‘Cut down to quit’ with nicotine
replacement therapies in smoking
cessation: a systematic review of
effectiveness and economic analysis
D Wang,1M Connock,1P Barton,2A Fry-Smith,1
P Aveyard3and D Moore1*
1 Department of Public Health and Epidemiology, University of
2 Health Economics Facility, Health Services Management Centre,
University of Birmingham, UK
3 Department of Primary Care and General Practice, University of
* Corresponding author
Health Technology Assessment
NHS R&D HTA Programme
Health Technology Assessment 2008; Vol. 12: No. 2
‘Cut down to quit’ with nicotine replacement therapies
in smoking cessation
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Approximately 25% of adults in the UK are
smokers. Smoking is associated with numerous
diseases, including cancer and heart disease, and
smokers have reduced life expectancy. Nicotine in
cigarettes renders them addictive so that smokers
generally find it extremely difficult to give up their
habit. Most smokers (around 70%) say they would
like to stop but some express an unwillingness or
inability to do so in the near future. Nicotine
replacement therapy (NRT) attempts to substitute
the nicotine obtained from smoking with that
derived from gum, inhaler or patch, so that
smokers are enabled to quit smoking and then
gradually become independent of nicotine.
Some nicotine replacement therapies that were
previously licensed in the UK for abrupt quitting
from smoking have recently been granted a new
licensed indication called ‘cut down to stop’ or ‘cut
down to quit’ (CDTQ). This aims at smokers who
express unwillingness or inability to stop smoking
in the short term by enabling them gradually to
cut down their smoking over an extended period
while supported by NRT so that they may
eventually become able and willing to attempt to
quit altogether. Thus the CDTQ stratagem
involves more prolonged support with NRT than
the previously licensed indication for an abrupt
quit attempt and by definition targets a different
population of smokers.
The primary objective of this assessment report
was to examine the effectiveness and cost-
effectiveness of NRT for CDTQ smoking.
Searches of bibliographic databases and contact
with experts and industry were undertaken in
order to identify relevant systematic reviews,
randomised controlled trials (RCTs) and existing
economic analyses of CDTQ. Searches were
carried out in July 2006. Evidence from RCTs was
included in the report if the population consisted
of smokers who declared an inability or
unwillingness to attempt to quit smoking in the
short term, if the intervention encompassed a cut-
down smoking programme supported by NRT and
if the comparator was a cut-down programme with
placebo or other support.
Systematic reviews were included if at least one
electronic database had been searched and if RCTs
documenting quit rates in smoking reduction
programmes with NRT were reviewed. Economic
studies were included if they encompassed cost-
effectiveness or cost–utility analysis of CDTQ
A systematic review of RCTs was performed that
included meta-analyses of smoking outcomes and
analyses of individual patient data.
The outcome taken as an indicator of success was
the proportion of smokers who sustained
continuous abstinence from smoking. Various
measures for this outcome have been used, and
these encompass different durations of continuous
abstinence. The measures reviewed were:
(1) a defined period of sustained abstinence that
starts within the first 6 weeks of NRT treatment
(the measure used in most RCTs); and (2) at least
6 months’ continuous abstinence that starts at any
time within the NRT treatment period (a measure
that can be calculated from individual patient data
in the RCTs).
A decision analytical model was constructed to
estimate the cost-effectiveness of CDTQ from the
NHS perspective. CDTQ was considered as a
choice option for individual smokers and also as a
No systematic reviews of the effectiveness of
CDTQ were identified. No RCTs specifically
addressing CDTQ were identified. Seven
randomised placebo-controlled trials satisfied the
inclusion criteria; six of these were industry
sponsored. The RCTs were primarily designed
to investigate the effectiveness of a smoking
Executive summary: ‘Cut down to quit’ with nicotine replacement therapies in smoking cessation
reduction programme. Sustained smoking
cessation was only reported as a secondary
outcome in these trials and required
commencement of cessation within the first
6 weeks of treatment.
In four RCTs smokers received NRT gum or
placebo, in two NRT inhalator or placebo and in
one placebo-controlled RCT smokers exercised
free choice of the type of NRT they received.
Meta-analyses of the study level results for
sustained abstinence from smoking, point
prevalence of smoking abstinence, sustained
smoking reduction and point prevalence of
smoking reduction demonstrated statistically
significant superiority of NRT compared with
placebo for all four outcomes. The proportion of
participants who achieved sustained abstinence
commencing within the first 6 weeks of treatment
was meagre (about 2% of those in receipt of NRT).
This is not surprising given that it is inherently
unlikely that smokers who had expressed
unwillingness or inability to quit in the short term
would stop within 6 weeks. Therefore, individual
patient data from unpublished reports of five
RCTs were used to calculate sustained abstinence
of at least 6 months starting at any time
during the treatment period (generally 12
months). Using this more realistic criterion for
sustained abstinence, meta-analysis indicated
statistically significant superiority of NRT versus
placebo [relative risk 2.06, 95% confidence
interval (CI) 1.34 to 3.15]. The proportions
achieving this outcome across all five RCTs
were 6.75% (95% CI 5.3 to 8.56%) of participants
in receipt of NRT and 3.29% (95% CI 2.56
to 4.21%) of those receiving placebo. The
number-needed-to-treat was 29. This measure of
sustained abstinence was used for economic
No significant treatment-related adverse events
were reported in the trials and minor events were
similar in frequency and type to those in
previously reported studies of NRT. None of the
included studies reported health-related quality of
life measures for abstainers from smoking.
No existing economic analyses of CDTQ were
identified. A de novo decision analytic model was
constructed to estimate the cost-effectiveness of
making CDTQ with NRT available for smokers
unwilling or unable to attempt an abrupt quit.
The outcome measure was expected quality-
adjusted life-years (QALYs). The model also took
account of the possibility that some smokers
willing to attempt abrupt quitting might instead
switch to CDTQ. Smokers leaking from abrupt
quit to CDTQ were assumed either to experience
a ‘CDTQ-success rate’ or to retain the abstinence
success rate of abrupt quitters.
The model compared three CDTQ NRT options
(over-the-counter NRT; brief advice + NRT
repeat prescriptions; smokers’ clinic with
individual or group counselling + repeat NRT
prescriptions) with no quit attempt, attempt
without NRT, abrupt quit attempt with NRT in
any of three options (over-the-counter NRT;
brief advice + NRT repeat prescriptions; smokers’
clinic with individual or group counselling
+ NRT repeat prescriptions). A smoker may thus
switch to any one of three CDTQ modes from any
of five other behaviours (no quit attempt, quit
attempt without NRT, abrupt quit attempt with
NRT in any of three available modes). Further
analyses compared each CDTQ option with a mix
of no quit attempt and corresponding abrupt quit
option. Lastly, a ‘full analysis’ compared a range of
CDTQ options with the full mix of non-CDTQ
CDTQ success rate was based on trials in which
behavioural support was variously described as
minimal or moderate (at least eight scheduled
clinic visits). In a real-world setting this
corresponds more closely to ‘smokers’ clinic’ than
to ‘brief advice plus repeat prescription’.
Model results suggest that CDTQ with NRT
delivers incremental cost-effectiveness ratios
(ICERs) ranging from approximately £1500/QALY
to approximately £7700/QALY depending on the
age at which smoking cessation was achieved and
the modes of CDTQ delivery.
Assuming applicability to a single population,
CDTQ was not cost-effective compared with
If CDTQ with NRT were to be offered on the
NHS as a matter of policy, the base-case results
suggest that it would only be effective and cost-
effective if a substantial majority of the people
attempting CDTQ with NRT were those who
would otherwise make no attempt to quit. This
result is robust to considerable variation in the
forms of CDTQ with NRT offered, and to the
assumptions about QALY gained per quit success.
However, incremental cost-effectiveness ratio
values are sensitive to assumptions about success
Health Technology Assessment 2008; Vol. 12: No. 2 (Executive summary)
rates for different methods of attempting to quit
smoking. The base case assumes that willing
abrupt quitters who switch to CDTQ have the
same success rate in CDTQ as smokers who are
unwilling to try abrupt quit. If it is assumed that
smokers who might otherwise try abrupt quitting
and undertake CDTQ instead retain a fixed
success rate (i.e. the same success rate in CDTQ as
in abrupt quit), then all forms of CDTQ provision
appear to be cost-effective. This assumes that
success rate is more strongly related to
characteristics of smokers than to the particular
nature of the NRT intervention.
Meta-analysis of RCT evidence of quit rates in
NRT-supported smoking reduction studies
indicates that NRT is an effective intervention in
achieving sustained smoking abstinence for
smokers who declare unwillingness or inability to
attempt an abrupt quit. The 12-month sustained
abstinence success rate in this population
(approximately 5.3% with NRT versus
approximately 2.6% with placebo) is considerably
less than that documented for an abrupt quit NRT
regime in smokers willing to attempt an abrupt
quit with NRT (which according to other
systematic reviews is approximately 16% with NRT
versus 10% with placebo).
Most of the evidence of effectiveness of CDTQ in
this report came from trials that required
considerable patient–investigator contact.
Therefore, for CDTQ with NRT to generate
similar abstinence rates for this recalcitrant
population in a real-world setting would probably
require a similar mode of delivery.
Decision analytic modelling based on reasonable
assumptions about costs, benefits and success rates
suggests that CDTQ is highly cost-effective
compared with no quit attempt. CDTQ remains
cost-effective if dilution from abrupt quitting
forms a small proportion of CDTQ attempts. In
an alternative analysis in which smokers who
switch from an abrupt quit to CDTQ retain the
success rate of abrupt quitters, all forms of CDTQ
Recommendations for further
Randomised trials in recalcitrant smokers allowing
head-to-head comparison of CDTQ delivered with
various NRT modalities (e.g. inhalator, nasal
spray, lozenge, gum, patch) would be informative.
Research is also needed into the best ways of
implementing a CDTQ strategy and integrating
this with abrupt quit options in the context of all
UK smoking services.
Wang D, Connock M, Barton P, Fry-Smith A,
Aveyard P, Moore D. ‘Cut down to quit’ with
nicotine replacement therapies in smoking
cessation: a systematic review of effectiveness and
economic analysis. Health Technol Assess 2008;12(2).
Executive summary: ‘Cut down to quit’ with nicotine replacement therapies in smoking cessation
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