9 The evidence

This section lists the evidence statements from 5 reviews provided by external contractors (see What evidence is the guidance based on?) and links them to the relevant recommendations. (See Summary of the methods used to develop this guidance for the key to quality assessments.)

This section also links the recommendations to the expert papers and sets out a brief summary of findings from the economic analysis and the fieldwork.

The evidence statements are short summaries of evidence, in a review, report or paper (provided by an expert in the topic area). Each statement has a short code indicating which document the evidence has come from. The letter(s) in the code refer to the type of document the statement is from, and the numbers refer to the document number, and the number of the evidence statement in the document.

Evidence statement 1.1a indicates that the linked statement is numbered 1a in review 1 'Safety, risks and pharmacokinetics profiles of tobacco harm reduction technologies'. Evidence statement 2.4.1 indicates that the linked statement is numbered 4.1 in review 2 'The effectiveness of tobacco harm reduction approaches with the intention of quitting (that is, cutting down to quit or reduction to stop smoking), with and without assistance'. Evidence statement 3.1.5 indicates that the linked statement is numbered 1.5 in review 3 'The effectiveness of long-term harm reduction approaches without the prior intention of quitting'. Evidence statement 4.1.37 indicates that the linked statement is numbered 1.37 in review 4 'Barriers and facilitators to implementing tobacco harm reduction approaches (including user and provider perspectives)'. Evidence statement 5.1 indicates that the linked statement is numbered 1 in review 5 'Long term use of non-tobacco nicotine containing products in individuals who have quit smoking abruptly'.

The reviews, expert papers, economic analysis and fieldwork report are available online.

Recommendation 1: evidence statements 1.1a, 1.1b, 1.1c, 1.2a, 1.2b, 1.3a, 1.3c, 1.4a, 1.4b, 1.4c, 1.5, 1.7, 1.8, 1.9, 2.3.1, 3.3.1, 3.8.3, 4.1.5, 4.1.17, 4.1.18, 4.1.37, 4.1.42, 5.4, 5.5, 5.6; expert papers 1, 2, 8a, 8b

Recommendation 2: evidence statements 4.1.4, 4.1.10, 4.1.11, 4.1.15, 4.1.17, 4.1.18

Recommendation 3: evidence statements 2.1, 2.1.1, 2.1.2, 3.1.1, 3.1.2, 3.1.3, 3.1.5, 5.1, 5.2, 5.3; expert paper 2

Recommendation 4: evidence statements 2.4, 2.4.1, 2.4.2, 2.4.3, 2.5, 2.5.1, 2.5.2, 2.6, 2.6.1, 2.6.2, 3.4.1, 3.4.2, 3.4.3, 3.4.4, 3.4.5, 3.4.6, 3.4.7, 3.6.1, 3.6.2, 3.8.2, 4.1.15; IDE

Recommendation 5: evidence statements 2.1, 2.1.1, 2.1.2, 3.1.1, 3.1.2, 3.1.3, 3.1.5, 3.1.6, 3.8.1, 3.8.2

Recommendation 6: evidence statements 1.1a, 1.1b, 1.1c, 1.3a, 1.3c, 1.4b, 1.7, 2.1, 2.1.1, 2.1.2, 3.8.1, 3.8.2, 4.1.37, 4.1.42; expert paper 2

Recommendation 7: IDE

Recommendation 8: evidence statement 3.4.8; expert paper 2

Recommendation 9: evidence statement 4.1.7; expert papers 5, 6

Recommendation 10: evidence statements 4.1.7, 4.2.6; expert papers 5, 6

Recommendation 11: evidence statements 5.1, 5.2, 5.3, 5.4, 5.5

Recommendation 12: IDE

Recommendation 13: IDE

Recommendation 14: evidence statement 1.3c; IDE

Evidence statements

Please note that the wording of some evidence statements has been altered slightly from those in the evidence review(s) to make them more consistent with each other and NICE's standard house style.

Evidence statement 1.1a Risks and adverse events associated with nicotine replacement and nicotine containing products: primary studies

Evidence from 10 randomised controlled trials (4 [++]1–4 and 6 [+]5–10) strongly suggests that adverse events are common when nicotine replacement therapy (NRT) is used for smoking harm reduction, but these tend to be mild or moderate and are rarely severe. No authors have attributed serious adverse events to NRT when used as part of smoking harm reduction. NRT is generally well tolerated when used in this setting. Frequently reported adverse events depend on the route of administration but include throat irritation, coughing, nausea, vertigo/dizziness, vomiting or palpitations. One study7 (+) reported no evidence of increased cardiac events in patients with existing cardiac disease treated with NRT for 18 months. The duration of use of NRT in these studies varied from 1–18 months. Follow up did not extend beyond 24 months, so the randomised trials do not provide safety data for longer-term use.

1 Bolliger et al. 2000

2 Carpenter et al. 2004

3 Etter et al. 2002

4 Rennard et al. 2006

5 Batra et al. 2005

6 Carpenter et al. 2003

7 Haustein et al. 2004

8 Joseph et al. 2008

9 Kralikova et al. 2009

10 Wennike et al. 2003

Evidence statement 1.1b Risks and adverse events associated with nicotine replacement and nicotine containing products: meta-analysis

Evidence from a meta-analysis1 (++) of 2767 participants drawn from several of the randomised trials cited above plus 2 unpublished sources corroborates the findings shown above. The unpublished trials used NRT for 9 months and 12 months. The results suggest that there is no difference between NRT (used for between 6 and 18 months) and placebo in terms of mortality, serious adverse events or discontinuation of therapy due to adverse events. But nausea occurs more frequently with active NRT (odds ratio [OR] 1.69, 95% confidence interval [CI] 1.21–2.36). Use of the meta-analysis has 2 caveats:

  • the meta-analysis re-iterates a substantial body of the same data from 6 randomised trials (3 [++]2–4 and 3 [+]5–7) cited above

  • there was substantial heterogeneity of results in the meta-analysis of serious adverse events.

1 Moore 2011

2 Batra et al. 2005

3 Bolliger et al. 2000

4 Etter et al. 2002

5 Haustein et al. 2004

6 Rennard et al. 2006

7 Wennike et al. 2003

Evidence statement 1.1c Risks and adverse events associated with nicotine replacement and nicotine containing products: cardiovascular risk markers

Evidence from 5 randomised trials (2 [++]1,2 and 3 [+]3–5) and 1 non-randomised, controlled study6 (+) suggests that there are no substantial changes in risk markers for cardiac disease in people treated with NRT as part of smoking harm reduction. The randomised controlled trial evidence is cited from a Cochrane review [++]7. Risk markers studied included white blood cell count, fibrinogen, C-reactive protein (CRP), lipids, F2-isoprostanes, 4‑(Methylnitrosamino)‑1‑(3‑pyridyl)‑1‑butanol (NNAL), 1‑hydroxypyrene (1‑HOP). One (++) study2 found favourable changes in both NRT and placebo groups. No study reported increases in risk markers for cardiovascular disease arising from NRT. Follow up did not extend beyond 24 months.

1 Bolliger et al. 2000

2 Rennard et al. 2006

3 Batra et al. 2005

4 Joseph et al. 2008

5 Kralikova et al. 2009

6 Haustein et al. 2004

7 Stead and Lancaster 2007

Evidence statement 1.2a Safety of long-term use of nicotine replacement therapy and nicotine containing products

There are no studies available of the safety of NRT used in smoking harm reduction in the long term (maximum duration of NRT use is 5 years). The strongest evidence available for the long-term safety of NRT with concurrent smoking comes from a large subgroup of patients studied in the 5-year 'Lung health study'1,2 (+) of NRT in smoking cessation, where a large patient group continued to smoke and continued to use NRT. The results of this multicentre randomised controlled trial suggest that long-term use of NRT is not associated with an increased incidence of harm, including cardiovascular events or cancer, with the latest analysis of outcome at 12.5 years from study outset.

1 Murray et al. 1996

2 Murray et al. 2009

Evidence statement 1.2b Safety of long-term use of nicotine replacement therapy and nicotine containing products: cardiac disease

Six studies (4 [+]1–4 and 1 [−]5) evaluated the safety of NRT in patients with cardiac disease and did not find any increased incidence of cardiovascular events or any other adverse events.

1 Mahmarian et al. 1997

2 Leja et al. 2007

3 Joseph et al. 2008

4 Joseph et al. 1996

5 Paciullo et al. 2009

6Tzivoni et al. 1998

Evidence statement 1.3a Risks associated with use of unlicensed nicotine containing products

All available evidence relates to electronic cigarettes (e-cigarettes). There is no evidence on the long-term safety of e-cigarettes, whether used alone or with concurrent cigarette smoking. There isn't a large volume of reliable evidence on the short-term safety of e-cigarettes. One (+) randomised crossover trial1 found that the rate of acute adverse events arising from e-cigarette use (occurring on the first day of use) were intermediate between placebo e-cigarette and licensed nicotine inhalator. A non-randomised (+) study also found no acute effect on heart rate from the use of 2 models of e-cigarette2.There are no firm cases of harm that are directly attributable to e-cigarette use. One news article in the British press3 (−) reported a death from lipoid pneumonia where e- cigarette use was implicated by a treating clinician. The inquest to the death recorded an open verdict.

1 Bullen et al. 2010

2 Vansickel et al. 2010

3 BBC, 2011

Evidence statement 1.3c Contents of e-cigarettes

There is evidence from 2 laboratory analyses (both [++])1,2 that e-cigarettes can contain nicotine derived nitrosamine contaminants and diethylene glycol, a highly toxic substance. Most e-cigarettes include propylene glycol. This chemical is generally considered to be of low toxicity although there appears to be insufficient data concerning its inhalational toxicity. A physical evaluation of e-cigarettes (+)3 found that e-cigarettes (including their constituent parts and instruction manuals) lack important information regarding contents, use and essential warnings. The same study3 found that e-cigarettes frequently leak, presenting a hazard, and that there are currently no methods for proper disposal of e-cigarettes, including cartridges.

1 Westenberger 2009

2 Medicines and Healthcare Products Regulatory Agency 2011

3 Trtchounian et al. 2011

Evidence statement 1.4a Impact of nicotine replacement therapies and nicotine containing products on the concentration of nicotine in the blood

Evidence from 6 (all [+])1–6 controlled studies suggests that nicotine concentrations with smoking alone are typically in the range 22–30 ng/ml. When NRT use is accompanied by smoking, nicotine concentrations can rise to higher levels. The highest value observed was 63.4 ng/ml when a 44 mg patch was used with ad libitum smoking (+)4. Some authors suggest that smoking behaviour self-regulates to maintain a constant nicotine concentration but evidence (particularly for patches) suggests that this is imprecise.

Despite increased nicotine concentration with concomitant use, the evidence from two studies (+)4,6 suggests there are no increases in the incidence of side effects or significant changes in physiological parameters such as blood pressure and heart rate.

1 Ebert et al. 1984

2 Fagerstrom et al. 2002

3 Foulds et al. 1992

4 Pickworth et al. 1994

5 Russell et al. 1976

6 Zevin et al. 1998

Evidence statement 1.4b Compensatory smoking

Compensatory smoking is a mechanism whereby smokers, who have reduced the number of cigarettes they smoke per day, modify their smoke intake, for example, by puffing more frequently or more intensely, and so titrate their nicotine intake1 (+). Two studies1,2 (1 [+] and 1 [−]) correlating reductions in expired carbon monoxide (CO) with reductions in the number of cigarettes per day have demonstrated that some compensation occurs, but that the reduction in CO is significant. A narrative review of studies [−]3 suggests that for acute NRT forms (gum, lozenge, inhalator, nasal spray) a reduction in CO is accompanied by little change in plasma nicotine, suggesting close titration by subjects. In contrast, the same study found for nicotine patches, plasma nicotine increased, suggesting poor titration for the transdermal route.

Three studies4,5,6 (all [+]) of snuff use and low yield cigarettes also indicate that users are able to manage their intake to achieve a plasma nicotine level of typically 35–37 ng/ml. One (+) study6 showed that users of nasal snuff can generate similar plasma nicotine levels to those generated by smoking a cigarette, in approximately equal time (10 minutes).

1 Hughes and Carpenter 2005

2 Hughes 2000

3 Fagerstrom and Hughes 2002

4 Holm et al. 1992

5 Jarvis et al. 2001

6 Russell et al. 1981

Evidence statement 1.4c Nicotine absorption routes from NRT and e-cigarettes

The routes of absorption of medicinal nicotine are buccal (lozenge, gum, microtab, inhalator), dermal (patches) and nasal mucosa (nasal spray). Notably nicotine is mainly absorbed from the inhalator via the oral mucosa, with minimal absorption via the lungs. The degree of absorption of nicotine from e-cigarettes is uncertain, 2 studies (both [−])1,2 suggest the delivery of nicotine by these devices is via buccal absorption.

1 Russell et al. 1987

2 Vansickel and Eissenberg 2012

Evidence statement 1.5 Pharmacokinetic data for each nicotine administration route

Cigarettes Evidence from a pharmacokinetic study (+) indicates that 10 minutes of cigarette smoking can generate an arterial blood Cmax of 38–40 ng/ml nicotine in Tmax 8 minutes and a venous blood Cmax of 17–19 ng/ml in a Tmax of 10–12 minutes1.

Snus Absorption of nicotine from snus is primarily through the oral mucosa and can produce a venous blood Cmax of 14–15 ng/ml in a Tmax of 30–37 minutes (+)2–4.

NRT lozenge/tablet These products dissolve in the mouth (and are not intended to be swallowed) and absorption of nicotine is primarily through the oral mucosa. A single dose of between 1 and 6 mg nicotine that is allowed to dissolve in the mouth can generate a Cmax of 2–9 ng/ml in Tmax of 10–90 minutes (+)3,5–8. Multiple, sequential doses do not appear to result in a Cmax higher than 30 ng/ml (+)9–13.

NRT gum NRT gum is chewed in the mouth. Absorption of nicotine is primarily through the oral mucosa. When 2–4 mg nicotine or less is administered as gum and chewed for 20–30 minutes, a Cmax of 3–15 ng/ml is reached in Tmax of 20–56 minutes (+)2,3,5,8,11,14. Larger, sequential doses of 24–48 mg, chewed for 30 minutes each hour over 12 hours, result in a Cmax of 11–30 ng/ml in a Tmax of 28–30 minutes (+)9,10,13.

NRT nasal spray The absorption route for nasal spray is primarily through the nasal mucosa. A dose of 0.5–2.5 mg nicotine, given via nasal spray over 5 minutes or less, can result in Cmax of 5–23 (mean 11) ng/ml in Tmax of 5–30 (mean 12) minutes (+)15–19. Nasal spray, therefore, appears to offer potentially rapid absorption of nicotine, compared to the other NRT routes.

NRT inhalator The pharmacokinetic data on the NRT inhalator appear to support buccal absorption as the primary nicotine absorption route. 20 minutes of use appears to generate a variable Cmax of mean 23 ng/ml (range 2–34) in Tmax of 27 minutes (range 20–32 minutes) (+)20–21.

NRT patch The absorption route for nicotine patches is transdermal. Patches appear to offer slow, but sustained absorption of nicotine. Doses of 15–40 mg, given over 16–24 hours, can result in a Cmax of 19 ng/ml (range 14–26 ng/ml) in Tmax of mean 9 hours (range 6–12 hours) (+)22–25.

e-cigarettes e-cigarettes are not licensed medicines in the UK and little is known about the extent to which they deliver nicotine to the circulation. A small volume of available data suggest that a 16 mg dose given over 5 minutes can result in a Cmax of 1.3 ng/ml in Tmax of 20 minutes (+)21. Data from one study (−)26, suggest that 10 consecutive puffs at 30-second intervals, followed by 60 minutes of ab libitum use, can generate a Cmax of 16.3 ng/ml in 75 minutes.

1 Gourlay and Benowitz 1997

2 Lunell and Curvall 2011

3 Kotlyar et al. 2007

4 Foulds 2003

5 Dautzenberg 2007a

6 Molander and Lunell 2000b

7 Molander and Lunell 2000d

8 Johnson and Johnson 2011a

9 Dautzenberg 2007b

10 Dautzenberg 2007c

11 Molander and Lunell 2000a

12 Molander and Lunell 2000c

13 Johnson and Johnson 2011b

14 Shiffman 2009

15 Guthrie 1999

16 Gourlay 1997b

17 Perkins 1991

18 Lunell 1995

19 Sutherland 1992

20 Molander 1996

21 Bullen 2010

22 Veaugh-Geiss 2010

23 Gourlay 1997a

24 Lewis 2007

25 Vanakoski 1996

26 Vansickel and Eissenberg 2012

Evidence statement 1.7 Snus and cancer risk

The evidence suggests that there is a statistically significantly increased risk of some types of cancer (pancreatic, oesophageal and possibly squamous cell head and neck cancer) associated with using Swedish snus after taking account of the risk arising from concurrent smoking1–5. However, these risks from snus are substantially lower than those associated with smoking. Nicotine itself is not regarded as a carcinogen.

Compared to non-smokers, smokers are at increased risk of cancers of the lung, oesophagus, oropharyx, stomach, rectum and anus5–10.

The risk of cancers (lung, pancreatic, oral, colon, rectum and anus) in dual smoker and snus users exceeds the risk of cancer attribute to using snus alone6, 10–12.

1 Boffetta et al. 2008

2 Broadstock 2007

3 Lee and Hamling 2009a

4 SCENIHR 2008

5 Lewin et al. 1998 (cited by Broadstock et al. 2007)

6 Luo et al. 2007 (cited by Broadstock et al. 2007)

7 Lagergren et al. 2000 (cited by Broadstock et al. 2007)

8 Ye et al. 1999 (cited by Broadstock et al. 2007)

9 Roosaar et al. 2008 (cited by Broadstock et al. 2007)

10 Zendehdel et al. 2008 (cited by Broadstock et al. 2007)

11 Boffetta et al. 2005 (cited by Broadstock et al. 2007)

12 Nordenvall et al. 2011

[NB: Although Swedish snus is excluded from the scope of this guidance, the evidence was used as a proxy measure of the effects of long-term nicotine use in the absence of long-term licensed nicotine-containing product data. For further details, see appendix 10 in evidence review 1.]

Evidence statement 1.8 Snus and risk of myocardial infarction

The evidence suggests that use of Swedish snus is associated with greater likelihood of fatal myocardial infarction1–3. Duration of exposure is not consistently reported but 1 study suggested that duration of exposure was 15 years4. The evidence suggests that lengthy exposure is not associated with a change in resting blood pressure but there is experimental evidence that nicotine may affect lipid metabolism3.

Smokers are at substantially increased risk of myocardial infarction compared to non-smokers and also in comparison to non-smokers who use snus5. While former smokers currently using snus had an increased risk of acute myocardial infarction than never smokers6, the risk in current smokers who also use snus was larger5,6.

1 Broadstock 2007

2 Boffetta and Straif 2009

3 SCENIHR 2008

4 Bolinder et al. 1994 (cited by Broadstock et al. 2007)

5 Huhtasaari et al. 1999 (cited by Broadstock 2007)

6 Hergens et al. 2005 (cited by Broadstock 2007)

Evidence statement 1.9 Snus in the context of years of life lost due to tobacco

One systematic review [+]1 reports that the precise magnitude of health gain arising from choosing less harmful alternatives to smoking is difficult to quantify. It cites data from a modelling study2 which estimates the extent of harm (in years of life lost) in 4 different exposure-based groups: smokers who continue to smoke, smokers who switch to snus, smokers who quit smoking and snus users who never smoked. The model suggests that the health benefit gained (that is, by reducing the number of life years lost) for a smoker who switches to snus, but who would not otherwise have quit smoking, is substantially greater than the life years lost by a snus user who never smoked. The model suggests that the life years lost by a smoker who switches to snus are only marginally greater than the life years lost by a smoker who quits tobacco altogether. The systematic review authors conclude that the overall population effect of snus is likely to be beneficial.

NRT should be an intuitively safer option than Swedish snus because it does not contain the numerous potentially harmful constituents of snus for example, nitrosamines. In terms of NRT, a safety issue to overcome is whether through smoking with concurrent NRT, any harm is likely to result from the maximum blood concentrations of nicotine achieved and also the potentially long-term exposure to nicotine. Data from Swedish studies presented in this report appear to be based on long-term exposure (decades). The same studies do not accurately estimate the volume of nicotine taken over time from cigarettes and snus combined. Studies of efficacy may inform the PDG whether NRT use with concurrent smoking leads to a reduced volume of smoking expressed as cigarettes per day.

1 Scientific Committee on Emerging and Newly Identified Health Risks 2008

2 Gartner et al. 2007 (cited by SCENIHR 2008)

Evidence statement 2.1 (including statements 2.1.1–2.1.2) How effective are pharmacotherapies in helping people cut down smoking before quitting?

2.1 Three RCTs examined the efficacy of NRT gum (1 [++]1 and 1 [+]2)and lozenges (1 [++])3. In addition there was 1 (+) quasi-randomised controlled trial (quasi-RCT)4 and 1 (−) uncontrolled before-and-after study (UBA)5 with a combined intervention of behavioural therapy plus gum.

Two studies1,3 were deemed to be studies at low risk of bias.

2.1.1 There is moderate evidence from 2 RCTs(1 [++]3 and 1 [+])2 of no significant difference in long-term abstinence rates between gradual and abrupt cessation when using NRT (gum or lozenges) although the trend favours abrupt cessation. The CO and cotinine validated 4-week quit rate at 12 months was 16.5% for gradual compared to 24.0% for abrupt cessation, p=0.142. The OR for CO validated abstinence at 6 months (gradual/abrupt) was 0.6 (95% CI 0.3, 1.2)3.

2.1.2 There is moderate evidence from a large RCT ([++])1 of a benefit from NRT versus placebo at 6 months; this was more marked in the 4 mg gum versus 2 mg dose rates with ORs of 6.0 (95%CI 2.9, 12.3) and 1.8 (95% CI 1.1, 2.9) respectively. Overall OR 2.86 (95% CI 1.93, 4.24).

The evidence from 2 much smaller studies, a quasi-RCT (+)4 and an uncontrolled before-and-after study (–)5, is inconsistent. In the quasi–RCT mean quit rates for standard treatment versus behavioural counselling with NRT respectively at 6months were 21% versus 27% (NS) and at 12 months 26% versus 27% (NS)4. In the UCBA study5 39% reported abstinence at 6 months and 68% reported a 50% or above reduction in cigarette consumption at the end of 8 weeks using a combination of gum and behavioural therapy. The difference in abstinence between participants who wanted to reduce to quit versus those who were refractory smokers was not significant (48% versus 32%, p=0.8)5.

Applicability statement The evidence from the RCTs1–3 is partially applicable to people in the UK because, although there were no UK-based trials, the studies were community-based and are feasible within a UK setting. The Quasi-RCT relates specifically to recovering alcoholics4. The UBA was an intensive intervention which is unlikely to be feasible within the UK5.

1 Shiffman et al. 2009

2 Etter et al. 2009

3 Hughes et al. 2010

4 Martin et al. 1997

5 Jiménez-Ruiz et al. 2009

Evidence Statement 2.3.1 How effective are 'nicotine-containing products' in helping people cut down smoking before quitting?

For the purposes of this review 'nicotine containing products' were defined as 'electronic nicotine delivery systems' (sometimes known as 'electronic cigarettes' or 'e-cigarettes') and topical gels.

No studies were found that looked at the effectiveness of nicotine delivery systems (electronic cigarettes) for helping people to cut down before quitting.

Evidence Statement 2.4 (including statements 2.4.1–2.4.2) How effective are behavioural support, counselling, advice or self-help (with or without pharmacotherapy) in helping people cut down smoking before quitting?

2.4 Nine studies incorporated behavioural support, including 3 RCTs (1 [++]1, 1 [+]2,and 1 [−]3), 4 quasi-RCTs (all [+])4–7, 1 trial with partial randomisation (−)8 and 2 uncontrolled before-and-after studies (both [–])9,10.

Studies used behavioural intervention components in a variety of ways:

  • Cognitive behavioural support (both [+])4,7

  • Advice giving (+)2

  • Investigating the feasibility of contingency management(providing tangible reinforcers contingent on abstinence or reduction of substance use to a target level". The tangible reinforcers in this study were gift certificates) (–)8

  • Investigating the feasibility of computerised scheduled reduction (−)10.

In the other studies, all participants received a behavioural component (2 [+], 1 [++]1, 2 [–]3,5,6,9) and it is therefore not possible to infer the effectiveness of that component.

2.4.1 There is moderate evidence for the effectiveness of cognitive behavioural therapy versus standard therapy from 2 quasi-RCTs (both [+])4,7 both in reducing the number of cigarettes per day prior to quitting, and in quitting itself. At 12 months, 41% of the Cognitive Behavioural Therapy (CBT) group and 6% of the control group were abstinent, p<0.01. Figures for 6 months were 53% and 6%, p<0.014. At 12 months 19.8% (95% CI 13.0, 28.3) of the contactable CBT group were abstinent compared to 5.8 % (95% CI 2.1, 12.1, p<0.0001)7. At the same time point 11.5% (95% CI 6.4, 18.5, p<0.0001) had reduced their cigarettes per day (CPD) by 25% or more compared to 0% in the control group7.

2.4.2 There is moderate evidence from 2 RCTs (1 [++]1 and 1 [−])3 of a trend towards higher abstinence rates for abrupt cessation compared to gradual reduction when counselling is offered to both groups (in 1 study with nicotine1) but the findings are not significant. The OR for CO-verified abstinence at 6 months for gradual versus abrupt cessation, was 0.6 (95% CI 0.3, 1.2)1. At 12 months follow-up there was a non-significant difference in self-reported abstinence between sudden and gradual withdrawal groups: 51.85% versus 38.71%3.

2.4.3 There is weak evidence from one quasi-randomised trial5 (+) suggesting that cognitive behavioural therapy combined with advice to schedule and lengthen the time between cigarettes may enhance outcomes. Cotinine verified abstinence rates at 12 months were 44% (scheduled reduced), 18% (non-scheduled reduced), 32% (scheduled non-reduced) and 13% (non-scheduled non-reduced); p<0.05.

Applicability statement for evidence statements 2.4.1–2.4.7

This evidence is partially applicable to people in the UK. The use of rewards for response8 is unlikely in this setting. However one study was based in the UK7 and one was a web-based intervention2. All the other studies were community- or high school-based and feasible within a UK setting.

1 Hughes et al. 2010

2 Etter 2011

3 Gunther et al. 1992

4 Cinciripini et al. 1994

5 Cinciripini et al. 1995

6 Martin et al. 1997

7 Marks 2002

8 O'Leary Tevyaw 2007

9 Jiménez-Ruiz 2009

10 Riley 2002

Evidence Statement 2.5 (including statements 2.5.1–2.5.2) Is there an optimal period for helping people cut down smoking with the aim of quitting?

2.5 Eleven studies reported reduction periods, including 5 RCTs (2 [++]1,2 and 3[+]3–5), 3 quasi-RCTs (all [+])6–8, 2 uncontrolled before-and-after studies (both [–])9,10 and 1 secondary analysis of RCT data (−)11.

Among the included studies, the reduction period varied from 7–10 days8 through to 16 weeks9. Five studies employed reduction periods of between 2 and 5 weeks2,3,4,6,7. One10 utilised a 7-week schedule and 21,5 an 8-week schedule.

One study5 found no difference between 2 different reduction periods, although the interventions also differed. CO-verified quit rates at 12 months for the 3 groups (standard treatment with counselling over 4 weeks, counselling plus exercise and counselling plus NRT over 8 weeks) were 26%, 27% and 27% respectively.

None of the other included studies compared the effectiveness of different periods of cutting down prior to quitting. There was considerable variation in design between the studies and it is not possible to identify any relationship or trend between the length of the reduction period and the outcomes that is not subject to potential confounding by other aspects of the study designs.

However, 1 study11 carried out a secondary analysis to examine whether delaying a quit attempt was associated with less success. This analysis was considered to be at high risk of bias.

2.5.1 There is weak evidence from a quasi-RCT5 and a secondary analysis11 to indicate that there is no relationship between time to planned or actual quit date and long-term abstinence rate among those cutting down prior to quitting.

2.5.2 There is no evidence concerning the optimum cutting-down period from 9 studies1–4,6–10. Reduction periods varied from 7 days to 16 weeks. None of the studies explored the effect of the reduction time on outcomes and, given the huge heterogeneity between studies, no relationship between reduction time and outcomes can be inferred.

Applicability statement for evidence statements 2.5.1 and 2.5.2

This evidence is partially applicable to people in the UK who smoke, one study was a large community based study2 that may be feasible in the UK, although a secondary analysis is a methodologically weak study. One study looked specifically at recovering alcoholics5.

1 Shiffman 2009

2 Hughes 2010

3 Etter 2009

4 Etter 2011

5 Martin 1997

6 Cinciripini 1994

7 Cinciripini 1995

8 Marks 2002

9 Jiménez-Ruiz 2009

10 Riley 2002

Evidence Statement 2.6 (including evidence statements 2.6.1–2.6.2) Is it more or less effective to draw up a schedule to help someone cut down smoking with the aim of quitting?

2.6 One (+) quasi-RCT1 compared scheduled versus non-scheduled reduction. One (++) RCT2 and 1 (+) quasi-RCT3 compared different types of schedule.

2.6.1 There is weak evidence from 1 quasi-RCT1for scheduled versus non-scheduled reduction that cognitive behavioural therapy combined with advice to schedule and lengthen the time between cigarettes enhanced outcomes. Cotinine-verified abstinence rates at 12 months: 44% (scheduled reduced), 18% (non-scheduled reduced), 32% (scheduled non-reduced) and 22% (non-scheduled non-reduced); p<0.05.

2.6.2 There is weak evidence from 1 large RCT2 and 1 quasi-RCT3 that the type of smoking reduction schedule used does not make a difference. Reduction and abstinence rates did not appear to differ across the initially chosen methods (formal schedule, giving up 'easiest' cigarettes first, giving up 'hardest' cigarettes first) so the results were pooled across all the methods2. There was no difference between different intervention and scheduled reduction methods. CO-verified quit rates at 12 months for the 3 groups (standard treatment with counselling over 4 weeks, counselling plus exercise and counselling plus NRT over 8 weeks) were 26%, 27% and 27% respectively3.

Applicability statement for evidence statements 2.6.1 and 2.6.2

This evidence is partially applicable to people in the UK since the studies are community-based and feasible in UK settings. One study however, was in a specific population (recovering alcoholics)3.

1 Cinciripini 1995

2 Hughes 2010

3 Martin 1997

Evidence statements 3.1.1–3.1.3, 3.1.5, 3.1.6 How effective are pharmacotherapies in helping people cut down or abstain from smoking temporarily or indefinitely without the aim of quitting?

3.1.1 There is strong to moderate evidence from 9 studies: 2 RCTs1,2 (1 [++] and 1 [+]); 5 quasi-RCTs3–7 (3 [+] and 2 [−]) and 2 UBAs8,9 (both [−]) that NRT (gum or inhaler) versus placebo is effective in reducing cigarette consumption across multiple outcome measures and in eventual abstinence in smokers not looking to quit.

3.1.2 There is strong to moderate evidence from a meta-analysis of 3 RCTs1,2,10 (2 [++] and [+]) and 1 (+) quasi-RCT4 looking at 50% or more point prevalence reduction in CPD compared to baseline, that NRT, with or without a brief motivational interviewing (MI) component, is more effective than placebo with a relative risk (RR)=1.46 (95% CI 1.20, 1.78), with a number needed to treat (NNT) of 13 (95% CI 10, 20). A sensitivity analysis (excluding10 which added a brief MI component to NRT) resulted in RR=1.35 (95% CI: 1.10, 1.65) and an NNT of 17 (95% CI 10, 50). Smoking reduction was verified by CO except in2.

3.1.3 There is moderate evidence from a meta-analysis of 1 (++) RCT1 and 2 quasi-RCTs (both [+])3,7 that NRT is more effective than placebo in percentage reduction in cigarettes per day from baseline with a risk difference (RD) of −13.85 (95% CI: −25.5, −2.45).

3.1.5 There is strong evidence from a meta-analysis of 9 studies: 3 RCTs (2 [++]1,10 and 1 [+]2) and 6 quasi RCTs3,5,6,7,11,12 (all [+]) investigating cessation in populations not looking to quit that NRT with or without associated behavioural interventions has a statistically significant effect: RR=1.96 (95% CI 1.36, 2.80) with an NNT of 20 (95% CI 13, 34). A sensitivity analysis excluding studies with a behavioural component10,11,12 found a similar result for NRT alone: RR=1.93 (95%CI 1.26, 2.96) and an NNT of 20 (95% CI 13, 34).

3.1.6 There is moderate evidence from 1 (++) RCT13 of patients undergoing elective surgery that nicotine patch versus placebo is effective in reducing post-operative smoking consumption, a statistically significant self-reported reduction was observed 30 days post-operation but this was not maintained at 6 months.

Applicability statement for evidence statements 3.1.1–3.1.6

The majority of the evidence is applicable to the UK as the studies are community based and feasible in UK settings, although one study3 involved participants making several clinic visits, while another14 was in a laboratory setting. One study was conducted within a specific population (patients undergoing elective surgery)13.

1 Bolliger 2000

2 Etter 2007

3 Batra 2005

4 Hatsukami 2005

5 Kralikova 2009

6 Rennard 2006

7 Wennike 2003

8 Jiménez-Ruiz 2002

9 Rennard 1990

10 Chan

11Carpenter 2004

12Joseph 2008

13 Warner 2005

14Foulds 1992

Evidence statement 3.3.1 How effective are 'nicotine-containing products' in helping people cut down or abstain from smoking, temporarily or indefinitely without the aim of quitting?

Very weak evidence from 1 (−) UBA1 suggests that e-cigarette availability can help smokers reduce. This evidence may be applicable to the UK as it is community based and feasible in a UK setting.

1 Polosa 2011

Evidence statements 3.4.1–3.4.8 How effective are behavioural support, counselling, advice or self-help (with or without pharmacotherapy) in helping people to cut down or abstain from smoking, temporarily or indefinitely, without the aim of quitting?

3.4.1 There is consistent evidence from 7 studies: 2 RCTs1,2 (both [+]), 4 quasi-RCTs3,4,5,6 (all [+]) and 1 (−) CBA7 that motivational interviewing –compared with other behavioural methods or with no support and whether provided in single or multiple sessions – is not effective in helping people to reduce smoking levels. This evidence applies to healthy adolescents and adults, with no statistically significant differences between groups reported across any of the studies reviewed. Weak evidence also exists for the lack of effectiveness of motivational interviewing for adolescent drug users2,7 and military veterans with psychiatric problems6, with these studies again finding no significant differences between groups for the outcomes reported.

3.4.2 There is strong evidence from a meta-analysis of 2 RCTs1,2 (both [+]) and 3 quasi-RCTs3,4,5 (all [+]) that motivational interviewing – compared with other behavioural methods or with no support and provided in single or multiple sessions – is not effective for smoking cessation in populations unable or unwilling to stop smoking: RR 1.34 (95% CI 0.75, 2.39; p=0.32). This is at variance with findings of a Cochrane systematic review of smoking cessation (Lai 2010). One (++) RCT6 and 1 (+) quasi-RCT7 suggest that the addition of NRT to a motivational component may improve the likelihood of abstinence: RR 3.09 (95% CI 1.06, 9.01; p=0.04).

3.4.3 There is moderate evidence from a large well-conducted (++) RCT6 that NRT combined with a motivational component is effective, with a significant CO-validated 50% or more 7-day point prevalence reduction rate.

3.4.4 There is strong to moderate evidence from 4 studies:1(+) RCT8, 1 (+) quasi-RCT9, 1 (+) non-RCT10 and 1 (−) CBA11 designed to reduce the impact of environmental tobacco smoke on children – of no effect for a variety of behavioural methods versus standard care in reducing parental smoking. This evidence applies to parents of children with asthma9,10 as well as to parents of healthy children8,11.

3.4.5 There is moderate evidence from 2 RCTs12,13 (both [+]) and 1 (−) UBA14 that counselling combined with nicotine replacement therapy is not effective in helping adolescents12 or adults13,14 to reduce their cigarette consumption or to ultimately quit. There were no differences at follow-up between intervention and control groups for any smoking-related outcomes.

3.4.6 There is moderate evidence from 1 (++) RCT15 that telephone counselling is an ineffective approach to reducing cigarette consumption. At the 12 month follow-up there were no significant differences between intervention and control groups in terms of numbers reducing their daily cigarette consumption by 50% or more or in carbon monoxide levels.

3.4.7 There is moderate evidence from 1 (+) quasi-RCT16 that computer-aided and manual-aided approaches to assist with reduction had similar effect sizes. Twelve months after the start of the study there were no differences between groups in smoking reduction, and although more participants in the computer-aided group had made a quit attempt than in the manual-aided group, this difference was not statistically significant.

3.4.8 There is moderate evidence from 1 (+) systematic review of pre-operative smoking interventions17 that counselling combined with NRT increases smoking cessation at the time of surgery for both brief and intensive interventions. However, only intensive interventions were effective at 12 month follow-up: RR 2.96 (95% CI 1.57, 5.55) for 2 trials.

Applicability statement for evidence statements 3.4.1–3.4.8

The majority of evidence is applicable to the UK as the studies are feasible in UK settings. However 3 studies7,12,18 are noted to have issues regarding applicability. Studies of specific populations included adolescents3,4,12,19; adolescent drug users2,7; mental health18.20,21; patients undergoing elective surgery17,22,23; and parents8,9,10,11.

1 Horn 2007

2 McCambridge 2005

3 Kelly 2006

4 Audrain-McGovern 2011

5 Davis 2011

6 Gulliver 2008

7 Gray 2005

6 Chan 2011

7 Carpenter 2004

8 Hovell 2000

9 Irvine 1999

10 Wakefield 2002

11 Fossum 2004

12 Hanson 2008

13 Joseph 2008

14 Hurt 2000

15 Glasgow 2009

16 Riley 2002

17 Thomsen 2010

18 Tidey 2002

19 Horn 2007

20 Griffiths 2010

21Schleicher 2010

22 Munday 1993

23 Walker 2009

Evidence statements 3.6.1–3.6.2 Is it more or less effective to draw up a schedule to help people cut down or abstain from smoking, temporarily or indefinitely, without the aim of quitting?

3.6.1 Weak evidence from 2 quasi-RCTs (1 [+]1 and 1 [−]2) and 2 UBAs (both [−])3,4 suggests using a schedule may assist in reducing smoking. Schedules included week-on-week reduction3,4, increased inter-cigarette interval or selective elimination1,2.

3.6.2 There is limited evidence from 2 quasi-RCTs (1 [+]1 and 1 [−]2) of no difference in effect between different types of schedule (increasing inter-cigarette intervals or selective elimination).

Applicability statement for evidence statements 3.6.1 and 3.6.2

The evidence is partially applicable to people in the UK since all 4 studies were community-based (in the USA) and are feasible in UK settings.

1 Riley 2002

2 Riggs 2001

3 Hatsukami 2005

4 Hurt 2000

Evidence statements 3.8.1–3.8.3 Are there any unintended consequences from adopting a tobacco harm-reduction approach; for example, does it deter people from trying to cut down or abstain from smoking, temporarily or indefinitely?

3.8.1 There is strong evidence from 8 studies: 3 RCTs1,2,3 (1[++]1 and 2 [+]2,3), 3 quasi-RCTs4,5,6 (all [+]) and 2 UBA(1 [+]7 and 1 [−]8) reporting usage of NRT for periods between 6 months and 5 years – to suggest that NRT is generally well-tolerated long term with severe side effects being relatively rare.

3.8.2 There is moderate evidence from 2 quasi-RCTs6,9 (both [+]) that harm-reduction interventions do not deter smokers from wishing to quit.

3.8.3 There is weak evidence from a single (−) UBA10 that frequent adverse events are reported by e-cigarette users. This finding supports the conclusions from review 1 that more evidence is required concerning the safety of e-cigarettes.

Applicability statement for evidence statements 3.8.1–3.8.3

Adverse event studies are likely to be applicable to the UK.

1 Bollinger 2000

2 Etter 2007

3 Joseph 2008

4 Batra 2005

5 Kralikova 2009

6 Wennike 2003

7 Rennard 2006

8 Jiménez-Ruiz 2002

9 Carpenter 2004

10 Polosa 2011

Evidence statement 4.1.4 Background environment factors described by smokers: social pressure to change smoking behaviour as a facilitator

Social pressure from friends, family or society in general to reduce, quit or implement smokefree homes and cars was described as a facilitator in 8 studies(1 [++]1, 6 [+]2–7,and 1 [−]8). Smokers in 1 study were professionally supported to address their smoking behaviour7.

1 Bottorff 2009

2 Bolliger 2000

3 Richter 2002

4 Stewart 2011

5 Abdullah 2011

6 Herbert 2011

7 Phillips 2007

8 Green 2005

Evidence statement 4.1.5 Background environment factors described by smokers: social support from friends, family and professionals as a facilitator

Social support from friends, family or professionals was perceived to be helpful in reducing smoking consumption in 3 (+) studies1–3. One study1 involved surgery outpatients in receipt of a smoking telephone counselling intervention to reduce smoking consumption. Another study2 involved low income women describing attitudes to smoking reduction or quitting and the third included adolescents describing ways in which they control smoking levels3.

1 Estabrooks 2010

2 Stewart 2011

3 Johnson 2004

Evidence statement 4.1.7 Background environment factors described by smokers: smoking restrictions promote smoking reduction

Eight studies (1 [++]1, 4 [+]2–5 and 3 [−]6–8) included participants reporting that smoking restrictions helped them to reduce their smoking whether in: the home1,2,6 at work7 or in hospital8.

1 Jones 2003

2 Abdullah 2011

3 Herbert 2011

4 Phillips 2007

5 Robinson 2010

6 Blackburn 2003

7 Amos 1995

8 Keizer 2009

Applicability statement for evidence statements 4.1.1–4.1.7

Just 71–7 of the 21 studies on background environment factors described by smokers were based in the UK and 28–9 from countries judged to have similar applicability to the UK.

1 Amos 1995

2 Beard 2011a

3 Blackburn 2003

4 Haddock 1997

5 Jones 2011

6 Phillips 2007

7 Robinson 2010

8 Hamilton 2000

9 Thomsen 2009

Evidence statement 4.1.10 Smokers' attitudes, beliefs and experiences regarding THR efforts: smokers' perceived low ability in achieving smoking goals

A common theme across 3 studies (2 [+]1,2, 1 ungraded3) was that participants' lack of confidence in their ability to achieve their smoking goals was a barrier to changing smoking behaviour. These studies were conducted in potentially more vulnerable groups: pre-surgical patients3; low income women1 and adolescents2. One study included smokers that were receiving professional support to address their smoking behaviour3.

1 Stewart 2011

2 Johnson 2004

3 Haddock 1997

Evidence statement 4.1.11 Smokers' attitudes, beliefs and experiences regarding THR efforts: perceived high nicotine dependence/smoking addiction

The addictive effect of smoking and the difficulty of resisting subsequent cravings were described as barriers to reducing smoking or implementing smokefree homes in 3 studies (1 [++]1, 1 [+]2 and 1 [−]3). However, in a further (+) study4, perceived dependence on smoking was not associated with quitting success among smokers who first cut down without professional support. The studies were conducted in general adult smokers4, psychiatric inpatients3 and parents and/or new fathers with children living at home1,2. One study included smokers that were professionally supported to address their smoking behaviour2.

1 Bottorff 2009

2 Herbert 2011

3 Keizer 2009

4 Cheong 2007

Evidence statement 4.1.15 Smokers' attitudes, beliefs and experiences regarding THR efforts: smokers' own structuring and scheduling of smoking

Eight studies (1 [++]1 and 7 [+])2–8)identified that smokers use structuring or scheduling smoking techniques to limit or reduce their cigarette consumption or temporarily abstain was a facilitator to change. These included: half-butting or smoking part of the cigarette1–4; inhaling less or not at all2,4; carrying only a set number of cigarettes5; borrowing cigarettes instead of buying3; cutting out unnecessary cigarettes for example, not chain smoking2,3; restricting the number of cigarettes smoked, where or when smoked2,3,4,6 or delaying time between cigarettes1,2,3,7,8. Three studies included smokers that were using NRT2,4 or receiving behavioural interventions to achieve smoking goals5.

1 Bottorff 2009

2 Beard 2011a

3 Johnson 2004

4 Okuyemi 2001

5 Estabrooks 2010

6 Nguyen 2009

7 Poland 2009

8 Robinson 2010

Evidence statement 4.1.17 Smokers' attitudes, beliefs and experiences regarding THR efforts: smokers' wish to protect children from smoke

Seven studies (2 [++]1,2 and 5 [+]3–7) reported wishing to protect the health of their children as a facilitator to reducing their smoking3 or in implementing smokefree homes1,2,4–6. Smokers in 1 study were receiving professional support to address their smoking behaviour4.

1 Bottorff 2009

2Jones 2011

3 Nichter 2008

4 Abdullah 2011

5 Herbert 2011

6 Phillips 2007

7 Poland 2009

Evidence statement 4.1.18 Smokers' attitudes, beliefs and experiences regarding THR efforts: smokers' worries of harm to own health from smoking

Concern about the effect of tobacco on smokers' own health was a commonly reported facilitator across 13 studies (1 [++]1, 10 [+]2–11, 1 [−]12 and 1 ungraded13) looking at reducing smoking or implementing smokefree homes. Smokers described both worries of harm to their own health2–7,13 and perceived benefits to health from reduction of smoking1,8–10,12. However 1 study found that worries about damage to health and quality of life from smoking or perceived benefits to health from quitting, were not associated with quitting success among smokers who first cut down11. Smokers' in 2 studies were receiving professional support to address their smoking behaviour3,13.

1 Bottorff 2009

2 Bolliger 2000

3 Estabrooks 2010

4 Abdullah 2011

5 Poland 2009

6 Stewart 2011

7 Hamilton 2000

8 Beard 2011a

9 Joseph 2005

10 Shiffman 2007

11Cheong 2007

12 Thomsen 2009

13Haddock 1997

Applicability statement for evidence statements 4.1.8–4.1.18

Of the 22 studies reporting smokers views regarding tobacco harm reduction, just 6 studies were solely conducted in the UK (1 [++]1, 4 [+]2–5,and 1 [−]6), 1 (+) study in multiple countries including the UK7 and 1 (+) study in a country deemed to have high applicability to the UK8.

1 Jones 2011

2 Beard 2011a

3 Haddock 1997

4 Robinson 2010

5 Phillips 2007

6 Thomsen 2009

7 Cheong 2007

8 Hamilton 2000

Evidence statement 4.1.37 Smokers' attitudes, beliefs and experiences regarding e-cigarette use to assist THR: belief that e-cigarettes do not help with smoking craving

There was limited evidence from 1 cross-sectional survey (+)1 that a small proportion of e-cigarette users (10%) believed that the product did not help with cravings in smokers aiming to cease or reduce smoking.

1 Etter 2011

Evidence statement 4.1.42 Smokers' attitudes, beliefs and experiences regarding e-cigarette use to assist THR: e-cigarettes are perceived as less harmful than smoking

There was evidence from 2 cross-sectional surveys that a facilitator to change was the perception that e-cigarettes are less harmful to others or their own health than smoking by the majority of participants (1 [+]1 and 1 [−]2)and perceived to help with withdrawal and craving symptoms of nicotine2.

1 Etter 2011

2 Foulds 2011

Applicability statement for evidence statements 4.1.37–4.1.43

The evidence has limited applicability to the UK. One (+) study1included UK participants, although the majority were from USA and other countries. One (−) study2 was conducted in a potentially biased sample of USA e-cigarette users attending an e-cigarette enthusiast meeting.

1 Etter 2011

2 Foulds 2011

Evidence statement 4.2.6

Five studies (2 [+]1,2, 3 [−]3–5) examined barriers and facilitators encountered by mental health populations, from the perspective of patients and health workers. Common themes were boredom and a strong dependence on smoking1,3,4 Many patients believed they were not offered adequate advice or assistance to address their smoking1,4.This is supported in two studies by the relatively low proportion of mental health workers who considered smoking advice was an important part of their role2,5.

Applicability statement for evidence statements 4.2.1–4.2.6 Three studies were based in the UK1,2,6 and two studies were identified from Australia that is likely to have UK applicable evidence regarding adolescents5 and psychiatric services7.

1 Ratschen 2010

2 Ratschen 2009

3 Keizer 2009

4 Green 2005

5 Ashton 2010

6 Jones 2011

7 Hamilton 2000

Evidence statement 5.1 Long-term NRT use

There is moderate evidence of long-term (12 months) NRT use in a small number of people who had quit smoking. The evidence is provided by 3 RCTs1–3 (all [++]), 2 prospective cohort studies4,5 (both [+]) and 1 (−) UBA6. This extended use is beyond the length of time that is recommended, treatment is usually between 8 and 12 weeks before the dose is reduced and eventually stopped. From the studies that provided 12-month follow-up data, 7% (range 3–11%) of individuals who had quit smoking were still using NRT. This evidence is for nasal spray1,3,5 nicotine gum2,6 and a range of NRT products4.

1 Blondal 1999

2 Bjornson-Benson 1993; Murray 1996; Nides 1995

3 Sutherland 1992

4 Hajek 2007

5 Schneider 2003

6 Hatsukami 1993

Evidence statement 5.2 Long-term NRT use

There is moderate evidence that most long-term (12 months or over) use of nicotine gum or spray is within recommended dosage limits. The evidence is provided by 2 RCTs1,2 (both [++]), 1 (+) prospective cohort study3 and 2 cross-sectional surveys4,5 (both [–]). For this dosage evidence participants in 3 studies1,2,3 had quit smoking but the smoking status was not reported for participants in the other 2 studies4,5.

1 Blondal 1999

2 Bjornson-Benson 1993; Murray 1996

3 Schneider 2003

4 Hughes 2004

5 Johnson 1991

Evidence statement 5.3 Long-term NRT use

There is moderate evidence from 1 (++) RCT1and 1 (+) prospective cohort study2 that nicotine dependence at baseline is a predictor of long-term NRT use at 12 months1,2. The data was from participants who had all quit smoking.

1 Bjornson-Benson 1993

2 Hajek 2007

Applicability statement for evidence statements 5.1–5.3

This evidence is directly applicable to people in the UK who attempt to quit smoking abruptly. Of the studies that reported NRT use at 12 months in former smokers, 2 studies were conducted in the UK (1 [++]1 and 1 [+]2) and 3 were conducted in community settings (2 [++]3,4 and 1 [−]5).

1 Sutherland 1992

2 Hajek 2007

3 Blondal 1999

4 Bjornson-Benson 1993; Murray 1996; Nides 1995

5 Hatsukami 1993

Evidence statement 5.4 Long term e-cigarette use

There is no evidence of e-cigarette use for periods of 12 months or longer in individuals who quit smoking abruptly and insufficient evidence of the pattern of use.

Evidence statement 5.5 Long term e-cigarette use

There is weak evidence from 3 cross-sectional surveys (1 [+]1 and 2 [−]2,3), possibly of e-cigarette enthusiasts, that e-cigarettes are used for 12 months or longer. Only 1 study3 reports that some individuals have completely replaced cigarettes with e-cigarettes. There was no evidence related to the dosage used by long term e-cigarette users.

1 Etter 2011

2 Foulds 2011

3 Heavner 2010

Evidence statement 5.6 Long term e-cigarette use

No evidence was identified on predictors or purchase patterns of e-cigarette use.

Applicability statement for evidence statements 5.4–5.6

The evidence is only partially applicable to people in the UK who quit smoking abruptly. This is because e-cigarettes are not licensed for smoking cessation. There is evidence from 3 cross-sectional surveys (1 [+]1, 2 [−]2,3) in which participants were possibly e-cigarette enthusiasts3. However, the evidence does indicate that e-cigarettes are used in the UK1,2 though it does not indicate if any of the e-cigarette users quit smoking abruptly.

1 Etter 2011

2 Heavner 2010

3 Foulds 2011

Economic modelling

Overall, tobacco harm reduction approaches were found to be cost effective.

Five comorbidities (lung cancer, chronic obstructive pulmonary disease, stroke, myocardial infarction and coronary heart disease) were included in the model, as well as all-cause mortality.

Seven key 'quit' or 'reduce' scenarios, using various delivery routes, were assessed. A total of 21 scenarios (that is, individual or multi-component interventions) were modelled in the main analysis. The comparator in all cases was 'no intervention'.

Of the scenarios which sought to help someone quit or reduce their consumption, 3 were cost saving and 12 were highly cost effective. The latter ranged from an estimate of £437 per quality-adjusted life year (QALY) to £8464 per QALY. Of the scenarios based around temporary abstinence, 5 were highly cost effective and 1 showed no benefit. The former ranged from an estimated £765 per QALY to £8464 per QALY.

A sensitivity analysis of abrupt quitting supported by long-term nicotine-containing products estimated that the use of nicotine-containing products was cost effective for nearly all the scenarios. (Effectiveness of quit rate varied from 0–20%; duration of use of nicotine-containing products varied from 6 months to 10 years.)

The costs only potentially outweighed the benefits when nicotine-containing products were provided for more than 5 years, and the quit rate was less than 4%, or the products were provided for more than 10 years and the quit rate was less than 6%.

Supplementary analysis

A supplementary analysis assumed there were no benefits from smoking reduction (in terms of QALYs and comorbidities), other than an increased likelihood of quitting at 6 months. It showed that, as the effectiveness of an intervention diminishes, so the time during which it is considered cost effective to provide NCPs reduces. For example, the costs potentially outweigh the benefits when the reduction rate is 6% or less, and someone uses a nicotine-containing product for 12 months or longer. If a reduction of 20% or more is achieved, the product can be used for up to 2 years before it exceeds the £20,000 QALY threshold for cost effectiveness.

It was anticipated that there may be some trade-off between the number of people quitting and the number who reduce the amount they smoke, according to the approach used. For example, by offering services to help people to reduce their smoking intake, it is plausible that some people who may otherwise have chosen (or attempted) to quit decide not to.

An analysis of the benefits associated with either quitting smoking or reducing smoking for a person aged 50 was undertaken. The model estimated that an intervention that achieves 1 additional 'reducer' will provide an additional 0.45 QALYs. It will also save the NHS approximately £767 over the person's lifetime. An intervention that achieves 1 quitter, however, will gain 0.84 QALYs and will save the NHS £1412 over the same period.

In other words, the benefits of reducing are approximately half those of quitting. So, for each 'quitter' drawn into reducing instead, any intervention would need to get at least 2 more people to reduce their smoking to offset that loss. The supplementary analysis showed that, for each potential quitter lost, 6 more 'reducers' would be needed to offset the lost benefits.

Clearly, it would be better to gain 1 quitter rather than 1 reducer. However, by offering services to help people to reduce the amount they smoke, more people may present for treatment, leading to additional benefits to society.

Fieldwork findings

Fieldwork aimed to test the relevance, usefulness and feasibility of putting the recommendations into practice. The PDG considered the findings when developing the final recommendations. For details, go to Fieldwork and Tobacco: harm-reduction approaches to smoking – final fieldwork report.

Fieldwork participants who work with smokers were fairly positive about the recommendations and their potential to help reduce the harm from smoking, so long as the harm-reduction approaches were a step towards stopping smoking.

Many participants stated that provision of support for tobacco harm-reduction would involve a substantive addition to current practice. However, some services were already using a 'cut down to quit approach'.

The majority of participants did not welcome the idea of encouraging people to reduce their smoking without ever planning to stop.

Many participants were positive about those parts of the recommendations that emphasised abrupt quitting as the best way to improve the health of people who smoke. There were, nonetheless, widespread concerns about the potential negative impact that the recommendations as a whole could have.

Some thought that presenting smokers with an option to reduce their smoking (indefinitely as they understood it) rather than stopping smoking, presented an 'easy way out'.

Most commissioners thought that the evidence for the health benefits and cost effectiveness of a harm reduction approach were insufficient to justify the significant changes and costs required to implement the recommendations. Concern about costs also focused on long-term funding of NRT and funding of services within 'payment by results' contract models (where payment is typically attached to someone stopping smoking).

  • National Institute for Health and Care Excellence (NICE)