6%)

9. 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)

10. 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”

11. Summary Stats (Gender + Age)

12. Summary Stats (Treatment + Service)

13. Summary Stats (Year + Quarter)

14. Summary Stats (Dependence + Deprivation)
Fagerstrom score
Deprivation index

15. 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 ( )
Age
68.3 (3)
<0.001
13-19
210/256 (37.8%)
20-39
1410/2900 (48.6%)
+0.42
1.52 ( )
40-59
1846/3533 (52.3%)
+0.60
1.82 ( )
60+
915/1605 (57.0%)
+0.81
2.25 ( )
Treatment NA
NRT
2908/6304 (46.1%)
varenicline
1473/2290 (64.3%)
+0.97
2.64 ( )
Service
Year
18.1 (3)
Quarter
16.6 (3)
Fagerstrom
-0.065
0.94 ( )
Deprivation
+0.042
1.04 ( )
17.7 (1)

16. 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 ( )
varenicline *pharmacy
156/270 (57.8%)
-0.65
0.52 ( )
varenicline *other
6/15 (40%)
-0.98
0.38 ( )
Treatment*Fagerstrom
11.0 (1)
NRT*Fagerstrom
varenicline *Fagerstrom
-0.082
0.92 ( )

17. Data (treatment*service)

18. Data (treatment*dependence)

19. 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

20. 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: / 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:
Department for communities and local government. The English Index of Multiple Deprivation (IMD) 2015 – Guidance. Retrieved 03/06/2016; ile/464430/English_Index_of_Multiple_Deprivation_2015_-_Guidance.pdf