‘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
How to obtain copies of this and other HTA Programme reports.
An electronic version of this publication, in Adobe Acrobat format, is available for downloading free of
charge for personal use from the HTA website (http://www.hta.ac.uk). A fully searchable CD-ROM is
also available (see below).
Printed copies of HTA monographs cost £20 each (post and packing free in the UK) to both public and
private sector purchasers from our Despatch Agents.
Non-UK purchasers will have to pay a small fee for post and packing. For European countries the cost is
£2 per monograph and for the rest of the world £3 per monograph.
You can order HTA monographs from our Despatch Agents:
– fax (with credit card or official purchase order)
– post (with credit card or official purchase order or cheque)
– phone during office hours (credit card only).
Additionally the HTA website allows you either to pay securely by credit card or to print out your
order and then post or fax it.
Contact details are as follows:
c/o Direct Mail Works Ltd
4 Oakwood Business Centre
Downley, HAVANT PO9 2NP , UK
NHS libraries can subscribe free of charge. Public libraries can subscribe at a very reduced cost of
£100 for each volume (normally comprising 30–40 titles). The commercial subscription rate is £300
per volume. Please see our website for details. Subscriptions can only be purchased for the current or
Tel: 02392 492 000
Fax: 02392 478 555
Fax from outside the UK: +44 2392 478 555
Paying by cheque
If you pay by cheque, the cheque must be in pounds sterling, made payable to Direct Mail Works Ltd
and drawn on a bank with a UK address.
Paying by credit card
The following cards are accepted by phone, fax, post or via the website ordering pages: Delta, Eurocard,
Mastercard, Solo, Switch and Visa. We advise against sending credit card details in a plain email.
Paying by official purchase order
You can post or fax these, but they must be from public bodies (i.e. NHS or universities) within the UK.
We cannot at present accept purchase orders from commercial companies or from outside the UK.
How do I get a copy of HTA on CD?
Please use the form on the HTA website (www.hta.ac.uk/htacd.htm). Or contact Direct Mail Works (see
contact details above) by email, post, fax or phone. HTA on CD is currently free of charge worldwide.
The website also provides information about the HTA Programme and lists the membership of the various
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
NIHR Health Technology Assessment Programme Download full-text
effectiveness, costs and broader impact of health technologies for those who use, manage and provide
care in the NHS. ‘Health technologies’ are broadly defined as all interventions used to promote health,
prevent and treat disease, and improve rehabilitation and long-term care.
The research findings from the HTA Programme directly influence decision-making bodies such as the
National Institute for Health and Clinical Excellence (NICE) and the National Screening Committee
(NSC). HTA findings also help to improve the quality of clinical practice in the NHS indirectly in that
they form a key component of the ‘National Knowledge Service’.
The HTA Programme is needs-led in that it fills gaps in the evidence needed by the NHS. There are
three routes to the start of projects.
First is the commissioned route. Suggestions for research are actively sought from people working in the
NHS, the public and consumer groups and professional bodies such as royal colleges and NHS trusts.
These suggestions are carefully prioritised by panels of independent experts (including NHS service
users). The HTA Programme then commissions the research by competitive tender.
Secondly, the HTA Programme provides grants for clinical trials for researchers who identify research
questions. These are assessed for importance to patients and the NHS, and scientific rigour.
Thirdly, through its Technology Assessment Report (TAR) call-off contract, the HTA Programme
commissions bespoke reports, principally for NICE, but also for other policy-makers. TARs bring
together evidence on the value of specific technologies.
Some HTA research projects, including TARs, may take only months, others need several years. They can
cost from as little as £40,000 to over £1 million, and may involve synthesising existing evidence,
undertaking a trial, or other research collecting new data to answer a research problem.
The final reports from HTA projects are peer-reviewed by a number of independent expert referees
before publication in the widely read journal series Health Technology Assessment.
Criteria for inclusion in the HTA journal series
Reports are published in the HTA journal series if (1) they have resulted from work for the HTA
Programme, and (2) they are of a sufficiently high scientific quality as assessed by the referees and editors.
Reviews in Health Technology Assessment are termed ‘systematic’ when the account of the search,
appraisal and synthesis methods (to minimise biases and random errors) would, in theory, permit the
replication of the review by others.
he Health Technology Assessment (HTA) Programme, part of the National Institute for Health
Research (NIHR), was set up in 1993. It produces high-quality research information on the
The research reported in this issue of the journal was commissioned by the HTA Programme as project
number 06/09/01. The contractual start date was in May 2006. The draft report began editorial review in
March 2007 and was accepted for publication in June 2007. As the funder, by devising a commissioning
brief, the HTA Programme specified the research question and study design. The authors have been
wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The
HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to
thank the referees for their constructive comments on the draft document. However, they do not accept
liability for damages or losses arising from material published in this report.
The views expressed in this publication are those of the authors and not necessarily those of the
HTA Programme or the Department of Health.
Professor Tom Walley
Dr Aileen Clarke, Dr Peter Davidson, Dr Chris Hyde,
Dr John Powell, Dr Rob Riemsma and Professor Ken Stein
Sarah Llewellyn Lloyd, Stephen Lemon, Kate Rodger,
Stephanie Russell and Pauline Swinburne
© Queen’s Printer and Controller of HMSO 2008
This monograph may be freely reproduced for the purposes of private research and study and may be included in professional journals provided
that suitable acknowledgement is made and the reproduction is not associated with any form of advertising.
Applications for commercial reproduction should be addressed to: NCCHTA, Mailpoint 728, Boldrewood, University of Southampton,
Southampton, SO16 7PX, UK.
Published by Gray Publishing, Tunbridge Wells, Kent, on behalf of NCCHTA.
Printed on acid-free paper in the UK by St Edmundsbury Press Ltd, Bury St Edmunds, Suffolk.