Relapse prevention interventions for smoking cessation

  • Review
  • Intervention

Authors


Abstract

Background

A number of treatments can help smokers make a successful quit attempt, but many initially successful quitters relapse over time. Several interventions have been proposed to help prevent relapse.

Objectives

To assess whether specific interventions for relapse prevention reduce the proportion of recent quitters who return to smoking.

Search methods

We searched the Cochrane Tobacco Addiction Group trials register in May 2013 for studies mentioning relapse prevention or maintenance in title, abstracts or keywords.

Selection criteria

Randomized or quasi-randomized controlled trials of relapse prevention interventions with a minimum follow-up of six months. We included smokers who quit on their own, were undergoing enforced abstinence, or were participating in treatment programmes. We included trials that compared relapse prevention interventions with a no intervention control, or that compared a cessation programme with additional relapse prevention components with a cessation programme alone.

Data collection and analysis

Studies were screened and data extracted by one review author, and checked by a second. Disagreements were resolved by discussion or by referral to a third review author.

Main results

Sixty-three studies met inclusion criteria but were heterogeneous in terms of populations and interventions. We considered 41 studies that randomly assigned abstainers separately from studies that randomly assigned participants before their quit date.

Upon looking at studies of behavioural interventions that randomly assigned abstainers, we detected no benefit of brief and 'skills-based' relapse prevention methods for women who had quit smoking because of pregnancy, or for smokers undergoing a period of enforced abstinence during hospitalisation or military training. We also failed to detect significant effects of behavioural interventions in trials in unselected groups of smokers who had quit on their own or through a formal programme. Amongst trials randomly assigning smokers before their quit date and evaluating the effects of additional relapse prevention components, we found no evidence of benefit of behavioural interventions or combined behavioural and pharmacotherapeutic interventions in any subgroup. Overall, providing training in skills thought to be needed for relapse avoidance did not reduce relapse, but most studies did not use experimental designs best suited to the task and had limited power to detect expected small differences between interventions. For pharmacological interventions, extended treatment with varenicline significantly reduced relapse in one trial (risk ratio (RR) 1.18, 95% confidence interval (CI) 1.03 to 1.36). Pooling of six studies of extended treatment with bupropion failed to detect a significant effect (RR 1.15, 95% CI 0.98 to 1.35). Two small trials of oral nicotine replacement treatment (NRT) failed to detect an effect, but treatment compliance was low, and in two other trials of oral NRT in which short-term abstainers were randomly assigned, a significant effect of intervention was noted.

Authors' conclusions

At the moment, there is insufficient evidence to support the use of any specific behavioural intervention to help smokers who have successfully quit for a short time to avoid relapse. The verdict is strongest for interventions focused on identifying and resolving tempting situations, as most studies were concerned with these. Little research is available regarding other behavioural approaches.

Extended treatment with varenicline may prevent relapse. Extended treatment with bupropion is unlikely to have a clinically important effect. Studies of extended treatment with nicotine replacement are needed.

Résumé scientifique

Interventions de prévention des rechutes pour l'arrêt du tabac

Contexte

Un certain nombre de traitements peuvent aider les fumeurs à réussir à arrêter de fumer, mais parmi eux, nombreux sont ceux qui rechutent avec le temps. Plusieurs interventions ont été proposées pour aider à prévenir les rechutes.

Objectifs

Déterminer si des interventions spécifiques pour la prévention des rechutes réduisent la proportion d'ex-fumeurs récents qui se remettent à fumer.

Stratégie de recherche documentaire

En mai 2013, nous avons recherché dans le registre du groupe Cochrane sur le tabagisme des études mentionnant la prévention des rechutes ou la maintenance dans les titres, résumés ou mots clés.

Critères de sélection

Des essais contrôlés randomisés ou quasi-randomisés portant sur des interventions de prévention des rechutes et ayant réalisé un suivi d'au moins six mois. Nous avons inclus les fumeurs ayant arrêté de fumer seuls, ou ceux à qui l'abstinence avait été imposée ou ceux qui participaient à des programmes de traitement. Nous avons inclus les essais ayant comparé des interventions de prévention des rechutes à un contrôle sans intervention, ou ayant comparé un programme de sevrage incluant des éléments de prévention des rechutes à un programme de sevrage simple.

Recueil et analyse des données

Les études ont été pré-sélectionnées et les données extraites par un auteur puis vérifiées par un second. Les désaccords ont été résolus par la discussion ou par recours à un troisième auteur.

Résultats principaux

Soixante-trois études répondaient aux critères d'inclusion, mais elles étaient hétérogènes en terme de populations et d'interventions. Nous avons retenu 41 études ayant randomisé des abstinents séparément des études ayant randomisé les participants avant leur date de sevrage.

En examinant des études sur des interventions comportementales ayant randomisé des personnes abstinentes, nous n'avons pas mis en évidence de bénéfice pour les méthodes de prévention des rechutes brèves et «Â axées sur les compétences » chez les femmes ayant arrêté de fumer durant leur grossesse ou pour les fumeurs contraints à l'abstinence au cours d'une hospitalisation ou lors d'une formation militaire. Nous n'avons également pas pu montrer d'effets significatifs des interventions comportementales dans des essais sur des groupes non sélectionnés de fumeurs ayant arrêté de fumer seuls ou à l'aide d'un programme formalisé. Nous n'avons également pas trouvé de bénéfice évident pour des interventions comportementales dans un quelconque sous-groupe parmi les essais ayant randomisé des fumeurs avant leur date d'arrêt et ayant évalué l'effet d'éléments supplémentaires de prévention des rechutes. Dans l'ensemble, la formation aux compétences jugées nécessaires pour éviter les rechutes ne les avait pas réduites, mais la plupart des études n'avaient pas utilisé les modèles expérimentaux les mieux adaptés à la tâche et n'avaient qu'un pouvoir limité pour mettre en évidence des petites différences entre les interventions. Pour ce qui concerne les interventions pharmacologiques, un traitement prolongé par varénicline avait significativement réduit les rechutes dans un essai (risque relatif 1,18 ; intervalle de confiance à 95 % 1,03 à 1,36). Le regroupement de six études sur le traitement prolongé par bupropion n'a pas permis de montrer d'effet significatif (risque relatif 1,15 ; intervalle de confiance à 95 % 0,98 à 1,35). Deux petits essais avec un traitement oral de substitution nicotinique n'ont pas montré d'effet, mais l'observance au traitement était faible et dans deux autres essais avec un traitement par substitut nicotinique oral ayant randomisé des personnes ayant récemment arrêté de fumer, l'intervention avait produit un effet significatif.

Conclusions des auteurs

À l'heure actuelle il n'y a pas suffisamment de preuves pour recommander l'utilisation d'une quelconque intervention comportementale pour aider les fumeurs ayant récemment arrêté de fumer à éviter une rechute. Le verdict est le plus fort pour les interventions axées sur l'identification et la résolution des situations propices aux tentations, la plupart des études ayant porté sur cela. Il existe peu de recherches disponibles sur d'autres approches comportementales.
Un traitement prolongé par varénicline pourrait prévenir les rechutes. Un traitement prolongé par bupropion n'a probablement pas d'effet cliniquement important. Des études sont nécessaires sur les traitements prolongés par substituts nicotiniques.

Plain language summary

Do any interventions help smokers who have successfully quit for a short time to avoid relapsing?

Some people start smoking again shortly after quitting and are said to have 'relapsed'. Interventions used to help people avoid relapse usually focus on teaching the skills to cope with temptations to smoke. This approach and others have not been shown to be helpful, either for people who quit on their own or with the help of treatment, or for those who quit because they were pregnant or in hospital. Many trials conducted so far have not been of a strong enough design to detect possible small effects. Among drug treatments, extended use of varenicline may help some smokers. Studies of extended use of nicotine replacement treatment are urgently needed.

Résumé simplifié

Certaines interventions aident-elles les fumeurs ayant récemment réussi à arrêter de fumer à éviter les rechutes ?

Certaines personnes recommencent à fumer peu de temps après avoir arrêté ; on parle alors de « rechute ». Les interventions destinées à aider les personnes à éviter la rechute sont centrées généralement sur l'enseignement de compétences permettant de faire face aux tentations de fumer. Ni cette approche ni d'autres ne se sont avérées utiles, que les personnes soient parvenues seules à arrêter de fumer, qu'elles aient bénéficié d'une aide thérapeutique au sevrage ou qu'elles aient arrêté de fumer parce qu'elles étaient enceintes ou hospitalisées. De nombreux essais réalisés jusqu'à présent n'ont pas été conçus de façon suffisamment solide pour détecter d'éventuels effets légers. En matière de traitements médicamenteux, l'utilisation prolongée de la varénicline pourrait aider certains fumeurs. Des études sur l'utilisation prolongée de traitements par substitution nicotinique sont nécessaires de façon urgente.

Notes de traduction

Traduit par: French Cochrane Centre 29th August, 2012
Traduction financée par: Ministère du Travail, de l'Emploi et de la Santé Français

Laički sažetak

Postoje li ikakve intervencije koje pomažu pušačima koji su uspješno prestali pušiti da ne počnu ponovo s pušenjem?

Neki ljudi počinju ponovno pušiti ubrzo nakon što prestanu s pušenjem, što se naziva "relaps". Intervencije koje se koriste kako bi pomogle ljudima da izbjegnu relapse obično su usmjerene na učenje vještina za nošenje s iskušenjima koja bih ih mogla navesti na ponovni početak pušenja. Nije se pokazalo da je taj pristup djelotvoran, bilo za osobe koje prestanu sami ili uz pomoć liječenja, ili za osobe koje su prestale pušiti zbog trudnoće ili liječenja u bolnici. Mnoge studije dosad provedene nisu bile dovoljno jake da bi se u njima mogli otkriti mogući mali učinci različitih pristupa tom problemu. Među lijekovima nekim pušačima može pomoći produljeno uzimanje vareniklina. Studije o produljenoj uporabi zamjenskih terapija nikotinom prijeko su potrebne.

Bilješke prijevoda

Hrvatski Cochrane
Prevela: Ivana Sruk
Ovaj sažetak preveden je u okviru volonterskog projekta prevođenja Cochrane sažetaka. Uključite se u projekt i pomozite nam u prevođenju brojnih preostalih Cochrane sažetaka koji su još uvijek dostupni samo na engleskom jeziku. Kontakt: cochrane_croatia@mefst.hr

Streszczenie prostym językiem

Czy istnieją interwencje, które pomagają zapobiec nawrotowi u palaczy, którzy zaprzestali palenia tytoniu na krótki okres czasu?

Niektóre osoby ponownie rozpoczynają palenie tytoniu niedługo po rzuceniu nałogu; nazywane jest to "nawrotem". Interwencje wspomagające zapobieganie nawrotom zazwyczaj polegają na nauce radzenia sobie z pokusą palenia tytoniu. Takie oraz inne podejścia nie okazały się skuteczne zarówno u palaczy, którzy rzucili palenie tytoniu samodzielnie lub z pomocą leczenia, jak i u tych, którzy rzucili palenie z powodu ciąży lub pobytu w szpitalu. Wiele przeprowadzonych dotychczas badań nie zostało zaprojektowanych wystarczająco dobrze, aby wykryć możliwie niewielkie efekty. Spośród interwencji farmakologicznych, przedłużone stosowanie warenikliny może być pomocne u niektórych palaczy. Pilnie potrzebne jest przeprowadzenie badań dotyczących przedłużonego stosowania nikotynowej terapii zastępczej.

Uwagi do tłumaczenia

Tłumaczenie: Paulina Kaźmierska Redakcja: Karolina Moćko

Summary of findings(Explanation)

Summary of findings for the main comparison. Behavioural interventions for assisted abstainers
  1. 1Control group cessation rate calculated as crude average of quitters in control groups across all studies that randomly assigned abstainers.
    2Majority of included studies judged to be at unclear or high risk of bias in two or more domains.
    3Moderate unexplained statistical heterogeneity (I2 = 56%).
    4Total number of events < 300.

Behavioural interventions for relapse prevention for people who have quit smoking using a cessation intervention
Patient or population: people who have quit smoking using a cessation intervention
Intervention: behavioural interventions for relapse prevention
OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments
Assumed riskCorresponding risk
Control Behavioural interventions for relapse prevention
Smoking cessation
Follow-up: 9 to 15 months
Study population (average)1 RR 1
(0.87 to 1.15)
1462
(5 studies)
⊕⊝⊝⊝
very low 2,3,4
 
300 per 1000 300 per 1000
(261 to 345)
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio.
GRADE Working Group grades of evidence:
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Summary of findings 2 Pharmacotherapy for assisted abstainers

Summary of findings 2. Pharmacotherapy for assisted abstainers
  1. 1Total number of events < 100.
    2 Control group cessation rate calculated as crude average of quitters in control groups across all studies that randomly assigned abstainers.
    3Total number of events < 300.

Pharmacotherapy for relapse prevention for people who have quit smoking using a cessation intervention
Patient or population: people who have quit smoking using a cessation intervention
Intervention: pharmacotherapy for relapse prevention
OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments
Assumed riskCorresponding risk
Control Pharmacotherapy for relapse prevention
NRT versus placebo. Smoking cessation
Follow-up: 12 to 15 months
Study population (average)2 RR 1.04
(0.77 to 1.4)
553
(2 studies)
⊕⊕⊝⊝
low 1
 
300 per 1000 312 per 1000
(231 to 420)
Bupropion versus placebo. Smoking cessation
Follow-up: 12 to 24 months
Study population (average)2 RR 1.15
(0.98 to 1.35)
1697
(6 studies)
⊕⊕⊕⊝
moderate 3
 
300 per 1000 345 per 1000
(294 to 405)
Combination NRT & bupropion versus placebo. Smoking cessation
Follow-up: 12 to 15 months
Study population (average)2 RR 1.18
(0.75 to 1.87)
243
(2 studies)
⊕⊕⊝⊝
low 1
 
300 per 1000 354 per 1000
(225 to 561)
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio.
GRADE Working Group grades of evidence:
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Background

A number of interventions can help people who smoke to quit. These include pharmacological treatments, such as nicotine replacement, some antidepressants and nicotine receptor partial agonists; and behavioural approaches, whether delivered individually or in groups (Lancaster 2005; Stead 2005; Hughes 2007; Stead 2012). These interventions increase long-term quit rates compared with control interventions, but there is a steady attrition in overall success rates due to a proportion of initially successful participants returning to smoking over time (relapsing).

Several strategies for relapse prevention have been examined in randomized controlled trials. The most widely studied has been the skills approach, whereby patients learn to identify high-risk situations for relapse and are provided with cognitive and behavioural strategies to cope with these situations (Marlatt 1985; Marlatt 2008). A smaller number of studies have tested alternative psychological treatments (usually combined with the skills approach). These include imaginary cue exposure, writing tasks, aversive smoking, role-play, social support, and exercise. A separate group of studies have tested the effects of preventing relapse by extending the duration of therapeutic contact. Finally, studies have examined pharmacological treatments for relapse prevention.

There is no clear definition of a relapse prevention intervention as distinct from an extended cessation treatment because, in principle, resumption of smoking at any time after the quit date can count as relapse. In general, relapse prevention is considered to apply to interventions that explicitly seek to reduce relapse rates after an acute treatment phase is successfully completed, or at some time after the quit date of a self-quit attempt. The duration of the acute treatment phase varies, leading to variability in the point at which measurement of a relapse prevention effect begins. This is unavoidable, and the approach adopted in this review is to consider as relapse prevention interventions that are designated by the authors as such, or interventions involving extended treatment after what would be the normal treatment duration.

Trials of interventions for relapse prevention may randomly assign people who have already quit, or they may randomly assign smokers before their quit attempt and provide a general smoking cessation intervention to all participants, in addition to an extra component provided for those randomly assigned to relapse prevention. The former design has a number of methodological strengths, which are discussed later in this review. We have included both types of study in the review.

The aim of reviewing evidence of efficacy of relapse prevention interventions was to provide information for care providers that may be relevant when they must decide how to allocate resources between motivating attempts to stop smoking, supporting smokers who need help during the initial stages of their quit attempt and providing further support to prevent relapse.

Objectives

To assess whether specific interventions for relapse prevention reduce the proportion of recent quitters who return to smoking.

Methods

Criteria for considering studies for this review

Types of studies

Randomized or quasi-randomized controlled trials with a minimum follow-up of six months from quit date.

Types of participants

We considered three types of participants: people who had quit smoking on their own; people who were undergoing enforced abstinence, whether or not they intended to quit permanently; and smokers participating in treatment programmes to assist initial cessation.

Types of interventions

We included interventions identified by study investigators as intended to prevent relapse, compared with no intervention or a shorter intervention or an intervention not oriented towards relapse prevention. We considered behavioural interventions delivered in any format, including group meetings, face-to-face sessions, written or other materials, proactive or reactive telephone support, and pharmacological interventions.

Types of outcome measures

The preferred outcome was prolonged or multiple point prevalence abstinence at follow-up of at least six months since randomization. We also included trials that reported only point prevalence abstinence (number of participants not smoking at the point when assessment is made-abstinent at that time but not necessarily continuously since treatment) at six months or longer. For studies that reported more than one definition of abstinence, we considered whether the choice of outcome would affect any pooled effect estimate. We excluded studies with less than six months follow-up.

Search methods for identification of studies

We searched the Cochrane Tobacco Addiction Group register of trials, which includes the results of comprehensive searches of electronic bibliographic databases and conference abstracts. We checked for relevance all reports of trials with 'relapse prevention' or 'maintenance' or 'relapse near prevent*' in title, abstract or keywords. See Appendix 1 for the full strategy. At the time of the search in May 2013, the Register included the results of searches of the Cochrane Central Register of Controlled trials (CENTRAL), Issue 12, 2012; MEDLINE (via OVID) to update 20130329; EMBASE (via OVID) to week 201313 and PsycINFO (via OVID) to update 20130401. See the Tobacco Addiction Group Module in the Cochrane Library for full search strategies and lists of other resources searched.

Data collection and analysis

Selection of studies

One review author (LFS or JHB) identified potentially eligible trials for inclusion. We included all studies that randomly assigned people already abstaining from smoking. In studies that randomly assigned smokers before quitting, almost all behavioural interventions include relapse prevention components. We included only studies that explicitly identified in their titles or abstracts a focus on relapse prevention or maintenance. In addition, we included all studies that tested the effect of extended contact by telephone after an initial intervention, whether or not relapse prevention was highlighted. Unless abstainers were randomly assigned, we did not include studies of exercise or studies of aversive smoking because the interventions used are similar, whether described as relapse prevention or not, and are covered in separate Cochrane reviews (Hajek 2001a; Ussher 2012). We excluded most interventions for hospitalised participants because trials generally do not describe whether participants are already abstinent or not, and interventions typically contain a mixture of cessation and relapse prevention components. All studies of this type are also covered by a separate review (Rigotti 2012).

Data extraction and management

One review author (LFS or JHB) identified potentially eligible trials for inclusion and extracted data. A second review author (TL) checked data extracted for included or borderline studies and then, together with the third review author (PH), decided on study inclusion and the categorisation of studies into subgroups.

We reported the following trial characteristics in the 'Characteristics of included studies' table.

  • Country and setting in which study was undertaken, including population targeted for recruitment.

  • Methods of randomization, allocation concealment, and blinding.

  • Demographics of participants, including age, sex, baseline cigarette consumption and period of prior quitting if relevant.

  • Intervention components, including numbers and types of contacts and periods of contact.

  • Control condition(s).

  • Outcome, including length of follow- up, definition(s) of cessation used in review and any other measures used.

  • Validation of self-reported smoking status, including method used and cut-off point for biochemical validation.

Assessment of risk of bias in included studies

In the 2013 update, we assessed all included studies for risk of bias using the most recent Cochrane tool. We assessed each study's risk of bias on five domains: random sequence generation; allocation concealment; blinding of participants and personnel; blinding of outcome assessment; and incomplete outcomes data. We noted other risks of bias where relevant, and studies that provided insufficient information on which to make judgements were coded as 'unclear' in the relevant domains. Studies were considered to be at high risk of attrition bias (incomplete outcomes data) when lack of information meant that we were unable to include post-randomization dropouts in our denominators, or when less than 50% of participants were followed up at six months or longer. Had studies of pharmacotherapies not used placebo, we would have considered these to be at high risk of performance bias (blinding of participants/personnel), but we did not require blinding of participants in behavioural interventions. We judged studies to be at high risk of detection bias (blinding of outcomes assessors) when no biochemical validation was used and the intervention arm received more face-to-face contact than the control arm, as we considered differential misreport a possibility in these cases.

Measures of treatment effect

The primary outcome was the number of quitters at the longest follow-up. We used biochemically validated cessation in preference to self-report where available. When given a choice, we included continuous abstinence in preference to point prevalence abstinence. Randomly assigned participants who withdrew, were lost to follow-up or failed to provide samples for validation were usually classified as relapsers or continuing smokers. We noted any exceptions to this in the study details, and we estimated whether the choice of denominator was likely to alter the conclusions. If studies reported both strict and more lenient outcomes, we extracted both sets of data and conducted a sensitivity analysis on the pooled results.

Dealing with missing data

In the protocol for this review, we planned to approach authors to ask for additional data about end of treatment quit rates and long-term quit rates in early quitters. In view of the heterogeneity of interventions, timing of assessments and ways of defining abstinence, we decided that additional data, even if suitable and available, would not strengthen the review. We extracted short-term quit rates for trials that did not randomly assign abstainers and considered whether any benefit of relapse prevention intervention was apparent at this point and whether it differed from the long-term effect.

Assessment of heterogeneity

To investigate heterogeneity, we used the I² statistic, given by the formula [(Q - df)/Q] × 100%, where Q is the Chi² statistic anddf is its degrees of freedom (Higgins 2003). This describes the percentage of variability in effect estimates that is due to heterogeneity rather than to sampling error (chance). A value greater than 50% may be considered to indicate substantial heterogeneity. In the event of significant statistical or clinical heterogeneity between trials, we determined not to report pooled estimates.

Data synthesis

We use the risk ratio rather than the odds ratio to summarise individual trial outcomes and to determine estimates of pooled effect. Treatment effects will seem smaller when expressed as risk ratios than when expressed as odds ratios, unless the event rates are very low. For example, if 20 of 100 participants have quit from the intervention group, and 10 of 100 from the control group, the risk ratio is 2.0 [(20/100)/(10/100)], and the odds ratio is 2.25 [(20/80)/(10/90)]. Whilst there are circumstances in which odds ratios may be preferable, there is a danger that they will be interpreted as if they are risk ratios, making the treatment effect seem larger than it is (Deeks 2002). We estimated a pooled weighted average of risk ratios using a Mantel-Haenszel fixed-effect method with 95% confidence intervals. Had a study reported an odds ratio corrected for clustering or baseline imbalance, and were we unable to derive a risk ratio, we planned to pool odds ratios for trials in the same subgroup of a comparison using the inverse variance method to check whether there was an effect on the results.

Subgroup analysis and investigation of heterogeneity

We planned not to pool results from trials that randomly assigned abstainers with results from those that randomly assigned smokers, but we made two exceptions to this: see discussion of Killen 2006 and Wetter 2011 in Description of studies. Our predefined subgroups were based on the type and intensity of intervention. We separated studies in which contact time was matched from those in which relapse prevention included a longer duration of contact.

Other prespecified subgroups included trials in spontaneous quitters such as pregnant women and in smokers seeking smoking cessation treatment. We added further subgroup analyses to distinguish between longer (longer than four weeks) and shorter intervention and control durations. We also considered subgroup analyses for 'skills' and social support studies. This replaced our planned subgroup division based on the format of the intervention (group versus individual) as this was more relevant within the available sample of studies.

Results

Description of studies

We identified 63 studies for inclusion, 9 of which were new for the 2013 update. One paper reported two studies, each of which had multiple arms relevant to different comparisons (Buchkremer 1991 1; Buchkremer 1991 2), and six trials had subgroups or factorial designs that contributed to different sections or subgroups (Curry 1988; Killen 1990; Fortmann 1995; Schmitz 1999; Covey 2007; Croghan 2007). Two studies did not specifically describe the intervention as involving relapse prevention. Two were similar to an included study by the same group (Hall 1987; Klesges 2006), and one randomized abstainers (Hajek 2002). Most studies were conducted in the United States. Details of each included study can be found in the Characteristics of included studies table.

We describe and analyse separately those studies that randomly assigned people who had already stopped smoking and those that randomly assigned people who were still smoking. We made two exceptions to this scheme: we consider Killen 2006 along with other extended pharmacotherapy trials, and we consider Wetter 2011 along with other trials testing behavioural adjuncts to cessation programmes.

Details of 37 excluded studies are listed in the Characteristics of excluded studies table. The main reasons for exclusion were follow-up of less than six months or not meeting our criteria for a study of relapse prevention. We also identified three ongoing studies, details of which can be found in the Characteristics of ongoing studies table. Two of these test behavioural interventions (Jung 2010; Williams 2011) and the third tests the efficacy of extended treatment with varenicline in people with schizophrenia (NCT00621777).

Section 1. Studies randomly assigning abstainers

Forty-one studies included people who had already stopped smoking.

We considered separately studies involving unaided abstainers who had stopped smoking where it is prohibited, due to factors such as pregnancy, hospital stay, or military training. Another group of studies concerned ex-smokers recruited from the general population.

We divided studies into those assessing behavioural interventions and those assessing pharmacotherapy. We classified behavioural interventions into intensive and less intensive categories. Intensive interventions involve repeated face-to-face contact, usually aimed at teaching clients to identify tempting situations and to apply a range of coping skills and cognitive strategies assumed to be of help in resisting relapse. Less intensive interventions usually attempt to teach these skills via written materials and may involve one brief face-to-face session and telephone contacts. In the event that any trials used telephone contacts of sufficient frequency and duration to be considered an intensive intervention, we would have investigated the sensitivity of our findings to alternative categorisation.

Behavioural interventions in special populations

Eighteen studies focused on populations other than smokers seeking treatment, including pregnant and postpartum women, hospital inpatients and army recruits. Most used minimal face-to-face contact and relied primarily on written materials and/or phone calls. Studies examining more intensive interventions had very small sample sizes. No study in this group used a pharmacological intervention.

Eight studies among pregnant women (Severson 1997; McBride 1999; Hajek 2001; McBride 2004; Pbert 2004; Morasco 2006; Ruger 2008; Hannöver 2009) and one study in hospital inpatients (Schmitz 1999) included both current smokers and recent ex-smokers but analysed the two subgroups separately and so were eligible for inclusion here. Two studies randomized smokers and recent ex-smokers during pregnancy and evaluated the effects of postpregnancy interventions on women from both groups who did not smoke at delivery (McBride 1999; McBride 2004).

Pregnant and postpartum ex-smokers

Fifteen studies randomized pregnant (Ershoff 1995; Secker-Walker 1995; Lowe 1997; Secker-Walker 1998; McBride 1999; Hajek 2001; McBride 2004; Pbert 2004; Morasco 2006; Ruger 2008; Reitzel 2010) or post postpartum (Severson 1997; Ratner 2000; Van't Hof 2000; Hannöver 2009) ex-smokers to interventions designed to assist them in remaining abstinent throughout their pregnancy and/or after delivery.

Six studies evaluated relatively brief interventions, comprising an initial face-to-face counselling session supported by written materials given out at the session (Secker-Walker 1995; Lowe 1997; Secker-Walker 1998; Hajek 2001), repeated mailings over a period of time (Ershoff 1995), or the addition of a video (Severson 1997). In each case, there was provision for opportunistic support of different intensity at other routine visits. One study provided the initial relapse prevention counselling session and reinforcements at later visits without written pamphlets (Van't Hof 2000). Two studies included no face-to-face contact specific to the intervention but provided a series of phone calls (McBride 2004) or calls and letters, booklets, and newsletters (McBride 1999). One study used a 90-minute psychotherapy session and additional phone calls (Morasco 2006). Two studies evaluated motivational interviewing (Hannöver 2009; Ruger 2008). One study assessed a more intensive postpartum intervention that included a series of eight supportive telephone calls in addition to the initial session and written materials (Ratner 2000). A further study evaluated six telephone-based counselling sessions that included two calls postpartum and four calls up to sixteen weeks postpartum (Reitzel 2010). This was a three-armed study, and participants in the second intervention arm were given two in-person counselling sessions, in addition to telephone counselling. The two intervention arms did not differ in outcomes, hence we combined them in our analysis. Finally, one study randomly assigned clinics to implement a provider counselling and office systems intervention (Pbert 2004). We were unable to extract data from this study in a comparable format to pool with the other studies, so we report them separately.

Hospital inpatients

Two studies randomized hospital inpatients diagnosed with cardiovascular illness who had not smoked from the time of hospital admission. One study evaluated a brief, routine, one-off intervention supported by written materials (Hajek 2002), and the other compared six weekly sessions of skills-oriented relapse prevention with didactic presentations (Schmitz 1999). A third study randomly assigned participants who had quit during or shortly before hospitalisation to receive three telephone calls after discharge; all participants received counselling in hospital (Hasuo 2004).

Military recruits

Three studies provided interventions to smokers undergoing enforced abstinence during armed forces training. Two randomly assigned United States Air Force recruits: Klesges 1999 provided a 50-minute session during training that covered the short-term health consequences, costs and social impact of smoking, and Klesges 2006 provided two one-hour sessions. Conway 2004 randomly assigned naval recruits; in addition to regular smokers, the intervention targeted former, occasional and experimental smokers. Two interventions were tested: (1) written materials mailed in six instalments after the conclusion of training and (2) access to a telephone help line.

Behavioural interventions in unselected populations

Ten studies explored behavioural interventions in general populations of smokers.

Behavioural interventions for unaided abstainers

Five studies randomly assigned participants recruited from local communities.

  • Brandon 2000 and Brandon 2004 recruited volunteers who reported at least one week of abstinence (the average duration of prior abstinence was 16 months in Brandon 2000 and 75 days in Brandon 2004).

  • In Fortmann 1995, volunteers recruited with the help of random digit dialling and incentives were randomly assigned following a 24-hour abstinence.

  • In Killen 1990, volunteers recruited by advertisements were encouraged over the phone to set a quit date and were randomly assigned if they managed to abstain for 48 hours.

  • In Borland 2004, callers to a quitline were recruited into a study a day or two later, and we included only the subgroup of callers who had already quit at this baseline.

All interventions were of relatively low intensity, involving self-help materials or telephone contact.

  • Killen 1990 examined effects of an eight-week self-guided relapse prevention programme based on 16 modules. Participants received the basic module at the first session. After this, another seven modules either selected by participants or assigned randomly were dispensed via weekly mailings over the next seven weeks. The factorial study also included nicotine chewing gum conditions (covered later).

  • Fortmann 1995 evaluated a two-phase self-help relapse prevention programme that included 12 weekly progress reports to be mailed by participants to the programme office. The factorial study also included nicotine chewing gum conditions (covered later).

  • Brandon 2000 compared effects of a single booklet with effects of a partially pro-active telephone helpline, eight booklet mailings, and a combination of helpline and mailings.

  • Borland 2004 compared the provision of tailored advice letters based on telephone assessments with the provision of standard materials only.

  • Brandon 2004 manipulated contact and content by comparing eight booklet mailings over 12 months, the same booklets at a single mailing, eight supportive letters over 12 months, and a single booklet which we treat as the control in the analysis.

Behavioural interventions for assisted abstainers

Seven studies randomly assigned abstaining smokers who had taken part in a formal treatment programme.

  • Powell 1981 randomly assigned abstainers at the end of a five-day programme to a four-week support group, a telephone 'buddy' system, or a no-treatment control.

  • Stevens 1989 recruited smokers who had a quit date one week earlier and were smoking no more than one cigarette in the previous four days. Participants were randomly assigned to three weekly skills training group sessions, three weekly discussion group sessions or a no-treatment control.

  • Razavi 1999 randomly assigned clients abstinent at the end of a three-month treatment with nicotine patch and group support to monthly group meetings focusing on relapse prevention strategies, monthly group meetings run by former smokers offering general support, or to a no-treatment control.

  • Smith 2001 randomly assigned participants eight days after quit date, using stratification based on smoking status, so that those who were abstinent during this week were analysed separately. The two intensive interventions consisted of six 90-minute group sessions spaced over four weeks after the randomization session. They focused on developing cessation skills and negative affect (cognitive-behavioural treatment) or on fostering intrinsic motivation and resolving participant ambivalence (motivational interviewing). The control group did not receive any intervention after the randomization session.

  • Mermelstein 2003 randomly assigned people at the end of a seven-week group behavioural programme to receive tailored counselling calls or non-specific calls from their counsellor. We include only the subgroup of participants who were abstinent at the end of the group meetings.

  • Juliano 2006 was a study of a relapse-sensitive rapid smoking intervention that randomly assigned participants who lapsed in the first 14 days after an intervention that included counselling and bupropion.

  • Mayer 2010 studied participants in workplace cessation programmes. At the end of the programme, abstinent participants were randomly assigned to ten sessions of workplace group counselling or ten sessions of proactive telephone counselling over the course of nine months. This study did not include a control group; therefore it is not included in the meta-analysis. Results are reported narratively later.

Pharmacological interventions
Pharmacological interventions for short-term unaided abstainers

Two studies of nicotine gum randomly assigned participants who had briefly stopped unaided.

  • Killen 1990 randomly assigned participants who stopped unaided for 48 hours to nicotine gum on a fixed or ad lib dosing schedule and included a no-gum control.

  • Fortmann 1995 randomly assigned participants who stopped smoking unaided for 24 hours to nicotine chewing gum and no medication groups. (Both of these factorial studies also included behavioural interventions as discussed above.)

Pharmacological interventions for abstainers following cessation pharmacotherapy

Five studies enrolled people to use pharmacotherapy to aid initial cessation before randomly assigning successful abstainers to pharmacotherapy for maintenance. We also include in this subgroup a sixth study, Killen 2006, in which participants were randomly assigned before starting the quit attempt. The classification of this study is discussed further in Effects of interventions. Six studies evaluated the effects of extended treatment with bupropion. Three of them also included arms that used nicotine replacement therapy (NRT). One study evaluated the effects of extended use of varenicline and one study evaluated the effects of extended use of rimonabant.

  • Hays 2001 used bupropion to aid cessation, and participants were randomly assigned if they had quit for at least one week at the end of seven weeks of treatment. Bupropion or placebo was used for the rest of the year, and participants were followed up for a second year.

  • Hurt 2003 used a nicotine patch to aid cessation, and abstainers were eligible for randomization at the end of eight weeks of patch therapy. Bupropion or placebo was used for six months after randomization and participants were followed up for another six months.

  • Killen 2006 used combination therapy of nicotine patch, bupropion and individual relapse prevention counselling for almost three months, then either bupropion or placebo (after tapering of bupropion) for 14 weeks. Follow-up was at 12 months from quit date. Because participants were randomly assigned at baseline, people who had failed to quit were still eligible for the randomized phase and were included in the denominator.

  • Covey 2007 used a bupropion and nicotine patch combination to aid cessation and randomly assigned abstainers after eight weeks. The double placebo-controlled maintenance phase tested bupropion and nicotine gum in a factorial design. Therapy lasted 16 weeks, and participants were followed up for another six months to assess abstinence 12 months from quit date.

  • Croghan 2007 randomly assigned participants to bupropion, nicotine inhaler or combination therapy for three months. In a second phase, abstainers using a single therapy were randomly assigned to continue the same therapy or receive a placebo for a further nine months, with post-therapy follow-up for a further three months. Abstainers using combination therapy were randomly assigned factorially to bupropion or placebo pill and nicotine inhaler or placebo inhaler.

  • STRATUS-WW 2006 randomly assigned participants to 5 mg or 20 mg rimonabant for ten weeks. In the second phase, abstainers in the 5 mg group were randomly assigned to a further 42 weeks of 5 mg rimonabant or placebo, and abstainers in the 20 mg group were randomly assigned to a further 42 weeks of 5 mg of rimonabant, 20 mg of rimonabant or placebo. Participants were followed up at the end of treatment (52 weeks from baseline).

  • Tonstad 2006 used open-label varenicline for 12 weeks. Abstainers were randomly assigned to varenicline or placebo for a further 12 weeks, and then were followed up for six months for assessment of abstinence 12 months from quit date.

  • Hays 2009 used weekly counselling and nicotine patches to aid cessation in a group of recovering alcoholics. At the end of eight weeks of treatment, participants who had quit for at least the last week of patch therapy were randomly assigned to either bupropion or placebo for 44 weeks.

Section 2. Studies randomly assigning smokers before their quit date

We did not include any studies evaluating pharmacotherapy in this category; all studies assess behavioural interventions. We included two categories of such studies: those that compared time-matched interventions with and without the relapse prevention elements, and those that looked at the effect of extended participant contact. For studies with more than two arms, we included the most intensive versus the least intensive in the main meta-analysis, and we discussed additional differences in the results. We refer to the least intensive intervention as the 'control'.

To evaluate the impact of treatment intensity, we considered separately interventions providing treatment for up to four weeks and interventions providing participant contact for longer than four weeks.

Intervention and control groups matched for contact time

In ten studies, intervention and control conditions were matched for the amount of contact. (Some studies also compared a longer intervention, in which case the relevant arms are compared in the next category.) Eight used a group format for behavioural intervention (Hall 1984; Davis 1986; Curry 1988; Emmons 1988; Buchkremer 1991 1; Buchkremer 1991 2; Becona 1997; Schroter 2006) and two used an individual counselling format (Niaura 1999; Schmitz 1999). Three provided pharmacotherapy in all treatment conditions (Emmons 1988; Buchkremer 1991 1; Buchkremer 1991 2). In one study, a factorial design was used to test nicotine gum against no gum (Niaura 1999).

The components used for relapse prevention were varied.

  • Hall 1984 was a factorial study. The arms comparing two variants of aversive smoking are combined in this analysis. In six of the 14 sessions, the relapse prevention (RP) group received relaxation and relapse prevention skills training and reviewed the cost of smoking and the benefits of abstinence, while the control group met for general discussion.

  • Davis 1986 compared three six-session treatments (i.e. active skills training, discussion of high-risk situations (not shown in graphs), and a standard programme). Only 45 participants were included in the study.

  • In one arm of a factorial study, Curry 1988 compared two programmes in a self-help format: one using a skills-oriented relapse prevention training permissive to slips, and the other stressing absolute abstinence. The other arm compared these two approaches delivered in a format of eight weekly group sessions, where the absolute abstinence approach also included gradual reduction and a quit date two weeks later than in the relapse prevention group. The two study arms are treated separately.

  • Emmons 1988 compared two programmes with different numbers of sessions across the same period of time, both accompanied by nicotine gum. The relapse prevention programme consisted of eight weekly sessions focused on coping with high-risk situations, cognitive behavioural strategies and role-play. The 'Broad Spectrum' behavioural programme consisted of 12 sessions that focused on strategies for dealing with cravings and weight control, with quitting preceded by nicotine fading over three weeks.

  • Two trials by Buchkremer and colleagues explored a variety of behavioural components, as well as different dosing schedules, for the nicotine patch. The programme consisted of nine weekly sessions with a target quit date after six weeks of gradual reduction. Relapse prevention components including role-play were included in one intervention, and this was compared with a control of the same length (Buchkremer 1991 1). In a second study, an alternative relapse prevention approach was used; the programme was modified to reach total abstinence after four weeks, and behaviour therapy techniques such as covert sensitisation and thought-stopping were added. As the differences were relatively small, we combined the two relapse prevention programmes (Buchkremer 1991 2).

  • Becona 1997 compared eight-week behavioural treatment programmes with and without a relapse prevention problem-solving component.

  • Niaura 1999 tested imaginary cue exposure as an addition to individual cognitive behavioural treatment. All groups had five postquit sessions, and we have included them in the matched contact control group, although the duration of both control conditions was different. In a factorial design, a nicotine gum condition and a no-gum condition were compared.

  • Schmitz 1999 used a sample of women with cardiac risk and compared six sessions of skills-oriented relapse prevention with six sessions of didactic presentations on cardiac risk and the benefits of quitting.

  • Schroter 2006 compared six sessions that included components such as role-playing, coping responses to high-risk situations and self-awareness with a standard behavioural cessation programme that focused on positive changes attained through abstinence.

Intervention and control arms not matched for contact time or duration

Almost all smoking cessation studies that compare more and less intensive treatments include some intervention to prevent relapse. We included only trials that specified relapse prevention as an explicit focus of the intervention in the title or abstract. We did not include studies that offered treatment proactively to special populations such as pregnant or hospitalised smokers because all trials using these groups provide some relapse prevention input within the active treatment arm, and they are covered in separate meta-analyses. When studies had three or more treatment conditions, the main analyses compare the most and least intensive interventions.

Behavioural interventions
Varying intensity of face-to-face treatment

Seven studies compared longer and shorter programmes. The relative intensity of the common cessation programme and of the additional relapse prevention component was variable. We subgrouped studies according to whether the control group received more than four sessions.

  • Killen 1984 provided nicotine gum and one-week intensive behavioural treatment, which included relapse prevention components plus seven further brief visits, and compared groups with and without two additional group sessions and optional drop-in visits. A group with no gum was also included but was not used in our analysis.

  • Brandon 1987 treated a sample of smokers in six sessions over two weeks and compared a group receiving no further treatment with a group receiving four additional relapse prevention sessions. Another arm with a rapid puffing component is not covered in this review.

  • Hall 1987 combined nicotine or placebo gum with 5 or 14 sessions, and the more intensive treatment also contained a larger relapse prevention component.

  • Buchkremer 1991 1 tested the addition of three booster sessions six months after the basic nine-session programme and a programme with relapse prevention components. All groups received nicotine patches.

  • Shoptaw 2002 studied smokers treated for heroin dependence and compared the nicotine patch combined with 12 weeks of brief visits with the additions of a behavioural programme that included relapse prevention and mood management, a contingency management programme in which participants were paid for abstinence, and a combination of the latter two.

In two studies, control groups were offered four or fewer sessions.

  • Hall 1985 combined nicotine gum with four educational sessions over three weeks or a behavioural treatment that included relapse prevention components provided in 14 sessions over eight weeks. (A behavioural treatment-only group is not included here.)

  • Lifrak 1997 combined nicotine patch treatment with three supportive sessions with a nurse over nine weeks or with 16 relapse prevention sessions with a behavioural therapist over 16 weeks.

Extended contact using proactive phone calls

Two studies tested extended contact via proactive phone calls. One study (Lando 1996) provided group-based behavioural therapy for eight weeks and compared a group receiving no further treatment with a group receiving proactive calls 1, 8 and 11 months later. The second study (Segan 2011) randomly assigned callers to the Victoria, Australia, quitline to four to six additional calls explicitly designed to prevent smoking relapse and compared this with a control group with no additional calls. We excluded other studies that tested the use of telephone counselling as an adjunct (add-on) to nicotine replacement therapy because they did not describe the intervention as relapse prevention, and most of the behavioural support was provided during the period of intended pharmacotherapy (i.e. not extending the overall duration of treatment).

Access to additional web-based support

One study (Japuntich 2006) provided bupropion and brief individual counselling to all participants. The intervention consisted of internet access to the Comprehensive Health Enhancement Support System for Smoking Cessation and Relapse Prevention (CHESS SCRP) for 12 weeks.

Additional computer-delivered intervention

One study (Wetter 2011) tested the addition of computer-delivered treatment. All participants were provided with six weeks of nicotine patch therapy, five group counselling sessions and ecological momentary assessment (EMA) procedures for one month post quit date. In addition to the EMA, the intervention arm received computer-delivered treatment on palmtop computers for one month post quit date, consisting of three modules.

Other adjuncts

Two studies evaluated other adjuncts to cessation programmes. In van Osch 2008, participants in a national Quit and Win contest received computer-tailored cessation advice and telephone counselling for one month post quit date. The intervention and control arms received the exact same programme, but in the intervention arm, participants were asked to formulate three coping plans when completing the baseline survey. In Sheffer 2010, quitline callers were randomly assigned to standard quitline service or to standard quitline service plus eight printed self-help booklets aimed at relapse prevention. This was a quasi-randomized trial with significant baseline imbalances; findings are reported narratively later.

Combined behavioural and pharmacological interventions

One study tested extended treatment with counselling and NRT (Joseph 2011). All participants were provided with NRT and five telephone calls over four weeks. In the intervention arm, participants received extended telephone counselling and NRT for a further 48 weeks. The control arm received one additional call at eight weeks and no additional NRT.

Risk of bias in included studies

As seen in Figure 1, most studies were judged to be at unclear risk of selection bias and at low risk of performance, detection (blinding) and attrition bias. Details on risk of bias judgements for each study can be found in Characteristics of included studies. In the absence of significant findings in meta-analysis subgroups or evidence of heterogeneity, we did not attempt to explore any influence of risk of bias on outcomes.

Figure 1.

Sample size

Many trials were small and therefore had limited power to detect realistic differences in quit rates, especially in the group that randomly assigned smokers before the quit date.

Study design

Studies randomly assigning successful end-of-treatment quitters provide the most straightforward test of relapse prevention interventions designed for clinical practice (see Discussion ). Seven studies of pharmacological treatments used this approach, but only three studies of behavioural treatments randomly assigned participants who were abstinent after more than one week of treatment (Razavi 1999; Mayer 2010; Mermelstein 2003).

Definition of smoking cessation

All studies were required by our inclusion criteria to report smoking status a minimum of six months from the start of the intervention. In the case of studies that randomly assigned smokers before quitting, this could have been from the quit date. Some studies timed follow-up from the end of treatment. Seven trials (Emmons 1988; Schmitz 1999; Van't Hof 2000; Japuntich 2006; Juliano 2006; Reitzel 2010; Sheffer 2010) had six months' follow-up, and all others had a longer follow-up period from the start of intervention. Some studies did not provide a definition of abstinence (Powell 1981; Becona 1997; Klesges 1999; Hasuo 2004), and most others reported a point prevalence rather than a sustained measure of abstinence.

Allocation

All but one study stated that allocation was random, but few reported the methods of sequence generation and allocation in sufficient detail to be certain that the risk of bias was minimised, hence most were rated as unclear in these domains.

Nine studies used cluster-randomized designs. In the three among military recruits (Klesges 1999; Conway 2004; Klesges 2006), allocation was determined by training group, and selection bias was unlikely. In a further three, allocation was by midwife (Hajek 2001; Pbert 2004) or paediatric practice (Severson 1997), and selection bias in the subsequent enrolment of participants might have been possible. Two of the cluster-randomized trials reported that correlation between outcomes in individuals in the same cluster was small, so that reporting of individual outcomes was acceptable. These two trials also had high loss to follow-up, although there was no evidence of differential loss between arms. One study in pregnant women (Pbert 2004) randomly assigned six clinics, but one control clinic withdrew because of poor participant recruitment. Of the remaining five sites, two contributed more than 50% of the participants. An appropriate method of analysis was used; because of the small number of clusters, differences between crude effects and corrected estimates were noted, and we did not attempt to incorporate the results into a meta-analysis. One small study ran an intervention group and a control group in each of four workplaces. No information was provided on recruitment and participant blinding procedures (Schroter 2006). One quasi-randomized trial of quitline callers sent printed self-help materials aimed at relapse prevention to all quitline callers who ended treatment within a given six-week period (Sheffer 2010). Callers to the quitline during the six weeks preceding and following the given six-week period were used as a control group. One quasi-randomized trial of quitline callers sent printed self-help materials aimed at relapse prevention to all quitline callers who ended treatment within a given six-week period (Sheffer 2010). Callers to the quitline in the six weeks preceding and following the given six-week period were used as a control group.

Blinding (performance bias)

Most studies did not provide sufficient detail to allow evaluation of risk of performance bias and hence were judged to be at unclear risk in this domain. Eighteen studies provided details of blinding procedures sufficient to rate them at low risk of bias in this domain (or, in the case of behavioural interventions where blinding of participants was not possible, where other study characteristics meant that performance bias was judged to be unlikely). Five studies were judged to be at high risk of performance bias: two studies testing NRT did not provide placebo to the control arms (Killen 1984; Hall 1985); in two studies of behavioural interventions, neither participants nor providers were blinded, and control participants were aware that the intervention arm was receiving additional treatment (Juliano 2006; Reitzel 2010); and in a fifth study, blinding was broken (Segan 2011).

Validation of self-reported abstinence (detection bias)

Biochemical validation of most or all self-reports of abstinence was reported for most studies. Fourteen studies did not attempt any validation (Powell 1981; Severson 1997; Klesges 1999; Van't Hof 2000; Mermelstein 2003; Borland 2004; Conway 2004; Klesges 2006; Schroter 2006; van Osch 2008; Hannöver 2009; Sheffer 2010; Joseph 2011; Segan 2011), but in some other cases, samples were not collected from all participants, were not collected at long-term follow up or were not used to correct self-reports. In one unpublished study, it was unclear whether results were validated (STRATUS-WW 2006), and another study reported the use of biochemical validation but not the cut-off value or the level of misreport (Ruger 2008). One study noted greater deception amongst intervention group participants than amongst those in the control condition (Pbert 2004).

In studies of behavioural smoking cessation interventions, lack of biochemical validation of self-reported smoking status risks the introduction of significant bias. Participants who received more intensive care can be expected to be trying harder to please their advisors and report ‘good news’. When the intervention group received more face-to-face contact than the control group and the results were not biochemically validated, we judged studies to be at high risk of detection bias.

Incomplete outcome data

Another risk of bias specific to smoking cessation studies concerns excluding participants lost to follow-up from the analysis or imputing their outcomes as if their loss to follow-up was independent of outcome. This is because in smoking cessation treatments, patients who fail in stopping smoking may feel embarrassed and may find further participation unhelpful, while those who are successful may be more likely to stay in touch. Treating those lost to follow-up as still smoking is likely to be a reasonable assumption, but sometimes the actual figures are not available, or loss to follow-up is such that most participants have not provided data, or many more participants have been followed up in one arm than in another. When these limitations were present, studies were judged to be- at unclear or high risk of attrition bias.

Most studies reported low or moderate losses to follow-up in sufficient detail to be judged at low risk of bias in this domain. One study was judged to be at high risk of attrition bias (van Osch 2008) because loss to follow-up was high in both arms (less than 40% of participants followed up at seven months); the study authors cautioned that this limited the validity of the results. A further six studies were judged to be at unclear risk of bias in this domain, as the studies did not report results in sufficient detail to permit counting of all participants lost to follow-up as continuing smokers in our analyses (Brandon 2000; Buchkremer 1991 1; Buchkremer 1991 2; Davis 1986; Emmons 1988; Hannöver 2009).

Effects of interventions

See: Summary of findings for the main comparison Behavioural interventions for assisted abstainers; Summary of findings 2 Pharmacotherapy for assisted abstainers

Section 1. Trials in abstainers

Behavioural interventions in special populations
Pregnant and postpartum ex-smokers

Pooled results from eight trials of interventions in pregnancy did not demonstrate a significant benefit at the end of pregnancy (n = 1523, risk ratio [RR] 1.04, 95% confidence interval [CI] 0.98 to 1.11, I² = 0%; Analysis 1.1). Twelve studies included follow-up during the postpartum period. We also failed to detect any significant benefit among this group of studies, overall or in subgroups, according to timing of intervention, with the confidence interval narrowly missing significance (n = 3524, RR 1.08, 95% CI 0.99 to 1.19, I² = 0%; Analysis 1.2). One further study that we could not include in the meta-analysis did not detect any significant effect of intervention on spontaneous quitters at delivery; the postpartum non-smoking rate was higher in the usual care group (Pbert 2004).

Hospital inpatients

There was no evidence of a significant benefit of intervention in hospitalised patients who had not smoked in hospital, based on pooled results from three studies (Schmitz 1999; Hajek 2002; Hasuo 2004) (n = 667, RR 0.94, 95% CI 0.78 to 1.13, I² = 0%; Analysis 2.1).

Military recruits

We did not display results graphically or pool results because denominators were unclear and reported results were corrected for clustering. In all three trials, the period of enforced abstinence did give rise to a higher quit rate than the spontaneous rate expected in these populations of young smokers, but only Klesges 2006 reported a statistically significant effect. With adjustments for clustering and predictors, the odds ratio for continuous abstinence at one year was 1.23 (95% CI 1.07 to 1.41). Crude abstinence rates were 15.47% versus 13.74%, so the absolute effect was small. The earlier study (Klesges 1999) reported a significant intervention effect only in a subgroup of people who had not been planning to remain quit after the end of training. The study in female naval recruits (Conway 2004) provided the intervention after the end of training and did not detect an effect of mail or phone intervention; less than 3% of participants called the helpline for counselling.

Behavioural interventions in unselected populations
Behavioural interventions for unaided abstainers

We found no evidence of a benefit of interventions to prevent relapse in people who had initially quit unaided (Killen 1990; Fortmann 1995; Brandon 2000; Borland 2004; Brandon 2004) (n = 3561, RR 1.08, 95% CI 0.98 to 1.19, I² = 1%; Analysis 3.1). All five studies used low-intensity self-help interventions, although in one, the materials were individually tailored on the basis of information collected via telephone questionnaires, and this trial suggested a borderline effect (Borland 2004).

Behavioural interventions for assisted abstainers

We detected no long-term benefit of skills-based interventions in preventing relapse in five studies in which abstaining smokers were randomly assigned after they had taken part in a formal treatment programme (Powell 1981; Stevens 1989; Razavi 1999; Smith 2001; Mermelstein 2003) (n = 1462, RR 1.00, 95% CI 0.87 to 1.15, I² = 56%; Analysis 4.1). This meta-analysis compared the most intensive intervention with the least intensive control in the trials with more than two arms. Using different comparison conditions did not change the conclusion.

One small trial (Juliano 2006) offered up to three sessions of rapid smoking to participants who lapsed within 14 days of a cessation intervention. No participants (0/20) were abstinent at six months in the intervention group, and only one participant was abstinent in the control group (1/14). No evidence of a short-term benefit was found. This supports the observation that people who cannot maintain abstinence in the early days of a quit attempt are at particularly high risk of relapse and does not support the use of rapid smoking as a relapse prevention measure.

One trial compared workplace group counselling with proactive phone counselling post-cessation and did not detect a significant difference between the two at 12 months (workplace versus phone, RR 1.07, 95% CI 0.88 to 1.31; analysis not shown, Mayer 2010).

Pharmacological interventions
Pharmacological interventions for short-term unaided abstainers

Pooled results of two large trials of nicotine gum detected a small effect (Killen 1990; Fortmann 1995) (n = 2261, RR 1.24, 95% Cl 1.04 to 1.47, I² = 56%; Analysis 5.1). In both of these studies, the period of unassisted abstinence was short, and these studies are distinct from the next group, in which a more extended period of abstinence was required before the relapse prevention phase was initiated.

Pharmacological interventions for abstainers after cessation therapy

Pooling two studies of NRT (Covey 2007 using gum and Croghan 2007 inhaler, both with factorial designs entered separately) did not reveal a significant long-term effect (n = 553, RR 1.04, 95% CI 0.77 to 1.40, I² = 0%; Analysis 6.1). This contrasts with the two studies discussed in the previous section. It is worth noting that compliance with oral NRT was low, and that one study replaced the initial patch treatment with 2 mg gum (Covey 2007).

The estimated effect of extended therapy with bupropion based on six studies narrowly misses statistical significance (n = 1697, RR 1.15, 95% CI 0.98 to 1.35, I² = 0%; Analysis 6.2). Whilst there was no evidence of statistical heterogeneity, some clinical heterogeneity was noted in the intervention used for the cessation induction phase, the duration of treatment and the duration of follow-up after cessation of medication.

Figure 2

Figure 2.

Forest plot of comparison: 6 Pharmacotherapy for assisted abstainers, outcome: 6.2 Bupropion versus placebo. Cessation at least 6 m after end of therapy and at least 12 m after quit date.

Two studies (Covey 2007; Croghan 2007) allow a comparison between combination therapy of bupropion and NRT versus neither. No significant benefit was detected (n = 243, RR 1.18, 95% CI 0.75 to 1.87; Analysis 6.3), and some evidence of heterogeneity was found (I² = 66%).

A single study (Tonstad 2006; n = 1210) detected a significant benefit of extended varenicline (RR 1.18, 95% CI 1.03 to 1.36; Analysis 6.4).

One further study (STRATUS-WW 2006; n = 1017) detected a significant benefit of extended treatment with rimonabant (RR 1.29, 95% CI 1.08 to 1.55; Analysis 6.5). Rimonabant is not licensed for use in any country, and its manufacturers are no longer supporting its development because of safety concerns (Cahill 2013).

Section 2. Studies randomly assigning smokers before their quit date

Intervention and control groups matched for contact time

We found that no benefit was derived from the use of specific relapse prevention components in group or individual format interventions; this finding was based on the results of 10 trials (n = 872, RR 0.91, 95% CI 0.73 to 1.13; Analysis 7.1). No evidence of heterogeneity was noted (I² = 11%). All but one (Niaura 1999) of the studies involved treatment contact for longer than four weeks; therefore, we did not conduct a subgroup analysis by treatment duration. Most trials used a skills training approach, so we did not conduct a subgroup analysis by treatment type.

One study with two arms comparing different versions of a self-help programme did not detect a difference in quit rates (Curry 1988, RR 1.52, 95% CI 0.67 to 3.46; Analysis 7.2).

Intervention and control arms not matched for contact time or duration
Behavioural interventions
Varying intensity of face-to-face intervention

We detected no effect of relapse prevention in seven trials that tested extended face-to-face contact (Killen 1984; Hall 1985; Brandon 1987; Hall 1987; Buchkremer 1991 1; Lifrak 1997; Shoptaw 2002) (n = 699, RR 1.01, 95% CI 0.80 to 1.27, I2 = 4%; Analysis 8.1). There was no evidence of differences between subgroups based on the number of control group contacts.

Extended contact using proactive telephone calls

Two trials (Lando 1996; Segan 2011) did not detect a benefit of providing extended contact by telephone (RR 1.06, 95% CI 0.90 to 1.23; Analysis 9.1.1). Statistical heterogeneity was low (I² = 0%) despite differences in the initial cessation programme: In Lando 1996, participants received additional calls after an intensive eight-week group programme, whereas in Segan 2011, additional calls were tested as an adjunct to standard quitline treatment.

Access to additional web-based support

One trial (Japuntich 2006) did not detect a benefit of providing support via the Internet as an adjunct to bupropion and brief counselling (RR 1.27, 95% CI 0.70 to 2.31; Analysis 9.1.2). Nor was an effect detected amongst a subgroup of participants who were quit at two-day follow-up, a more specific test of relapse prevention. Frequent users were more likely to remain abstinent when controlling for other potential predictors of success.

Additional computer-delivered intervention

One trial (Wetter 2011) did not detect a benefit of adding palmtop computer treatment to EMA for one month post-cessation (RR 0.93, 95% CI 0.64 to 1.35; Analysis 9.1.3).

Other behavioural adjuncts

A trial evaluating the impact of asking participants of a Quit and Win contest to formulate coping strategies in advance also did not detect an effect (RR 1.27, 95% CI 0.97 to 1.67; Analysis 9.1.4; van Osch 2008). A quasi-randomized trial (Sheffer 2010) tested the provision of eight "Forever Free" booklets (aimed at relapse prevention) to quitline callers. Significant baseline imbalances were noted between groups. The authors report that, when adjusted for age, amount of treatment content, number of patches dispensed during cessation phase, and stress level, the odds of achieving abstinence at six months as the result of "Forever Free" booklets were not statistically significant (OR 1.15, CI 0.78 to 1.67).

Combined behavioural and pharmacological interventions

One study (Joseph 2011; n = 433) that tested extended therapy with both NRT and proactive telephone counselling did not detect a significant effect at 18 months (RR 1.28, 95% CI 0.94 to 1.75; Analysis 9.2).

Discussion

Summary of main results

In this review, we failed to detect a clinically significant effect of existing behavioural 'relapse prevention' methods for people quitting smoking. However, several factors may temper this disappointing conclusion. The included studies had both methodological and content limitations; the overall GRADE quality score was very low (Summary of findings for the main comparison). Most studies reported only point prevalence abstinence, and only a small number of studies included in this review had adequate sample sizes to detect the expected effects. Most studies that randomly assigned recent abstainers focused on brief or written interventions rather than on more intensive treatments, and most of the existing studies tested only one particular treatment approach.

Results for some pharmacotherapies were more encouraging, with the quality of evidence ranging from low to moderate (Summary of findings 2). In the trial of extended varenicline use (Tonstad 2006), 63% of participants who quit after 12 weeks on varenicline had relapsed by the end of a year, compared with only 56% of those who received a further 12 weeks of therapy. The study of rimonabant also detected a significant effect in favour of the intervention, but this drug has been withdrawn from the market because of concerns about its safety. The six studies of bupropion, when combined, narrowly failed to reach significance; none yielded a significant result on their own, and the two comparisons of bupropion plus NRT versus double placebo were also negative. This makes it unlikely that any clinically significant effect was missed.

In discussing the further implications of this review, we first comment on the technical aspects and limitations and attempt to make some methodological recommendations for future work in this area. We then discuss some of the conclusions pertaining to different treatment formats.

Inclusion and exclusion of studies

Identifying criteria for including studies in this review was difficult. We included all studies that randomly assigned abstainers, as these provide the best test of interventions aimed at maintaining abstinence. Studies randomly assigning smokers before quitting presented a challenge. Although such studies may be described as studies of relapse prevention, they usually test primarily smoking cessation interventions, with interventions aimed at preventing relapse added to the treatment programme but not analysed separately. One of the problems involved in considering the inclusion of smoking cessation studies with a specified relapse prevention component is that they were sometimes similar in design to other studies that did not specifically mention relapse prevention in their title or abstract but used virtually identical methods. In our initial analyses, we included a wider group of studies (e.g. Goldstein 1989; Zelman 1992; Hall 1994; Hall 1996; Brown 2001), but in the end we decided to restrict the analysis of studies randomly assigning smokers to those that mentioned relapse prevention explicitly. The results of the review are not affected by this decision, as the excluded studies were also small and did not show significant treatment effects. We also excluded a small number of studies that randomly assigned smokers before quitting and that explicitly included relapse prevention or maintenance but concerned smoking cessation interventions that are already covered by three other Cochrane reviews: exercise (Ussher 2012), aversive smoking (Hajek 2001a), and interventions for hospitalised smokers (Rigotti 2012).

The negative results of the individual studies are fairly consistent, and it is unlikely that using alternative inclusion criteria would lead to different conclusions; however, identifying appropriate studies in this challenging area is difficult. Possible limitations of the review are that we failed to identify relevant research and that we did not pool studies appropriately. We think it is unlikely that large effects have been missed in the trials so far conducted, but in some cases the studies were too small to allow detection of moderate effects.

The two trial designs according to the timing of randomization

The key methodological feature of existing attempts to evaluate relapse prevention interventions concerns the time when participants were randomly assigned (i.e. before or after they stopped smoking).

The main logical argument in favour of randomly assigning smokers before they stop smoking is that much relapse prevention advice could be relevant even in the very first stages of quitting smoking. On the practical side, although it is relatively easy to attract smokers to start an experimental treatment, the samples would be much smaller if only those abstinent at the end of treatment were enrolled. However, combining cessation and relapse prevention reduces the power to detect specific relapse prevention effects. The primary outcome variable is normally the abstinence rate at follow-up, and it is difficult to differentiate any effects that the intervention may have had on the initial smoking cessation from effects on preventing relapse in smokers who were initially successful. The initial success or failure is likely to be determined by a number of intervention and participant variables other than the relapse prevention component, which is usually only a small part of the overall programme. One way to resolve this problem could be to focus the analysis on the initial successes only. However, none of the existing studies used this approach, and the published data usually do not include sufficient details to allow survival analysis. Even if relapse rates for initially successful abstainers were available, the relapse prevention effect would be difficult to interpret when comparison groups have different short-term cessation rates.

Randomly assigning only those smokers who have made a successful quit attempt represents a stronger study design. As cessation interventions are segregated from relapse prevention interventions, the results cannot be skewed by uneven initial cessation rates, any relapse prevention effects are more likely to be detected and the results are easy to interpret. On the downside, this approach requires greater effort to recruit sufficient samples. Among existing studies of behavioural treatments using this approach, most have used spontaneous abstainers such as pregnant women. In fact, of the eligible studies of behavioural methods for relapse prevention, only two studies randomly assigned smokers abstinent at the end of an initial treatment episode (Razavi 1999; Mermelstein 2003), and three randomly assigned smokers abstinent five to eight days after their quit day (Powell 1981; Stevens 1989; Smith 2001).

The difference between the initial smoking cessation and later relapse prevention treatment is much clearer in pharmacotherapy, and all drug trials but one used this more robust paradigm.

The studies that randomly assigned abstainers varied considerably in the periods of time for which participants had already abstained from smoking (i.e. from 24 hours to 16 months). There seems to be broad agreement on the conceptual distinction between 'stopping smoking' and 'staying quit' and on the common understanding of the concept of relapse, but accepted operational definitions are lacking, although some suggestions have been made (Ossip-Klein 1986). It seems clear that abstinence for a period of time close to inter-cigarette intervals, or overnight abstinence, does not constitute cessation of smoking, and that a return to smoking after several weeks of total abstinence can be classified as a relapse. However, common behaviours such as abstinence for 24 hours or smoking only a few cigarettes every few days, become more difficult to classify. Little consensus has been reached on what amount of smoking after what type of smoking restraint over what period of time represents a relapse as opposed to the initial failure to stop smoking. Ideally, future relapse prevention studies should follow the example of existing drug trials and should use sufficiently long periods of no smoking and sufficiently strict definitions of the initial abstinence and outcome to avoid areas of contention.

Some methodological recommendations

The ideal study of a relapse prevention intervention aimed at complementing existing treatments for smokers seeking help would randomly assign smokers who were abstinent continuously and completely for at least four weeks. An appropriate outcome measure would be continuous lapse-free abstinence of at least six months when the intervention was aimed at avoiding lapses, but some lapses would have to be allowed when the intervention was aimed at helping patients to cope with lapses should these occur. General agreement has been reached that for dependent smokers seeking treatment, becoming an occasional smoker is usually not an option, and for a long-term success, any lapses would have to cease eventually. It would seem sensible to allow lapses over a limited 'period of grace' (e.g. three or even six months), followed by at least six months of lapse-free abstinence. Most studies in this review were seriously underpowered, using 15 or 20 participants per condition. Future research needs to acknowledge that any effects are likely to be small, and that large samples will be needed to avoid type 2 errors.

Interpreting the review results

The 41 studies that randomly assigned abstainers represent the main interpretable body of data in this field. The results of both special population studies and studies of smokers seeking treatment suggest that behavioural brief interventions and interventions relying on written materials, mailings and telephone contact are ineffective for relapse prevention. It may be important to note that more intensive approaches were examined in only a handful of studies, and some were too small to allow detection of any realistic effect. Although intensive interventions in this area need to resolve the likely problems related to intervention costs and patient attendance, further work on such treatments may be needed.

Rates of abstinence were highly variable across studies because of such factors as the population studied, the intensity of any cessation intervention provided, the period for which abstinence had already been maintained, the length of follow-up and the definition of cessation. Because of obvious problems with comparisons of success rates across studies (Hajek 1994), we did not discuss results in terms of the absolute abstinence rates achieved.

With regard to the contents of the behavioural interventions, the negative results concern primarily the traditional skills-based approach, which holds a virtual monopoly in this field. It remains a possibility that the original concept is valid (i.e. that patients can benefit from being taught how to identify tempting situations), and that effective strategies for coping with such situations can also be taught. If this is the case, the negative results could have been due to the fact that such skills are not being taught effectively. If future studies examine this approach, investigators should try to check whether participants acquired and practised the skills taught. However, an alternative possibility has to be considered - that despite the strong intuitive validity and popularity of the classic relapse prevention procedures, they do not produce the desired effect. Future studies may be better advised to focus on alternative approaches not studied extensively or at all so far, such as opportunistic use of nicotine replacement, contingency contracting, social support, cue exposure (only imaginary exposure has been studied so far), interventions aimed at maintaining abstainers' morale and awareness of the danger of feckless slips, and so forth.

Regarding pharmacological interventions, good large studies have investigated the extended use of bupropion and varenicline; however, NRT has been studied only in relatively small samples, as an add-on to bupropion trials and in paradigms likely to generate low treatment compliance, which lower the chance of detection of effects of the expected size. Given the good acceptability, safety, and cost profile of NRT, trials of extended NRT use in relapse prevention are needed.

Agreements and disagreements with other studies or reviews

One recent large review by Coleman and colleagues of relapse prevention interventions for abstinent smokers detected more positive results than ours for some outcomes (Agboola 2010; Coleman 2010). In particular, although we did not detect any significant effects in pooled comparisons, Coleman et al concluded that self-help materials, bupropion and nicotine replacement therapy were effective at six months and longer. We investigated the reasons for these discrepancies.

Coleman et al used similar search strategies and inclusion criteria to ours, hence our included studies lists map closely onto each other. Their review does not include some new studies added in the most recent update, nor does it include two studies from previous versions of this review (Juliano 2006 was excluded as it randomly assigned participants who had lapsed rather than abstainers; Klesges 2006 was excluded because participants included some never smokers). However, the differences in conclusions are not attributable to the exclusion of these studies. Differences between results for the most part are due to decisions about subgroups and outcomes presented.

Although our meta-analysis of bupropion includes an additional two studies (Killen 2006; Hays 2009) to the four presented by Coleman et al, the reason for the discrepancy in our pooled results from bupropion studies lies in the outcome data used. Coleman et al use different definitions of abstinence and different denominators; in particular, they did not always count dropouts as continuing smokers. We followed the standard methods used by the Cochrane Review Group, which resulted in a more conservative outcome. The difference in NRT results is attributable to subgroup decisions. Our pooled results suggested that NRT could be effective in unaided abstainers but did not detect an effect in assisted abstainers; Coleman et al merged the two groups and detected a significant effect overall. Finally, Coleman et al detected a significant effect of written self-help at long-term follow-up. The three included studies from their analysis are included in our analysis of behavioural interventions for unaided abstainers, and our analysis contains an additional two studies. However, the exclusion of these two studies did not change the overall effect in a sensitivity analysis; rather, the difference in results is largely due to the data presented for Brandon 2000. This was a factorial trial that tested access to a quitline and repeated mailings; whereas Coleman et al compared the arms that received mailings with the arms that did not (quitline only and control), we compared all intervention arms (quitline, quitline + mailings, mailings only) with the control arm and used slightly different data obtained via correspondence with the author.

With the exception of these three analyses, the results from Coleman et al are consistent with our own.

Authors' conclusions

Implications for practice

The available evidence does not support the use of any specific behavioural component or intervention to help smokers who have successfully quit for a short time to avoid relapsing to smoking again. The conclusion of lack of efficacy concerns specifically the traditional treatment focused on identifying and resolving tempting situations, as well as minimal interventions using one-off sessions and written materials. Hardly any evidence is available on alternative approaches. Until new positive evidence becomes available, it may be more efficient to focus resources on supporting initial cessation attempts rather than on providing extended relapse prevention interventions. Regarding pharmacotherapies, extended treatment with varenicline may prevent relapse. Extended treatment with bupropion is unlikely to have a clinically important effect.

Implications for research

The current research has limitations both in the methodology and in the treatment approaches tested. Future researchers, especially those exploring behavioural interventions, should take account of this in designing studies of adequate methodology and sample size, and in examining alternatives to attempts to teach skills to cope with risk situations. Studies of extended treatment with nicotine replacement are needed.

Acknowledgements

We would like to thank Sue Curry and Roger Secker-Walker for comments on earlier drafts of this review, as well as Esther Coren for consumer input. Hitomi Kobayashi assisted by translating a study in Japanese, Darius Razavi provided additional information on Mayer 2010 and Minxing Chen and David Wetter provided additional data on Wetter 2011.

Data and analyses

Download statistical data

Comparison 1. Behavioural interventions for abstinent pregnant/postpartum women
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Not smoking at delivery/ last follow-up prior to delivery81523Risk Ratio (M-H, Fixed, 95% CI)1.04 [0.98, 1.11]
1.1 Self-help intervention1171Risk Ratio (M-H, Fixed, 95% CI)1.05 [0.91, 1.21]
1.2 Individual counselling5641Risk Ratio (M-H, Fixed, 95% CI)1.01 [0.89, 1.15]
1.3 Telephone counselling2711Risk Ratio (M-H, Fixed, 95% CI)1.06 [0.99, 1.15]
2 Not smoking at longest follow-up after delivery123524Risk Ratio (M-H, Fixed, 95% CI)1.08 [0.99, 1.19]
2.1 Intervention during pregnancy5690Risk Ratio (M-H, Fixed, 95% CI)1.01 [0.82, 1.23]
2.2 Intervention initiated during pregnancy and continued post partum4989Risk Ratio (M-H, Fixed, 95% CI)1.12 [0.94, 1.33]
2.3 Intervention initiated after birth41845Risk Ratio (M-H, Fixed, 95% CI)1.10 [0.96, 1.25]
Analysis 1.1.

Comparison 1 Behavioural interventions for abstinent pregnant/postpartum women, Outcome 1 Not smoking at delivery/ last follow-up prior to delivery.

Analysis 1.2.

Comparison 1 Behavioural interventions for abstinent pregnant/postpartum women, Outcome 2 Not smoking at longest follow-up after delivery.

Comparison 2. Behavioural interventions for abstinent hospitalised smokers
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Cessation at longest follow-up3667Risk Ratio (M-H, Fixed, 95% CI)0.94 [0.78, 1.13]
Analysis 2.1.

Comparison 2 Behavioural interventions for abstinent hospitalised smokers, Outcome 1 Cessation at longest follow-up.

Comparison 3. Behavioural interventions for unaided abstainers
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Cessation at longest follow-up53561Risk Ratio (M-H, Fixed, 95% CI)1.08 [0.98, 1.19]
Analysis 3.1.

Comparison 3 Behavioural interventions for unaided abstainers, Outcome 1 Cessation at longest follow-up.

Comparison 4. Behavioural interventions for assisted abstainers
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Cessation at longest follow-up51462Risk Ratio (M-H, Fixed, 95% CI)1.00 [0.87, 1.15]
Analysis 4.1.

Comparison 4 Behavioural interventions for assisted abstainers, Outcome 1 Cessation at longest follow-up.

Comparison 5. Pharmacotherapy for unaided abstainers
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Cessation 12m after quit date22261Risk Ratio (M-H, Fixed, 95% CI)1.24 [1.04, 1.47]
1.1 Nicotine gum vs placebo after brief unassisted abstinence22261Risk Ratio (M-H, Fixed, 95% CI)1.24 [1.04, 1.47]
Analysis 5.1.

Comparison 5 Pharmacotherapy for unaided abstainers, Outcome 1 Cessation 12m after quit date.

Comparison 6. Pharmacotherapy for assisted abstainers
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Nicotine replacement therapy versus placebo. Cessation 12 m+ after quit date2553Risk Ratio (M-H, Fixed, 95% CI)1.04 [0.77, 1.40]
1.1 16 w nicotine gum vs. placebo1143Risk Ratio (M-H, Fixed, 95% CI)1.44 [0.77, 2.69]
1.2 16 w nicotine gum + bupropion vs. placebo gum + bupropion1146Risk Ratio (M-H, Fixed, 95% CI)0.96 [0.59, 1.56]
1.3 9 m nicotine inhaler vs. placebo1168Risk Ratio (M-H, Fixed, 95% CI)0.96 [0.54, 1.72]
1.4 9 m nicotine inhaler + bupropion vs. placebo inhaler + bupropion196Risk Ratio (M-H, Fixed, 95% CI)0.86 [0.39, 1.93]
2 Bupropion vs. placebo. Cessation 12 m+ after quit date61697Risk Ratio (M-H, Fixed, 95% CI)1.15 [0.98, 1.35]
2.1 52w bupropion vs placebo1110Risk Ratio (M-H, Fixed, 95% CI)0.96 [0.60, 1.55]
2.2 45w bupropion vs placebo1429Risk Ratio (M-H, Fixed, 95% CI)1.11 [0.82, 1.51]
2.3 24w bupropion vs placebo1176Risk Ratio (M-H, Fixed, 95% CI)1.46 [0.77, 2.77]
2.4 16w bupropion vs placebo1144Risk Ratio (M-H, Fixed, 95% CI)1.72 [0.95, 3.12]
2.5 16w bupropion + nicotine gum vs placebo + nicotine gum1145Risk Ratio (M-H, Fixed, 95% CI)1.14 [0.68, 1.92]
2.6 9m bupropion vs placebo1141Risk Ratio (M-H, Fixed, 95% CI)1.09 [0.64, 1.84]
2.7 9m bupropion + placebo inhaler vs double placebo197Risk Ratio (M-H, Fixed, 95% CI)0.82 [0.40, 1.68]
2.8 9m bupropion + nicotine inhaler vs placebo + nicotine inhaler193Risk Ratio (M-H, Fixed, 95% CI)1.01 [0.43, 2.39]
2.9 14w bupropion vs placebo1362Risk Ratio (M-H, Fixed, 95% CI)1.19 [0.84, 1.68]
3 Combination NRT & bupropion vs placebo. Cessation at longest follow-up2243Risk Ratio (M-H, Fixed, 95% CI)1.18 [0.75, 1.87]
4 Varenicline vs placebo. Cessation 12 m+ after quit date1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
5 Rimonabant vs placebo. Cessation 12 m+ after quit date1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
Analysis 6.1.

Comparison 6 Pharmacotherapy for assisted abstainers, Outcome 1 Nicotine replacement therapy versus placebo. Cessation 12 m+ after quit date.

Analysis 6.2.

Comparison 6 Pharmacotherapy for assisted abstainers, Outcome 2 Bupropion vs. placebo. Cessation 12 m+ after quit date.

Analysis 6.3.

Comparison 6 Pharmacotherapy for assisted abstainers, Outcome 3 Combination NRT & bupropion vs placebo. Cessation at longest follow-up.

Analysis 6.4.

Comparison 6 Pharmacotherapy for assisted abstainers, Outcome 4 Varenicline vs placebo. Cessation 12 m+ after quit date.

Analysis 6.5.

Comparison 6 Pharmacotherapy for assisted abstainers, Outcome 5 Rimonabant vs placebo. Cessation 12 m+ after quit date.

Comparison 7. Behavioural interventions for smokers. RP vs. cessation, matched for programme length
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Group or individual format therapy (+/- adjunct pharmacotherapy), cessation at longest follow-up10872Risk Ratio (M-H, Fixed, 95% CI)0.91 [0.73, 1.13]
2 Self-help format, cessation at longest follow-up191Risk Ratio (M-H, Fixed, 95% CI)1.52 [0.67, 3.46]
Analysis 7.1.

Comparison 7 Behavioural interventions for smokers. RP vs. cessation, matched for programme length, Outcome 1 Group or individual format therapy (+/- adjunct pharmacotherapy), cessation at longest follow-up.

Analysis 7.2.

Comparison 7 Behavioural interventions for smokers. RP vs. cessation, matched for programme length, Outcome 2 Self-help format, cessation at longest follow-up.

Comparison 8. Behavioural interventions for smokers. RP vs. cessation, different intensity programmes
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Cessation at longest follow-up7699Risk Ratio (M-H, Fixed, 95% CI)1.01 [0.80, 1.27]
1.1 More than four sessions for control group5546Risk Ratio (M-H, Fixed, 95% CI)0.93 [0.70, 1.23]
1.2 Four sessions or less for control group2153Risk Ratio (M-H, Fixed, 95% CI)1.23 [0.81, 1.86]
Analysis 8.1.

Comparison 8 Behavioural interventions for smokers. RP vs. cessation, different intensity programmes, Outcome 1 Cessation at longest follow-up.

Comparison 9. Interventions for smokers, tests of adjuncts to cessation programmes
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Behavioural interventions, cessation at longest follow-up5 Risk Ratio (M-H, Fixed, 95% CI)Subtotals only
1.1 Additional proactive telephone contact22527Risk Ratio (M-H, Fixed, 95% CI)1.06 [0.90, 1.23]
1.2 Additional web-based support1284Risk Ratio (M-H, Fixed, 95% CI)1.27 [0.70, 2.31]
1.3 Additional computer-delivered intervention1302Risk Ratio (M-H, Fixed, 95% CI)0.93 [0.64, 1.35]
1.4 Formulation of coping strategies11566Risk Ratio (M-H, Fixed, 95% CI)1.27 [0.97, 1.67]
2 Combined behavioural and pharma interventions, cessation at longest follow-up1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
2.1 Additional proactive telephone counselling + NRT1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
Analysis 9.1.

Comparison 9 Interventions for smokers, tests of adjuncts to cessation programmes, Outcome 1 Behavioural interventions, cessation at longest follow-up.

Analysis 9.2.

Comparison 9 Interventions for smokers, tests of adjuncts to cessation programmes, Outcome 2 Combined behavioural and pharma interventions, cessation at longest follow-up.

Appendices

Appendix 1. CRS search strategy

#1 relapse prevention:TI,AB,MH,EMT,XKY
#2 maintenance:TI,AB,MH,EMT,XKY
#3 (relapse NEAR prevent*):TI,AB,MH,EMT,XKY
#4 (relapse* NEAR smok*):TI,AB,MH,EMT,XKY
#5 recurrence:MH,XKY
#6 #1 OR #2 OR #3 OR #4 OR #5

What's new

Last assessed as up-to-date: 5 June 2013.

DateEventDescription
3 June 2013New citation required but conclusions have not changedNine new included studies have not changed pooled results or conclusions.
3 June 2013New search has been performedNew search run 2013; nine included studies added and risk of bias tables updated to current Cochrane tool.

History

Protocol first published: Issue 1, 2003
Review first published: Issue 1, 2005

DateEventDescription
22 October 2008New citation required and conclusions have changedIncludes evidence from one trial that extended treatment with varenicline reduces relapse
21 October 2008New search has been performedUpdated for issue 1, 2009 with 15 new included trials.
20 October 2008AmendedConverted to new review format.

Contributions of authors

PH, LFS and TL conceived of the review and developed the protocol. MJ performed previous work that informed the protocol. LFS designed and conducted the searches and screened the papers. PH, LFS and TL extracted data and agreed on study inclusion and grouping. PH and LFS conducted the analyses and jointly wrote the review. MJ and RW provided additional methodological, clinical and policy perspectives. JHB extracted data and contributed to the text and analyses for the 2013 update.

Declarations of interest

One author (PH) was involved in three of the studies included in the review.

Sources of support

Internal sources

  • University of Oxford, Department of Primary Health Care, UK.

  • National School for Health Research, School for Primary Care Research, UK.

  • Queen Mary's School of Medicine and Dentistry, UK.

External sources

  • NHS Research & Development Programme, UK.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Becona 1997

MethodsSetting: Cessation clinic, Spain
Recruitment: community volunteers
Group size: 36 to 40
Participants76 smokers, ≥ 10 cigs/day (excludes an untreated control group of 40, not randomly selected). 51% F, av age 34, av cigs/day 28
Interventions

Both conditions received 8 weekly sessions in groups of 36 to 40, duration NS, TQD week 4. 2 experienced therapists

1. Standard programme: motivational contract, nicotine fading, stimulus control

2. RP. As 1 + problem solving

OutcomesAbstinence at 12 m (definition NS)
Validation: CO < 8 ppm during therapy, informants during follow-up
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomization method not described
Allocation concealment (selection bias)Unclear riskNo information given
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot specified
Blinding of outcome assessment (detection bias)
All outcomes
Low riskBiochemically validated abstinence
Incomplete outcome data (attrition bias)
All outcomes
Low riskAll randomly assigned participants included in ITT analysis

Borland 2004

MethodsSetting: Quitline, Australia
Recruitment: volunteers calling a quitline to request S-H materials
Participants215 smokers who had quit at time of recruitment (other participants not included in this review)
Demographics for all participants: 54% F, approx 47% < 30 y, av cigs/day 21
63% had quit in previous week
Interventions

All participants received a quit pack at the time of first contact with the quitline, 1 to 2 days before recruitment

1. Series of tailored advice letters based on standardised telephone assessment. 2 to 3 pages, tailored in part by stage of change, timing varied

2. No further intervention

OutcomesAbstinence at 12 m, sustained for 6 m
Validation: none
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskComputer-generated numbers with even numbers allocated to intervention
Allocation concealment (selection bias)Low riskID number generated after agreement to participate
Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding not possible because of nature of the intervention, but "participants in each condition [did] not know about the other condition unless they specifically asked ... (none did)"
Blinding of outcome assessment (detection bias)
All outcomes
Low riskNo blinding or validation of smoking status, but because of low-contact nature of intervention, differential misreport of smoking unlikely
Incomplete outcome data (attrition bias)
All outcomes
Low riskLosses to follow-up 23% in each group; all included in ITT analysis

Brandon 1987

MethodsSetting: Cessation clinic, USA
Recruitment: community volunteers
Participants39 abstainers at the end of cessation treatment
Sex NS, av age 31, av cigs/day 27
Treatment: groups of 3 to 7 (probably)
Therapists: 3, counterbalanced across treatments
Interventions

All-included cessation programme 6 × 2 h over 2 w

1. RP 4 × 1.5 h sessions, 2, 4, 8, 12 w post-cessation: self-monitoring, advice, assignment of exposure and coping exercises

2. No maintenance, one assessment session at 12 w

OutcomesAbstinence at 12 m (assume PP) (phone assessment, non-therapist).
Validation: CO only during treatment, phoning 2 collaterals-no results given
NotesA treatment arm that included rapid puffing not included
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomly by treatment group before cessation programme, method not described
Allocation concealment (selection bias)Unclear riskNo information given
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot specified
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskBiochemically validated abstinence but no results provided
Incomplete outcome data (attrition bias)
All outcomes
Unclear risk8 randomly assigned participants did not achieve initial cessation and are not included in analysis as their allocation is not given

Brandon 2000

MethodsSetting: Community, USA
Recruitment: advertisements for ex-smokers wanting to avoid relapse
Participants584 ex-smokers (abstinent > 7 days at baseline).
Av age 49, median abstinence 6.5 m, mean 16 m
Interventions2 × 2 factorial design testing mail and phone intervention
Mailings condition: 8 Stay Quit booklets mailed at 1, 2, 3, 5, 7, 9, 12 m
Hotline condition: information about Stay Quit hotline. Asked to call to register. Participants were called if they did not register within 2 w and at 3 m if they had not called
Minimal contact condition received; first Stay Quit booklet.
OutcomesAbstinence at 12 m (no smoking in past 7 days)
All participants were abstinent at baseline, and relapse rates were low.
Validation: CO < 10 ppm for participants living within 75 miles of laboratory
NotesNo true control
Of 804 randomly assigned, results were based on 584 who met inclusion criteria and were sent materials. (Until 2009 update, denominator of 446 was used. Author provided additional data)
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomization method not described
Allocation concealment (selection bias)Unclear riskNo details given
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot specified
Blinding of outcome assessment (detection bias)
All outcomes
Low risk"The CO results from the subsample suggest that participants' self-reported smoking status had satisfactory validity"
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSome post randomization dropouts not included but equally distributed

Brandon 2004

MethodsSetting: Community, USA
Recruitment: advertisements for ex-smokers wanting to avoid relapse
Participants481 ex-smokers (abstinent > 7 days at baseline)
66% F, av. age 52, av cigs/day 25. Median 75 days of abstinence
Interventions

2 × 2 factorial design testing effects of contact versus content

1. Repeated mailings. High contact-high content. 8 "Forever Free" booklet mailings at enrolment and 1, 2, 3, 5, 7, 8, 12 m

2. Massed mailings. Low contact-high content. Same 8 booklets at enrolment

3. Repeated letters. High contact-low content. Single "Forever Free" booklet, 7 supportive letters, same schedule as 1. Provided extended contact and social support without skills training

4. Control. Low contact-low content. Single booklet, no further contact

OutcomesAbstinence at 24 m (no smoking in past 7 days)
Validation: CO for 21 local quitters, no misreporting identified
NotesNew for 2009 update
No true control. Other 3 arms compared with single booklet condition in main analysis. Of 895 randomly assigned, results based on 431 who met inclusion criteria and returned follow-up questionnaire. Non-responders excluded rather than assumed to have relapsed
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomization method not described
Allocation concealment (selection bias)Unclear riskNo details given
Blinding of participants and personnel (performance bias)
All outcomes
Low riskBecause of the nature of the intervention, blinding not possible, but no additional phone or face contact between personnel and participants; lack of blinding unlikely to affect performance
Blinding of outcome assessment (detection bias)
All outcomes
Low riskMinimal contact, misreport unlikely to be differential and validation of subgroup did not identify any misreporting
Incomplete outcome data (attrition bias)
All outcomes
Low risk85% reached at 24 m, no differential dropout

Buchkremer 1991 1

MethodsSetting: Cessation clinic, Germany
Recruitment: community volunteers
Participants256 smokers, no demographic details
Interventions

5 conditions, partly factorial. All received nicotine patch, dose individualised for conditions 1 to 4, +9 weekly sessions, incl reduction, self-monitoring, contract management, risk avoidance. TQD after 6 w

1. Additional training in relapse-coping strategies (during cessation phase)

2. Additional 3 booster sessions, 6 m after end of main therapy

3. Relapse-coping and boosters

4. Control

5. Control (fixed-dose nicotine patch)

OutcomesAbstinence 12 m post-EOT (PP). Rates estimated from graphs
Validation: random urine nicotine, 'almost 100% conformity', no correction
Notes3 versus 4 in contact matched comparison, 1 + 2 versus 4 in extended contact comparison
Inclusion of control group 5 (fixed dose) would marginally increase intervention benefit
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear risk"Randomly assigned to experimental groups after previously being matched for age, sex and cigarette consumption"
Allocation concealment (selection bias)Unclear riskNo details given
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNo information provided
Blinding of outcome assessment (detection bias)
All outcomes
Low riskNo blinding reported but biochemical confirmation taken at random, with 'almost 100% conformity'
Incomplete outcome data (attrition bias)
All outcomes
Unclear risk15/256 (5.9%) dropouts excluded, assignment not given, so not included in analysis

Buchkremer 1991 2

MethodsSetting: Cessation clinic, Germany
Recruitment: community volunteers
Participants185 smokers, no demographic details
Interventions

4 conditions, partly factorial. All received nicotine patch (dose individualised for conditions 1 to 3) + 9 weekly sessions, incl reduction, self-monitoring, contract management, risk avoidance. TQD after 6 w

1. Relapse coping training using role play, TQD at 6 w

2. Modified relapse coping. Rapid abstinence, TQD session 4, covert sensitisation, thought-stopping

3. Control, individualised patch dose

4. Control, fixed patch dose

OutcomesAbstinence 12 m post-EOT (PP). Rates estimated from graphs
Validation: random urine, 'almost 100% conformity', no correction
Notes1 + 2 versus 3 in contact matched comparison. Inclusion of control group 4 (fixed dose) would marginally increase intervention benefit
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear risk'Randomly assigned to experimental groups after previously being matched for age, sex and cigarette consumption'
Allocation concealment (selection bias)Unclear riskNo details given
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNo information provided
Blinding of outcome assessment (detection bias)
All outcomes
Low riskNo blinding reported but biochemical confirmation taken at random, with 'almost 100% conformity'
Incomplete outcome data (attrition bias)
All outcomes
Unclear risk23/185 (12.4%) dropouts excluded, assignment not given, so not included in analysis

Conway 2004

MethodsSetting: Naval training, USA
Recruitment: smokers who had enforced abstinence during naval training, unselected, not volunteers
Participants1682 female navy recruits with a history of smoking (661 reached at follow-up). All should have been abstinent for 2 m during training
av age 19, no details of cigs/day
Interventions

1. 6 mail contacts over 12 m, at 1, 2, 4, 5, 7, 10 m (2 after follow-up), 1-page flyers, cognitive-behavioural RP; stress management, weight, fitness, tailored for naval women

2. Access to toll-free telephone helpline for support and counselling on RP and quitting if relapse occurred, cognitive-behavioural approach. Once participant called, sessions scheduled in line with risk of relapse

3. No intervention control

OutcomesAbstinence at 12 m (30 day) (Edwards 1999 reports 6 m outcomes)
Validation: none
NotesResults not displayed graphically because denominators not explicit. No evidence of intervention effect. Impact of clustering was negligible
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskCluster randomization by division (80 people)
Allocation concealment (selection bias)Unclear riskNo details given
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNo information provided
Blinding of outcome assessment (detection bias)
All outcomes
Low riskSelf-reported smoking status, interventions of varying intensities, but no face-to-face contact, so judged to be unlikely
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskHigh loss to follow-up (52% at 12 m); participants lost to follow-up not broken down by group; unclear whether included in final denominators

Covey 2007

MethodsSetting: Cessation clinic, USA
Recruitment: community volunteers quit after 8 w bupropion & nicotine patch
Participants289 abstainers (excludes 5 withdrawing consent before starting meds)
45% F, av age 43, av cigs/day 21
Therapists: counsellors, 1 m training
Interventions

All participants received 8 w open-label bupropion and nicotine patch (21 mg with weaning) for 7 w from TQD. Transition procedures preserved blinding for RP phase but allowed weaning from bupropion. Individual counselling, including CBT techniques, 15 min × 6 during open-label, ×4 during RP, ×2 during follow-up

1. Bupropion (300 mg) and nicotine gum (2 mg, use as needed to manage craving) for 16 w

2. Bupropion and placebo gum

3. Nicotine gum and placebo pill (150 mg bupropion for first week)

4. Double placebo (150 mg bupropion for first week)

OutcomesAbstinence (no relapse to 7 days of smoking) for 12 m (10 m after randomization, 6 m after EOT) (Primary outcome for study was time to relapse)
Validation: CO ≤ 8ppm at each visit
NotesNew for 2009 update
Contributes to NRT, bupropion and combination therapy analyses
Quit rate after open-label treatment was 52%, so the final quit rate of 30% for combination therapy is equivalent to ˜16% of people starting treatment
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk"A statistician who did not participate in the clinical phases of the study provided computer-generated randomization lists that were not accessible to the clinical staff", stratified by gender and depression history
Allocation concealment (selection bias)Low riskA research nurse who did not have direct contact with participants prepared individual medication kits based on the randomization schedule
Blinding of participants and personnel (performance bias)
All outcomes
Low risk"Participants and clinical researchers with direct participant contact were blinded to the randomization". Identical placebos used
Blinding of outcome assessment (detection bias)
All outcomes
Low riskBiochemical validation used at each visit
Incomplete outcome data (attrition bias)
All outcomes
Low risk5 randomly assigned participants withdrew before double-blind phase. Greater loss to follow-up in double placebo, losses included in ITT analysis

Croghan 2007

MethodsSetting: Clinic, USA
Recruitment: community volunteers for pharmacotherapy cessation and RP trial
Participants405 abstainers after 3 m pharmacotherapy, 74 from inhaler, 141 bupropion, 190 combination
Participant characteristics not presented at start of RP phase
InterventionsIn cessation phase, participants had been randomly assigned to bupropion (300 mg), nicotine inhaler (up to 16 cartridges/day) or combination. Physician advice at entry, brief (<10 min) counselling at monthly study visits (total 12 to 18, including RP phase) and S-H. Abstainers (7 day PP after 3 m therapy) eligible for RP phase
RP intervention randomly assigned single-therapy abstainers to continue cessation therapy or placebo for 9 m
Combined therapy abstainers randomly assigned to 4 groups: combination, placebo and single therapy, or double placebo
OutcomesAbstinence at 15 m (from TQD, 12 m from RP start, 3 m from EOT) (PP)
Validation: CO ≤ 8ppm
NotesNew for 2009 update
Arms contribute to NRT, bupropion and combination therapy analyses, ignoring differences in cessation induction therapy
Cessation rates at end of induction phase were 14% for inhaler, 26% for bupropion and 34% for combination
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandomization using a dynamic allocation procedure and balancing stratification factors
Allocation concealment (selection bias)Low riskRandomization procedure makes prior knowledge of allocation unlikely
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskPlacebo used, but insufficient information provided re: blinding to permit judgement
Blinding of outcome assessment (detection bias)
All outcomes
Low riskBiochemical validation used
Incomplete outcome data (attrition bias)
All outcomes
Low riskLosses to follow up post-medication were high and were not enumerated by group, but all were included in ITT analysis

Curry 1988

MethodsSetting: Cessation clinic, USA
Recruitment: community volunteers
Participants139 smokers, 48 in group arms, 91 in S-H arms
Therapists for groups: 2 teams of 2 PhD psychologists. Each team led one group in each programme
Interventions

Compared 2 approaches, in both group and S-H formats

Groups met 8 × 2 h weekly, incl relaxation training, enlisting social support and practising alternative behaviours. S-H intervention provided same components in 8 workbooks

1. RP: focused on smoking as learned behaviour. Quit day (for group format) at 3rd session. Additional elements included identifying high-risk situations, cognitive restructuring and role playing

2. 'Absolute Abstinence' (AA) group. Focused on addictive component of smoking. Quit day (for group format) at 5th session. Additional elements included focused smoking, health education and contingency contract

OutcomesAbstinence from m 9 to m 12 of follow-up
Validation: saliva thiocyanate and two collateral verifiers
NotesGroup and S-H arms used in different comparisons within the matched contact time section
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskPart by coin toss and part random number table. Friends co-randomly assigned to same programme but not necessarily same format. More assigned to S-H than group by design
Allocation concealment (selection bias)High riskNo details given, but randomization procedure makes it likely that it was not concealed
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNo information reported
Blinding of outcome assessment (detection bias)
All outcomes
Low riskAbstinence validated
Incomplete outcome data (attrition bias)
All outcomes
Low riskOnly 69% began treatment. Losses to follow-up included an ITT analysis

Davis 1986

MethodsSetting: Cessation clinic, USA
Recruitment: community volunteers
Group size 3 to 8
Participants45 smokers who completed treatment
Therapists: 9 advanced clinical psychology graduate students with no previous experience. Each conducted one group
Interventions

All conditions received 6 × 1½ to 2 h weekly meetings based on Pomerleau and Pomerleau broad-spectrum cessation package. TQD w 5

1. 'Experimental' condition added active cognitive behavioral skills training focusing on 11 problem situations

2. 'Enhanced control' added discussion of same problems

3. 'Control' using Pomerleau and Pomerleau alone

OutcomesAbstinence at 12 m (PP)
Validation: CO
Notes1 and 2 treated as RP
Condition 2 not displayed. 3/14 quit
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomization method not described
Allocation concealment (selection bias)Unclear riskNo details given
Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding not possible because of nature of the intervention, but all participants received same amount of contact, and no therapists had previous experience with stop-smoking groups, hence performance bias unlikely
Blinding of outcome assessment (detection bias)
All outcomes
Low riskBiochemical validation used
Incomplete outcome data (attrition bias)
All outcomes
Unclear risk5 pretreatment and 6 dropouts during treatment excluded, assignment not specified

Emmons 1988

MethodsSetting: Cessation clinic, USA
Recruitment: community volunteers
Participants49 smokers; 71% F, av age 41, av cigs/day 31 (significant difference between groups, 35 vs 27)
Interventions

1. Cessation programme with RP focus. 8 × 1½ h weekly, TQD between 3 and 4. pre-quit self-monitoring. Choice of 'cold turkey' or gradual reduction. Relaxation, role-play, cognitive coping

2. Broad-spectrum (BS) programme. 12 × 1 h over 8 w. TQD between 3 and 4. Included nicotine fading

OutcomesAbstinence at 6 m (PP) (EOT and 3 m also reported)
Validation: saliva thiocyanate ≤ 85 microg/ml
NotesIncluded in contact matched section, although different number of sessions
Inclusion of 4 non-completers would increase apparent benefit of BS
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomization in blocks, method not described
Allocation concealment (selection bias)Unclear riskNo details given. Friends and relatives assigned to same condition, and significant baseline differences between groups; BS smoked more
Blinding of participants and personnel (performance bias)
All outcomes
Low risk"Although facilitators knew that different treatments were being conducted, they were unaware of the components of the alternate treatments". Same duration of contact in both groups. Performance bias unlikely
Blinding of outcome assessment (detection bias)
All outcomes
Low riskBiochemically validated outcome
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskResults exclude 4 pretreatment dropouts, 4 non-completers (3RP, 1BS), 1 medical problem

Ershoff 1995

MethodsSetting: HMO health centre, USA
Recruitment: pregnant women who had quit smoking since becoming pregnant
Participants171 pregnant recent quitters, av length of prior abstinence 31 days, 58% had >7 days of total abstinence
Av age 25, av cigs/day 10
Interventions

1. RP. S-H booklets; 4 on cessation given at baseline visit, 4 RP-oriented mailed at weekly intervals

2. Control. 1-page tip sheet on behavioural techniques for avoiding relapse

Both groups had a 2 min discussion on smoking & pregnancy with health educator, were given 2-page pamphlet, congratulated on quitting

OutcomesPP (7 day), late in 3rd trimester (also w 26 and w 34 of pregnancy)
Validation: cotinine, at least 1 ≤ 10 ng/mL and none ≥ 80 ng/mL
Notes11% of women misreported abstinence
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomization method not described
Allocation concealment (selection bias)Low riskAllocation before participant contact, blind until end of baseline data collection
Blinding of participants and personnel (performance bias)
All outcomes
Low risk"The health educator was blind to group assignment until the end of data collection... The program was presented as a standard part of prenatal care... Patients had no further contact with the prenatal intake health educator. Prenatal care providers were blind to group assignment, and no effort was made to modify their usual counselling practices"
Blinding of outcome assessment (detection bias)
All outcomes
Low riskBiochemically validated
Incomplete outcome data (attrition bias)
All outcomes
Low risk37 (22%) exclusions due to abortion, miscarriage, move from HMO

Fortmann 1995

MethodsSetting: Community, USA
Recruitment: smokers identified via a random telephone survey (volunteers)
Participants1044 smokers able to quit for 24 h; 42% F, av age 40, av cigs/day 20
Interventions

Factorial trial of nicotine gum and S-H for RP. All participants also offered an incentive of $100 for quitting for 6 m

1. Nicotine gum 2 mg

2. S-H materials

3. Nicotine gum and S-H materials

4. Monetary incentive only

OutcomesPP abstinence at 12 m
Validation: CO < 9 ppm, salivary cotinine < 20 ng/mL
Notes1 and 3 compared with 2 and 4 to assess effect of nicotine gum
2 and 3 compared with 1 and 4 to assess effect of behavioural component
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomization method not described
Allocation concealment (selection bias)Unclear riskNo details given
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNo details given
Blinding of outcome assessment (detection bias)
All outcomes
Low riskBiochemical validation
Incomplete outcome data (attrition bias)
All outcomes
Low risk94% followed up at 12 m, all participants included in ITT analysis

Hajek 2001

MethodsSetting: Antenatal clinics, UK
Recruitment: pregnant smokers and recent quitters
Participants249 pregnant recent (within 6 m) quitters, average abstinence 7 w (smokers also in trial, not included for this review)
Av age 28, av cigs/day approx 12
Interventions1. Advice from midwife with explanation of CO reading, pamphlet, prompt placed in notes for reinforcement
2. Usual midwife care
OutcomesAbstinence at 12 m (prolonged for last 12 w of pregnancy and 6 m since birth), also at birth
Validation: CO ≤ 10ppm
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskCluster randomized by midwife. "The allocation schedule was generated by drawing of folded tags with Intervention or control designations and assigning them to consecutive names on the list of midwives"
Allocation concealment (selection bias)High riskRandomized midwives were responsible for recruiting participants, fewer control midwives recruited any, so possible recruitment bias
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot reported
Blinding of outcome assessment (detection bias)
All outcomes
Low riskBiochemically validated
Incomplete outcome data (attrition bias)
All outcomes
Low riskWomen who were untraceable or unsuitable for follow-up were excluded, other losses included as smokers

Hajek 2002

MethodsSetting: 17 hospitals, UK
Recruitment: inpatients with MI or for CABG
Participants540 smokers or recent quitters (26%) who had not smoked since admission to hospital and motivated to quit
Interventions1. As control + CO reading, booklet on smoking and cardiac recovery, written quiz, offer to find support 'buddy', commitment, reminder in notes. Implemented by cardiac nurses during routine work, est time 20 m
2. Verbal advice, 'Smoking and Your Heart' booklet
OutcomesAbstinence at 12 m, sustained (no more than 5 cigs since enrolment and 7 day PP)
Validation: saliva cotinine < 20 ng/mL (CO used at 6 w follow-up and for visits at 12 m)
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomization method not described
Allocation concealment (selection bias)Low riskNurses opened a "serially numbered, opaque, sealed envelope designating the patient's allocation"
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot reported, some contamination possible
Blinding of outcome assessment (detection bias)
All outcomes
Low riskBiochemical validation used
Incomplete outcome data (attrition bias)
All outcomes
Low risk26 deaths and 9 moved. address excluded from denominator in analysis; all others lost to follow-up counted as smokers

Hall 1984

MethodsSetting: Clinic, USA
Recruitment: media adverts and referral
Participants135 smokers; 59% F, av age approx 36, av cigs/day 29
Therapists: 2 psychologists, randomly assigned to groups
Interventions2 × 2 factorial trial, aversive smoking conditions collapsed
1. Skills training, 14 × 75 min sessions. 8 sessions over 3 w involved 6 s or 30 s aversive smoking. 6 sessions over w 1 to 6 covered relaxation, commitment and cost benefits, and RP skills with role-play of risk situations
2. Discussion control. Same aversive smoking. Other 6 sessions used self-scoring tests and group discussion. Discussion of specific skills discouraged
OutcomesAbstinence at 12 m (PP)
Validation: CO < 10 ppm, plasma thiocyanate < 85 ng/mg and confirmation from significant other
NotesMatched for contact time
Author tested for therapist and cohort main effects. None significant
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomization method not described
Allocation concealment (selection bias)Unclear riskNo details given
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNo details given
Blinding of outcome assessment (detection bias)
All outcomes
Low riskBiochemical validation used
Incomplete outcome data (attrition bias)
All outcomes
Low risk8 dropouts from grp 1 and 4 from grp 2 before start of RP sessions reincluded in this analysis

Hall 1985

MethodsSetting: Clinic, USA
Recruitment: referred by physicians, friends or self
Participants84 smokers in relevant arms; 53% M, av age 38, av cigs/day 30.5
Therapists: 2 psychologists
Interventions1. Intensive behavioural treatment (incl RP skill training, relaxation, 30 s aversive smoking of 3 cigs). 14 × 75 min sessions over 8 w
2. Same as 1. + 2 mg nicotine gum available for 6 m
3. Low-contact + nicotine gum. Met 4 × in 3 w, educational materials, written exercises, group discussion
OutcomesAbstinence at 52 w (assume PP)
Validation: CO < 10 ppm, thiocyanate < 85 mg/mL, reports of significant others (biochemical measures failed to confirm self-report in 3 instances)
Notes2 versus 3, not matched for contact time, controlled for gum. 1 not included in meta-analysis; 10/36 quit
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomly assigned within time constraints, method not described
Allocation concealment (selection bias)Unclear riskNo details given
Blinding of participants and personnel (performance bias)
All outcomes
High riskNo placebo NRT; no blinding.
Blinding of outcome assessment (detection bias)
All outcomes
Low riskBiochemical validation used
Incomplete outcome data (attrition bias)
All outcomes
Low risk3 dropouts in conditions 1 and 2 are assumed to be included in denominator for reported % abstinent used to derive numbers quit

Hall 1987

MethodsSetting: Clinic, USA
Recruitment: community volunteers or referrals
Participants139 smokers; 53% M, av age 39, av cigs/day 30
Therapists: advanced graduates in clinical psychology or health psychology
Interventions2 × 2 factorial trial. Nicotine gum/placebo arms collapsed
1. Intensive behavioural treatment incl 6 s aversive smoking, RP skills training, written exercises. 14 × 75 min sessions (period not stated)
2. 'Low contact', incl written exercises, educational materials, group discussions, quitting techniques. 5 × 60 min
OutcomesAbstinence at 52 w (assume PP)
Validation: thiocyanate < 95 mm/L (unless marijuana use reported), CO < 8 ppm, significant other
NotesNot matched for contact time
No reported interaction between behaviour therapy condition and gum condition so gum/no gum collapsed
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomization method not described
Allocation concealment (selection bias)Unclear riskNo details given
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskPlacebo gum used but gum/no-gum conditions collapsed in meta-analysis. No information provided re behavioural sessions in this domain
Blinding of outcome assessment (detection bias)
All outcomes
Low riskBiochemical validation used
Incomplete outcome data (attrition bias)
All outcomes
Low risk6 dropouts in 1 and 5 in 2 included in ITT analyses. "Differences between conditions were not statistically significant"

Hannöver 2009

MethodsSetting: Maternity services, Germany
Recruitment: postpartum women in maternity wards
Participants304 women who had not smoked for 4 w at baseline assessment
Interventions1. Counselling using motivational interviewing. Face-to-face session ˜40 days postpartum, telephone boosters 4 & 12 w later
2. Usual care from health system, S-H materials on postpartum smoking and partner smoking
OutcomesSustained abstinence since birth of baby at 24 m (at 6 m, 12 m, PP also reported)
Validation: none
NotesBaseline assessment was conducted a median of 35 days after birth
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)High riskAlternation of screening forms
Allocation concealment (selection bias)High riskAlternate allocation done at study centre so not known to screener in advance, reducing likelihood of selection bias
Blinding of participants and personnel (performance bias)
All outcomes
Unclear risk"The nature of the intervention made blinding impossible", but assessors "were blind to the women's group membership"
Blinding of outcome assessment (detection bias)
All outcomes
High riskSelf-reported cessation only, intervention face-to-face and intensive compared with control, differential misreport possible
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskParticipants who revoked participation before baseline assessment are not included in denominators

Hasuo 2004

MethodsSetting: Hospital, Japan
Recruitment: Hospitalised volunteers, recently quit or expecting to quit in hospital.
Participants106 smokers, quit on day of hospital discharge 87% M, av age 60. 83% quit before admission
Interventions1. In-hospital counselling from public health nurse, 3 × 20 min sessions, + 3 × 5 min calls, 7, 21, 42 days postdischarge
2. Control: in-hospital counselling only
OutcomesAbstinence at 12 m (assume PP)
Validation: Urine cotinine
NotesNew for 2009 update
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandomization by computer stratified by smoking status, FTND and self-efficacy
Allocation concealment (selection bias)Low riskTherapists notified of assignment after allocation
Blinding of participants and personnel (performance bias)
All outcomes
Low riskPublic health nurse and participant did not know allocation until the day before discharge, so common treatment component unlikely to be affected by performance bias
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot clear whether results are self-report or cotinine-validated
Incomplete outcome data (attrition bias)
All outcomes
Low risk106 excludes 6 deaths within 12 m and 8 who were smoking on day of discharge, includes all other losses

Hays 2001

MethodsSetting: Clinics, USA, 5 sites
Recruitment: 784 community volunteers for cessation and RP trial
Participants429 abstainers (previously ≥ 15 cigs/day) quit after 7 w open-label bupropion; 51% F, av age 46, av cigs/day 26
InterventionsAll participants first received 7 w bupropion, physician advice, S-H materials and brief individual counselling at follow-up visits to assist cessation
1. Bupropion 300 mg/day, 45 w
2. Placebo
OutcomesContinuous abstinence at 2y (1 y after EOT)
Validation: CO ≤ 10 ppm
NotesQuit rate after open-label phase was 59%, so the final quit rate of 29% in the bupropion group is equivalent to 17% of people starting treatment
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk"Randomization to the placebo or bupropion groups was computer generated at a central location..."
Allocation concealment (selection bias)Low riskCode held centrally, investigators blind
Blinding of participants and personnel (performance bias)
All outcomes
Low risk"...the investigators did not know the patient assignments. All bupropion and placebo pills were identical in shape, size, and color"
Blinding of outcome assessment (detection bias)
All outcomes
Low riskBlinding reported, and abstinence biochemically validated
Incomplete outcome data (attrition bias)
All outcomes
Low risk74% completed study, 2 deaths excluded, all other withdrawals included in ITT analysis

Hays 2009

Methods

Setting: Clinic, USA

Recruitment: 195 community volunteers for cessation and RP trial (110 included in RP trial)

Participants

110 recovering alcoholic abstainers with at least 1 y continuous abstinence from alcohol and drugs, 18+ years old, smoking at least 20 cpd for previous year. Quit for at least last week of 8 w patch therapy

78% M; av age 44; av cpd 29.9 (in initial population of 195 volunteers)

Interventions

All participants first received brief weekly counselling sessions and nicotine patch for 8 w. Patch tailored on the basis of baseline serum cotinine concentration

1. Bupropion: 150 mg/day first 3 d, then 300 mg/d until w 52

2. Placebo on same schedule

Brief individual counselling (≤ 10 min) at each clinic visit (weekly for w 9-12, monthly for w 13-24, then at 52, 53, 64 and 76 w)

Outcomes

Abstinence at 76 w (continuous and 7 d PP)

Validation: CO < 8 ppm

Notes

New for 2013 update

Study does not report number of participants allocated to each group or number of successful abstainers in each group; numbers obtained through extrapolation

Authors contacted to clarify re discrepancy in 76 w data, but no response

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear risk"Randomized", method not stated
Allocation concealment (selection bias)Unclear riskMethod not described
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskDescribed as "double-blind", placebo used, but no further information given
Blinding of outcome assessment (detection bias)
All outcomes
Low riskSmoking status biochemically validated
Incomplete outcome data (attrition bias)
All outcomes
Low riskAt w 76, similar rate of dropout in both groups (34% intervention; 37% control). Participants lost to follow-up counted as relapsed smokers
Other biasUnclear riskDiscrepancy in data: at 76 w, 7 d PP less than continuous abstinence

Hurt 2003

MethodsSetting: Clinics, USA, 14 sites
Recruitment: 578 community volunteers for cessation and RP trial
Participants176 abstainers (previously ≥ 15 cigs/day) quit after 8 w of nicotine patch; baseline group: 57% F, av age 42, av cigs/day 26
InterventionsAll participants first received nicotine patch for 8 w at a dose of 22, 33 or 44 mg/day, matched to baseline cigs/day. Brief advice to quit and S-H materials but no formal counselling
1. Bupropion 300 mg/day for 6 m
2. Placebo
No additional counselling during maintenance phase
OutcomesAbstinence at 12 m (PP) (6 m after EOT).
Validation: CO < 8 ppm
NotesQuit rate after open-label phase was 31%, so the final quit rate of 22% in the bupropion group is equivalent to 7% of people starting treatment
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomized by 'dynamic allocation', stratified on sex, cigs/day and years of smoking
Allocation concealment (selection bias)Unclear riskNot explicit, although randomization procedure makes concealment probable
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskDescribed as "double-blind", placebo used, but no further information given
Blinding of outcome assessment (detection bias)
All outcomes
Low riskBiochemical validation used
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskAll participants lost to follow-up counted as smokers, but numbers not provided

Japuntich 2006

MethodsSetting: Clinic/internet, USA
Recruitment: community volunteers
Participants284 smokers (≥ 10 cigs/day); 55% F, av age 41, av cigs/day 22
InterventionsAll participants received bupropion (300 mg) for 9 w, 3 brief (20 min) individual counselling sessions, 5 clinic visits for assessment, monthly assessment calls
1. Access to Comprehensive Health Enhancement Support System for Smoking Cessation and Relapse Prevention (CHESS SCRP) for 12 w, computer and access provided, daily use recommended, reminders to log on up to 3 times a week
2. No additional support
OutcomesAbstinence at 6 m (PP)
Validation: CO ≤ 10ppm
NotesNew for 2009 update
12 m follow-up results not published
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomization method not described
Allocation concealment (selection bias)Unclear riskNo details given
Blinding of participants and personnel (performance bias)
All outcomes
Low riskNo details given, but as support provided to both groups pre-intervention, and not during intervention period, performance bias unlikely
Blinding of outcome assessment (detection bias)
All outcomes
Low riskBiochemical validation used
Incomplete outcome data (attrition bias)
All outcomes
Low risk20% losses to follow-up and intervention participants who didn't get computer included in ITT analysis

Joseph 2011

Methods

Setting: Minnesota, USA

Recruitment: community volunteers (via local labor unions)

Participants

443 adult smokers of at least 5 cpd interested in quitting in next 14 d

60.2% F, av age 42, av cpd 17.7

Interventions

All participants received 5 telephone calls and NRT (patch; gum; lozenge, provision modelled on common clinical practice) by mail for 4 w. Randomly assigned to:

1. Longitudinal care modelled on chronic disease mgmt approach. Telephone counselling and NRT by mail for additional 48 w. Counsellors aimed to call every 2 w but adjustment based on participants’ progress/receptivity; if participants chose not to make a quit attempt or reduce, calls made monthly

2. Usual care. 1 additional call at 8 w

Outcomes

6 m prolonged abstinence at 18 m follow-up

Validation: none

Notes

New for 2013 update

Number abstinent not provided, extrapolated from percentages given

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk"Participants were randomly assigned... by a computer-generated scheme, blocked in masked groups of 20"
Allocation concealment (selection bias)Low risk"The randomization schedule was maintained by personnel independent from the study"
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot specified, allocation occurred before end of common treatment component
Blinding of outcome assessment (detection bias)
All outcomes
Low riskSelf-reported outcome only, but no face-to-face contact, hence differential misreport judged unlikely
Incomplete outcome data (attrition bias)
All outcomes
Low riskLow and similar rates of loss to follow-up in both groups (8.6% intervention, 8.1% control); dropouts counted as smokers in ITT analysis

Juliano 2006

MethodsSetting: Clinic, USA
Recruitment: community volunteers
Participants34 early lapsers (within 14 days) out of 67 smokers (≥15 cigs/day) enrolling in cessation phase; initial sample 61% F, av age 40
InterventionsMost participants received bupropion, all received counselling (before quitting, 30 min on quit day) and S-H materials. Participants reported smoking status daily. Lapsers were randomly assigned:
1. Rapid smoking. Puff every 6 s, 6 trials of up to 3 cigs, 5 min break between. Counselling in 30 to 45 min break between 3rd and 4th trials. Intention to provide 3 sessions, preferably on consecutive days, as soon as possible after lapse
2. Usual care-structured interview about lapse via telephone
OutcomesAbstinence at 6 m (PP)
Validation: CO ≤ 6 ppm
NotesNew for 2009 update. Included in behavioural interventions for assisted abstainers but not pooled; both conditions had RP content. 16/20 attended a rapid smoking session, 11 completed 3 sessions
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomization method not described
Allocation concealment (selection bias)Unclear riskNo details given
Blinding of participants and personnel (performance bias)
All outcomes
High riskNo blinding, control participants aware of intervention provided
Blinding of outcome assessment (detection bias)
All outcomes
Low riskBiochemical validation used
Incomplete outcome data (attrition bias)
All outcomes
Low riskAll losses to follow-up included in ITT analysis

Killen 1984

MethodsSetting: Clinic, USA
Recruitment: community volunteers
Participants64 smokers (44 in relevant arms); 72% F, av age 44, av cigs/day 32
Behaviour therapy provided by 2 psychologists, 1 medical social worker, assigned randomly to treatment conditions, group size 10 to 12
InterventionsAll participated in cessation training (incl cognitive-behavioural skills training and an aversive smoke-holding procedure), 4 × 1½ h sessions over 4 days, in groups of 10 to 12
1. Nicotine gum (2 mg) for 7 w
2. Skills training for RP. 2 sessions in 2 w, then 4 weekly drop-in sessions. Included identification of high-risk situations and coping strategies, homework
3. Combined 1 and 2
OutcomesAbstinence for 4 w at 10½ m after quit date
Validation: CO < 8 ppm (2 people unable to attend assessment, based on self-report), Serum thiocyanate measured at 6 w only
Notes3 versus 1 for effect of RP component over NRT alone3 versus 2 tests for effect of NRT for initial cessation, not included
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomization method not described (married couples allocated to same condition)
Allocation concealment (selection bias)Unclear riskNo details given
Blinding of participants and personnel (performance bias)
All outcomes
High riskNo blinding reported. "Interpretation of this data is hampered by the lack of a placebo control condition". Unclear whether therapists aware of gum allocation
Blinding of outcome assessment (detection bias)
All outcomes
Low riskBiochemical validation used
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskLosses to follow-up not reported, all participants included

Killen 1990

MethodsSetting: Community, USA (Stanford Stop Smoking Project)
Recruitment: media advertisements for volunteers for S-H RP research programme. To be eligible for randomization, had to have quit for 48 h unaided. (Quit validated by CO < 9 ppm)
Participants1218 smokers who had quit for 48 h; 52% F, av age 43, av cigs/day 25
Interventions

4 × 3 factorial design crossing gum and S-H conditions:

Nicotine gum (2 mg) conditions:

1. Ad lib schedule, whenever strong need to smoke

2. Fixed schedule (1 piece/h for at least 12 h/day)

3. Placebo gum

4. No gum

S-H intervention was based on 16 specially written modules. All participants were given the first 'How to cope with the urge to smoke without smoking' booklet. Then randomly assigned to:

  • Self-selected-chose 7 more to receive in weekly mailings

  • Random-sent 7 modules at random

  • No modules-no further contact

OutcomesAbstinence at 12 m (7 day PP)
Validation: saliva cotinine < 20 ng/mL, except for participants who had moved away
NotesQuit rates for module/no-module conditions provided by authors. Gum conditions collapsed
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomization method not stated
Allocation concealment (selection bias)Unclear riskNo details given
Blinding of participants and personnel (performance bias)
All outcomes
Unclear risk"Assignment to gum condition was double-blind" but further information not provided
Blinding of outcome assessment (detection bias)
All outcomes
Low riskTreatment condition blinded, biochemical validation used
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskLosses to follow-up not reported, all participants included except 8 deaths

Killen 2006

MethodsSetting: Clinic, USA
Recruitment: community volunteers
Participants362 smokers ≥ 10 cigs/day, no current major depression
46% F, av age 45, av cigs/day 20, 25% previous bupropion use
InterventionsAll participants received open-label combination pharmacotherapy of bupropion 300 mg for 11 w, nicotine patch for 10 w. TQD day 7, 30 min individual RP skills training at 6 clinic visits
1. Bupropion 150 mg for 14 w
2. 2 w tapering bupropion, then placebo
Both arms had 4 further clinic visits during extended therapy
OutcomesAbstinence at 12 m (6 m post-EOT) (continuous). PP and 7-day relapse-free outcomes also reported
Validation: CO (10 people not required to provide samples)
NotesNew for 2009 update
PP outcomes favour placebo, but no outcomes showed significant effects
Approximately 52% were quit at the end of baseline therapy
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskPre-assigned random sequence stratified by gender, before open-label phase
Allocation concealment (selection bias)Low riskNot explicitly concealed but judged probable that it was
Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinded drugs provided to investigator; " ... [the pharmaceutical company]... packaged the treatment and then shipped the blinded drug to the investigator"
Blinding of outcome assessment (detection bias)
All outcomes
Low riskTreatment condition blinded, biochemical validation used
Incomplete outcome data (attrition bias)
All outcomes
Low risk10% lost to follow-up, included in ITT analysis

Klesges 1999

MethodsSetting: Air Force, USA
Recruitment: recruits undergoing basic military training (BMT)
Participants18010 recruits, 29% regular smokers before enforced abstinence during training. 28% F, av age 20
Interventions1. Single 50-min intervention during final week of training, 50/group, incl non-smokers. Discussed health effects, costs, social impact, role-play
2. Control: general health video
All participants exposed to 6 w smoking ban and shown 2 videos to preview primary intervention
OutcomesAbstinence at 12 m (not defined)
Validation: none
Relapse amongst baseline ex-smokers and initiation amongst non-smokers also reported
NotesResults not displayed graphically because denominators not explicit. No significant overall benefit. ICC small (0.004 for smokers)
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskCluster-randomized by training flight. 75% assigned to intervention, method of sequence generation not specified
Allocation concealment (selection bias)Low riskNot specified, but training flight allocation was independent of this trial, so potential for bias small
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNo blinding reported, control knowledge of intervention unclear, personnel knowledge of participant assignment not reported
Blinding of outcome assessment (detection bias)
All outcomes
Low riskAlthough no biochemical validation used, intervention was of low intensity with limited face-to-face contact, sample size was large, follow-up rate was high and self-report was via survey. Risk of differential misreport is low
Incomplete outcome data (attrition bias)
All outcomes
Low risk96% of available smokers reached

Klesges 2006

MethodsSetting: Air Force, USA
Recruitment: recruits undergoing basic military training (BMT)
ParticipantsSubgroup of ˜7525 regular smokers in intervention and ˜2639 in control
Interventions1. Two 1 h sessions during w 6 of BMT, emphasis on discrepancy between Air Force ideals and smoking. Barriers, role-playing. One sheet of NRT gum available for use at end of training
2. Same schedule, health-related and first aid videos
OutcomesAbstinence at 1 y (sustained from end of BMT)
Validation: none
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskCluster-randomized by training flight. 75% assigned to intervention, method of sequence generation not specified
Allocation concealment (selection bias)Low riskNot specified, but training flight allocation was independent of this trial, so potential for bias small
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot specified
Blinding of outcome assessment (detection bias)
All outcomes
High riskStaff who conducted follow-ups were not blinded to treatment assignment at follow-up; differential follow-up possible for participants who did not respond to survey and were contacted by telephone.
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskRandom subgroup targeted for follow-up, 86% reached. People lost to follow-up excluded because likely to be missing completely at random

Lando 1996

MethodsSetting: Community, USA
Recruitment: community volunteers
Participants1083 smokers who attended a smoking cessation clinic; 60% F, av age 45, av cigs/day 27
InterventionsAll participated in 15-session 8 w group cessation programme
1. Telephone counselling at 3, 9, 21 m. At each point, up to 3 calls could be made if requested
2. Control. No additional contact
OutcomesAbstinence at 34 m (12 m after EOT (7 day PP)). Also assessed at 6, 12 and 24 m
Validation: random half of quitters validated by saliva cotinine < 20 ng/mL at 12 m. 91% confirmed
NotesNot pooled with other studies. Analysis 9.1.1
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomization method not described
Allocation concealment (selection bias)Unclear riskNo details given
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskUnclear whether counsellors for group sessions were aware of participant allocation. Unclear if control group was aware of additional support offered to intervention group
Blinding of outcome assessment (detection bias)
All outcomes
Low riskBiochemical validation used in subsample with low level of discrepancies indicated, "difference between the intervention and comparison conditions in disconfirmation was not significant"
Incomplete outcome data (attrition bias)
All outcomes
Low risk> 95% reached at each follow-up, all participants included in analysis

Lifrak 1997

MethodsSetting: Substance abuse outpatient facility, USA
Recruitment: community volunteers
Participants69 smokers (≥1 pack/day); 62% F, av age 39, av cigs/day 25
InterventionsAll received nicotine patch (24 h, 10 w tapered dose)
1. Moderate intensity-4 meetings with nurse practitioner who reviewed S-H materials and instructed in patch use
2. High intensity. As 1 plus 16 weekly 45-min cognitive-behavioural RP therapy from clinical social worker or psychiatrist
OutcomesAbstinence at 12 m (1 w PP)
Validation: urine cotinine for some participants, but no corrections made for misreporting
NotesHigh-intensity participants attended median of 8¼ sessions
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomization method not described
Allocation concealment (selection bias)Unclear riskNo details given
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNo information provided
Blinding of outcome assessment (detection bias)
All outcomes
High riskIncomplete urinary cotinine samples collected, so not used to validate abstinence. Intervention group received significantly more intensive face-to-face contact, differential misreport possible.
Incomplete outcome data (attrition bias)
All outcomes
Low risk12 administrative dropouts/exclusions not included, treatment group not specified

Lowe 1997

MethodsSetting: Prenatal clinic, USA
Recruitment: volunteer recent quitters
Participants78 pregnant women who had quit within previous 3 m (9 exclusions and 19 lost to follow-up not included)
Age/smoking history not described
Therapists: health educator. Reinforcement provided by doctors and nurse trained at workshops
Interventions1. 10 min counselling with health educator. RP materials at 5th grade reading level, enhance social support with materials, chose 'buddy'. Reinforcement at routine visits by clinic staff
2. Usual care, incl nurse advice
OutcomesContinued abstinence at end of pregnancy (exact period NS)
Validation: saliva thiocyanate
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomization method not described
Allocation concealment (selection bias)Unclear riskNo details given
Blinding of participants and personnel (performance bias)
All outcomes
Low riskBlinding not relevant because of nature of the intervention (all relevant personnel involved in delivering intervention); any potential causes of performance bias could be considered deliberate elements of the intervention
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskBiochemical validation used
Incomplete outcome data (attrition bias)
All outcomes
Low riskGreater loss to follow-up in control, so losses to follow-up not included in denominators to give conservative RR
Other biasUnclear riskPotential contamination, "the issue of contamination, while monitored, is one that remains a concern"

Mayer 2010

Methods

Setting: Workplaces, Belgium

Recruitment: participants achieving abstinence in workplace-based smoking cessation programme, randomly assigned by workplace

Participants

275 adult attendees of workplace-based cessation programme who achieved 4 weeks continuous abstinence at 3 m after quit date (42 companies)

74% M, av age 40.6, more than 50% smoked 12 to 25 cpd, av FTND 6.5

Interventions

Smokers wishing to quit invited to join cessation program through companies (13 group sessions, nicotine patches provided). Then randomly assigned to RP interventions:

1. Workplace Group Counselling (WGC), conducted at work (company decided if during or after work hours), 90 min each. Groups of 5 to 10 participants

2. Proactive Phone Counselling (PPC), each session minimum of 10 min

Both programmes: 10 sessions (2 in month 1, monthly thereafter); participants have to pay 50 euros to participate (some companies decided to cover fees); content focused on participants' difficulties and provided psychological support where relevant

Outcomes

4 w continuous abstinence at 12 m post quit date (immediately after end of RP intervention)

Validation: CO < 10 ppm, urinary cotinine ≤ 317 ng/mL

Notes

New for 2013 update

Higher participation rate in PPC arm (81% to 95%) vs WGC arm (49% to 70%). Not included in an7 meta-analyses: 87/141 quit WGC, 77/134 PPC

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskCluster randomized by worksite. “Workplace randomization was based on using a single sequence of random assignments produced by a computer program”
Allocation concealment (selection bias)Unclear riskCompanies randomly assigned at end of cessation program, allocation concealment not described
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot specified
Blinding of outcome assessment (detection bias)
All outcomes
Low riskBiochemically validated abstinence
Incomplete outcome data (attrition bias)
All outcomes
Low risk5 participants lost to follow-up and counted as smokers
Other biasHigh riskHigher rates of abstinence detected in those with biochemically validated abstinence at enrolment (≤ 317 ng/mL). WGC arm had significantly more of these participants than PPC arm (96.4% vs 89.4%). Adjusted figures not provided

McBride 1999

MethodsSetting: Two managed care organisations, USA
Recruitment: pregnant smokers and recent quitters
Participants897 pregnant women (excludes miscarriages), 44% already quit, no minimum consumption
Av age 28, av cigs/day: 15 before pregnancy, 5 if still smoking
Interventions1. Prepartum intervention: letter tailored to baseline stage of change, health concerns and motivation, S-H book. After 28 w follow-up, sent RP kit
2. Telephone counselling calls, approx 2 w after S-H mailing, and 1 and 2 m later. Motivational interviewing approach. Av 8½ min
3. Pre/postpartum intervention: as 1, plus 3 calls within first 4 m postpartum, av 7.7 min, 3 newsletters
4. Control: S-H booklet only
OutcomesAbstinence at w 28 of pregnancy (analysis 1.1) and 12 m postpartum (7 day PP) (analysis 2.1). Also assessed at 8 w, 6 m postpartum
Validation: saliva cotinine requested by mail, < 20 ng/mL. Only self-reported rates, no difference in confirmation rates
NotesAbstinence at w 28 reported separately for baseline quitters
Relapse rate in 28 w quitters also reported. 1 versus 2 in analysis 1.2.1 and 1 versus 3 in 1.2.2, control group split to avoid double counting in pooled total. No significant benefit of postpartum intervention
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomization method not described
Allocation concealment (selection bias)Unclear riskNo details given
Blinding of participants and personnel (performance bias)
All outcomes
Low risk"The intervention was delivered via mail and telephone without involvement of prenatal health care providers". "Couselors were not involved in any follow-up survey activities"
Blinding of outcome assessment (detection bias)
All outcomes
Low riskBiochemical validation used, not reported: "Since there were no between-group differences in the proportion of saliva samples returned or the proportion confirmed, the primary trial outcomes were based on self-reported smoking status"
Incomplete outcome data (attrition bias)
All outcomes
Low riskNonresponders assumed to have relapsed

McBride 2004

MethodsSetting: Army Medical Center, USA
Recruitment: pregnant smokers and recent quitters with partners
Participants316 pregnant recent quitters, 267 continuing smokers (excludes miscarriages); av age 24, av cigs/day prepregnancy 13
InterventionsBoth interventions included prepartum and postpartum components, in addition to usual care
1. Women only (WO); 3 counselling calls in pregnancy, 3 postpartum, monthly. Motivational interviewing. Late pregnancy relapse prevention kit
2. Partner-assisted (PA); as WO, plus advice on using partner as coach, and 6 calls to partner. Cessation support for smoking partners
3. Usual care; provider advice and mailed pregnancy-specific S-H
OutcomesAbstinence at w 28 of pregnancy and 12 m postpartum (7-day PP). Also assessed at 8 w, 6 m postpartum
Validation: saliva cotinine requested by mail, no difference in return rates, disconfimation rates not given, only self-reported rates reported
NotesNew for 2009 update
End of pregnancy abstinence amongst baseline quitters, combining interventions 1 and 2 versus control in analysis 1.1. No significant effect of either intervention on end of pregnancy abstinence amongst baseline smokers. 12 m postpartum abstinence for those quit at end of pregnancy in analysis 1.2. Abstinence rates not given separately for those quit at randomization, but ⅔ of end-of-pregnancy quitters came from this category, and the prepartum interventions did not increase cessation
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomization method not stated
Allocation concealment (selection bias)Unclear riskNo details given
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNo blinding reported
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskBiochemical validation conducted but not used in outcome data. "Saliva return rates did not differ by condition at either follow-up", but rates of return low and level of misreport not specified
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskExcludes miscarriages, no other information on losses

Mermelstein 2003

MethodsSetting: Cessation clinic, USA
Recruitment: community volunteers for cessation programme
Participants341 quitters at the end of 7 w group cessation programme (non-abstinent subgroup not relevant to this review)
Demographics for all 771: 66% F, av age 43, av cigs/day 23
Interventions1. Tailored proactive telephone counselling calls from counsellor who provided cessation course. 3 weekly then 3 to 6 alternate w, 15 min each
2. Supportive but non-specific proactive counselling calls from counsellor, same schedule
OutcomesAbstinence at 15 m, 7-day PP
Validation: none
NotesAnalysis 4.1 but borderline to pool with other studies because both groups could constitute RP; primarily a test of content. Exclusion does not change finding
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskCluster-randomized by cessation group
Allocation concealment (selection bias)Unclear riskNot specified
Blinding of participants and personnel (performance bias)
All outcomes
Low risk"Counselors were kept blind to condition until the last group meeting"
Blinding of outcome assessment (detection bias)
All outcomes
Low riskBiochemical validation not used, but same intensity of contact in both groups, differential misreport unlikely
Incomplete outcome data (attrition bias)
All outcomes
Low risk96% of entire study provided data at all follow-ups

Morasco 2006

MethodsSetting: Prenatal clinic, USA
Recruitment: recent quitters
Participants33 pregnant recent quitters (subgroup of trial); av age 22, av cigs/day before quit 13
InterventionsAll participants received prompted provider advice and S-H
1. Individual counselling; 90-min psychotherapy session and bimonthly phone calls from mental health counsellors
2. Usual care
OutcomesAbstinence at end of pregnancy and 6 m postpartum (7-day PP)
Validation: CO ≤ 8 ppm
NotesNew for 2009 update. Baseline smoker results reported separately, not used in this review
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomization method not described
Allocation concealment (selection bias)Unclear riskNo details given
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNo details given
Blinding of outcome assessment (detection bias)
All outcomes
Low riskBiochemical validation used
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskParticipants lost to follow-up counted as smokers, but numbers lost to follow-up not broken down by group

Niaura 1999

MethodsSetting: Cessation clinic, USA
Recruitment: community volunteers
Participants120 smokers; 50% F, av age 44, av cigs/day 28
InterventionsAll participants received single brief individual counselling session 1 w before TQD and instructed to use ALA S-H manual 'Freedom from smoking for you and your family', CO measured. All interventions used 5 sessions over 2 w post TQD, led by PhD level therapists
1. Cognitive-behavioural with cue exposure (75-min sessions) imagined high-risk settings
2. Cognitive-behavioural with cue exposure and nicotine gum (90 min)
3. Brief cognitive-behavioural. Reviewed progress and reinforced use of S-H manual. (15-min sessions). Control for 1
4. Cognitive-behavioural and nicotine gum (60 min). Control for 2
OutcomesSustained abstinence, 12 m and all previous follow-ups (1, 3, 6 m)
Validation: CO < 8 ppm
NotesTest of imaginary cue exposure for RP. 1 and 2 vs 3 and 4 in analysis 7.1
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomization method not stated
Allocation concealment (selection bias)Unclear riskNo details given
Blinding of participants and personnel (performance bias)
All outcomes
Unclear risk"Counselors were kept blind to the relapse prevention condition to which subjects were assigned". Pts not blinded, and no placebo
Blinding of outcome assessment (detection bias)
All outcomes
Low riskBiochemical validation used
Incomplete outcome data (attrition bias)
All outcomes
Unclear risk80% completed follow-up, no group differences, all included in ITT analysis

Pbert 2004

MethodsSetting: Five community health clinics, USA
Recruitment: Low-income women receiving prenatal care and participating in Special Supplemental Nutrition Programme
Participants168 pregnant recent quitters (subgroup of trial); av age 26, av cigs/day 15 to 18 for whole sample
InterventionsSystem-level intervention
1. Training to implement guideline-based 4 A's approach for obstetric, paediatric and nutrition programme providers in the Community Health Centres, practice management system for screening and prompts, interclinic communication
2. No training, usual care from clinic providers
OutcomesAbstinence at delivery (30-day PP) assessed retrospectively at 1 m postpartum assessment, 6 m postpartum
Validation: saliva cotinine ≤ 20 ppm
NotesNew for 2009 update
Saliva collection was incomplete, and lesser agreement was noted between self-report and cotinine values in intervention group, although difference significant only at final follow-up. Not pooled with other studies. When non-responders were treated as smokers, the OR for not smoking at end of pregnancy was 0.95 (P = 0.95)
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskCluster-randomized by clinic, method not stated
Allocation concealment (selection bias)High riskClinics recruited participants after randomization, 1 control clinic dropped out because of poor recruitment, 2 clinics enrolled > 50% of participants
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot specified
Blinding of outcome assessment (detection bias)
All outcomes
Low riskBiochemical validation used
Incomplete outcome data (attrition bias)
All outcomes
Low riskHigher loss to follow-up in intervention (46/81, 57%) than control (37/77, 48%). ITT analysis reported

Powell 1981

MethodsSetting: Clinic, USA
Recruitment: community volunteers
Therapist: senior author
Participants51 quitters (2 treatment dropouts excluded); 57% F, av age 36, av cigs/day 29
InterventionsAll participants received the same cessation programme in a single group. Introductory meeting and 4 consecutive treatment meetings a week later, 1½ h. Systematic focus on skill development. Also used a novel aversive smoking exercise conducted at each session
Maintenance/RP conditions:
1. 4 w support group (number of meetings not specified)
2. Telephone contact system allowing participants to phone each other
3. No contact control
OutcomesAbstinence at 1 y, not defined
Validation: none
NotesArm 2 not shown in graphs, all arms had similar quit rates
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear risk'Randomly assigned' with deviations for scheduling conflict and to separate families and friends
Allocation concealment (selection bias)Unclear riskNo details given
Blinding of participants and personnel (performance bias)
All outcomes
Low riskSubjects randomly assigned to maintenance condition "at the end of the treatment phase", performance bias during treatment phase not likely
Blinding of outcome assessment (detection bias)
All outcomes
High riskNo biochemical validation used, intensity of contact different between conditions with some in person, differential self-report possible
Incomplete outcome data (attrition bias)
All outcomes
Low riskAll but one participant contacted at follow-up

Ratner 2000

MethodsSetting: Obstetric wards in 5 hospitals, Canada
Recruitment: postpartum women
Participants251 women who had given up smoking for at least 6 w before delivery; av age 28, av cigs/day 10, 74% first child
Interventions1. Counselling session in hospital + 8 telephone (weekly for 1 m, biweekly for 2 m). Skills training. S-H pamphlets, no-smoking materials. Therapists: trained nurse counsellors
2. Usual care
OutcomesContinuous abstinence 12 m postdelivery
Validation: CO < 10 ppm for participants interviewed in person. Data collectors blind
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk'Identification numbers randomly assigned to 2 groups, in blocks of 50, via a computer software package'
Allocation concealment (selection bias)Unclear riskNo details about sequence concealment
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskResearch assistants responsible for outcome assessment were blinded, further details not reported
Blinding of outcome assessment (detection bias)
All outcomes
Low riskBiochemical validation used at in-person follow-ups (89% of participants)
Incomplete outcome data (attrition bias)
All outcomes
Low riskDenominator excludes 13 not reached at follow-up. No differential dropout

Razavi 1999

MethodsSetting: Workplaces, Belgium
Recruitment: employee volunteers
Participants993 began cessation programme, 349 abstinent at 3 m, 344 entered RP phase. 38% F, av age 39
InterventionsInitial cessation programme of 7 fortnightly visits. Nicotine patch provided if FTQ score ≥ 5. Only quitters abstinent for 1 m enrolled in RP
1. 10 monthly sessions, incl group discussion and role-play led by professional counsellor
2. 10 sessions of group discussion led by former smokers
3. No RP
OutcomesAbstinence for 9 m from start of RP programme
Validation: CO < 10 ppm and urine cotinine≥ 317 ng/mL required
(Rates for CO and self-report alone also reported; higher than for doubly validated rates)
NotesInterventions 1 and 2 combined in analysis 4.1. Separate quit rates: Intervention 1. 59/135 (44%); Intervention 2. 33/88 (37.5%), difference not statistically significant
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskCluster-randomized by company, using random number and blinded list
Allocation concealment (selection bias)Low riskCompany allocation blinded and participants recruited before randomization
Blinding of participants and personnel (performance bias)
All outcomes
Low riskNo blinding reported but randomization once achieved cessation and cluster randomization by worksite, performance bias unlikely
Blinding of outcome assessment (detection bias)
All outcomes
Low riskBiochemical validation used
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskLosses to follow-up not reported, all randomly assigned participants included in analyses

Reitzel 2010

Methods

Setting: Texas, USA

Recruitment: pregnant women recruited through local health system or community advertisements

Participants

251 low-income women who quit smoking during pregnancy

Av age 24.6, av cpd 10.2 pre-quit, 92.4% quit smoking approx 8 w after pregnancy

Interventions

All participants received self-help materials and 5 to 10 min of US guideline-based brief relapse prevention advice

1. MAPS: 6 telephone-based counselling sessions at w 34 and 36 prepartum and at w 2, 4, 7 and 16 postpartum, using combined motivational enhancement and social cognitive approach

2. MAPS+: As per 1, plus 2 additional in-person counselling sessions at baseline and at w 8 postpartum

3. Control: usual care

Outcomes

Continuous abstinence at 8 and 26 w postpartum (defined as no smoking since delivery date)

Validation: CO < 10 ppm and/or cotinine < 20 ng/mL

Notes

New for 2013 update

80% of intervention participants received at least 4 calls

MAPS and MAPS+ combined for analysis in trial report; groups did not differ on baseline characteristics, completed calls, session length or percentage of participants abstinent

Number abstinent not provided, extrapolated from percentages given in trial report

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk"Following baseline data collection, participants were randomized by computer… using minimization"
Allocation concealment (selection bias)Low riskCentralised, see above
Blinding of participants and personnel (performance bias)
All outcomes
High riskNo blinding: "Neither participants nor research personnel was blind to treatment condition assignment following randomization"
Blinding of outcome assessment (detection bias)
All outcomes
Low riskSmoking status biochemically validated
Incomplete outcome data (attrition bias)
All outcomes
Low riskParticipants lost to follow-up counted as smokers in ITT analysis. Similar rates of dropout across groups (UC 23%; MAPS 32%; MAPS+ 24%)

Ruger 2008

MethodsSetting: Obstetric clinics, USA
Recruitment: pregnant women who smoked or had quit within 3 months of baseline
Participants57 pregnant recent quitters (subgroup of trial), av age of whole sample 26
Interventions1. Motivational interviewing at home visits (average 3). Tailored to stage of change, S-H materials
2. Usual care
OutcomesQuit at 6 months postpartum
Validation: salivary cotinine, but cutoff and percentage validated not specified
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskMethod not described
Allocation concealment (selection bias)High riskNo details given, but higher proportion of recent quitters in control (23%) than intervention (15%) suggests possible selection bias
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot specified
Blinding of outcome assessment (detection bias)
All outcomes
Unclear risk"Smoking status was verified biochemically by collecting saliva samples for saliva cotinine analysis", unclear whether validation completed, confirmation rates not reported
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskDropouts not included in reported denominators, included as smokers in meta-analysis

Schmitz 1999

MethodsSetting: Hospital, USA
Recruitment: women with or at risk of coronary artery disease (CAD)
ParticipantsTwo separate samples recruited:
1. 53 inpatients with CAD who stopped smoking during hospitalisation and wanted to stay quit
2. 107 women volunteering for cessation treatment who had > 1 CAD risk factor
Therapists: 2 smoking counsellors and 2 clinical psychology interns
Interventions1. Coping skills RP, 6 × 1 h, incl stress management, homework
2. Health Belief model, 6 × 1 h smoking-related health information related to disease state or CAD profile. Focus on benefits of stopping
OutcomesPP abstinence at 6 m
Validation: CO < 9 ppm, urine cotinine < 10 ng/mL
Not all quitters tested, confirmation rates not reported
NotesInpatient subgroup in quitters section, analysis 2.1; CAD risk group in trials in smokers, matched control section, analysis 7.1
Quit rates were lower in the CAD sample than in the at-risk group
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomization method not described
Allocation concealment (selection bias)Unclear riskNo details given
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot specified
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskBiochemical validation used, but not all quitters tested and confirmation rates not reported
Incomplete outcome data (attrition bias)
All outcomes
Low riskPostrandomization dropouts who did not complete baseline and begin treatment were not included in any data, other losses to follow-up counted as smokers

Schroter 2006

MethodsSetting: Four workplaces, Germany
Recruitment: volunteer employees
Participants79 smokers (≥ 10 cigs/day); 42% F, av age 40, av cigs/day 24
InterventionsBoth conditions provided 6 × 90 min sessions over 8 w in groups of 8 to 12 led by qualified providers
1. RP; skills training, planning and practising coping strategies
2. Standard behavioural cessation course with focus on positive changes obtained through abstinence. Included self-monitoring, environmental cue control, problem-solving skills
OutcomesContinuous abstinence at 12 m, not defined further
Validation: none
NotesNew for 2009 update
Compares RP with matched standard programme
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskCluster-randomized, 2 groups in each workplace, researchers randomly assigned 1 to each condition, no further details
Allocation concealment (selection bias)Unclear riskNo details given
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot specified
Blinding of outcome assessment (detection bias)
All outcomes
Low riskNo validation used, but similar amount of interaction in both groups suggests differential misreport unlikely
Incomplete outcome data (attrition bias)
All outcomes
Low risk47% attrition reported, but all participants included in analyses

Secker-Walker 1995

MethodsSetting: Private and public prenatal clinics, USA
Recruitment: women at 1st prenatal visit
Participants165 women previously smoking 1+ cigs/day who had quit since start of pregnancy (excludes 10 adverse pregnancy outcomes)
Av age 25
Interventions1. Individual counselling focusing on pros and cons, problem solving, skills rehearsal. 10 to 15 min at 1st, 2nd and 3rd prenatal visit, 36 w and 6 w postpartum. (93% received postpartum session)
2. Usual care control
OutcomesAbstinence at 36 w pregnancy (analysis 1.1) and at 8 to 54 m postpartum (analysis 1.2). Follow-up point varied
Validation: at 36 w, cotinine/creatinine ratio > 80 ng/mg, but some missing data, no validation postpartum
NotesSensitivity analysis excluding losses to follow up does not alter results
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomization method not stated
Allocation concealment (selection bias)Unclear riskNo details given
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNo details given, possible care providers were aware of participants' assignment
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSelf-report used postpartum and for some women at 36 w ("We included the 40 women who reported not smoking, but were missing 36-week cotinine/creatinine ratios, in the non-smoking group, rather than count them as having relapsed".) Reason for missing validation data at 36 w not reported, group assignment of participants missing data not clear, differential misreport possible
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNo significant differences in loss to follow-up at 1 y (35%). Numbers randomly assigned used in analyses, but restricting to numbers available for follow-up does not alter findings

Secker-Walker 1998

MethodsSetting: Prenatal clinic, USA
Recruitment: women at 1st prenatal visit
Participants116 women previously smoking 1+ cigs/day who self-reported quitting since start of pregnancy (excludes 9 adverse pregnancy outcomes). 19 of the women showed evidence of smoking at 1st prenatal visit
Interventions1. Structured intervention from physician, individual counselling by nurse counsellor, 1st, 2nd, 3rd, 5th, 36 w prenatal visits
2. Usual care from physician, prompted at 1st visit
OutcomesSustained abstinence at 36 w pregnancy (analysis 1.1), 1 y postpartum (analysis 1.2)
Validation: CO ≤ 6 ppm at 36 w, also urine cotinine ≤ 500 ng/mL but some missing data
NotesProcess analysis showed counselling to have been received fairly consistently but fell to 66% at 5th visit
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskMethod not described
Allocation concealment (selection bias)Unclear riskNo details given
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNo details given
Blinding of outcome assessment (detection bias)
All outcomes
Low riskBiochemical validation used at 36 w and differential misreport not identified. Similar rates abstinent at 1 y postpartum, differential misreport not likely at final follow-up
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo significant differences in loss to follow up at 1 y (33%). Numbers randomly assigned, excl adverse pregnancy outcomes used in denominators

Segan 2011

Methods

Setting: Victoria, Australia Quitline

Recruitment: callers to Quitline

Participants

698 smokers or recent ex-smokers calling Victoria, Australia, Quitline and abstinent for at least 1 w (1444 randomly assigned, but study conducted only in those achieving abstinence)

54% F, av age 37, av cpd 21

Interventions

Participants received same callback service before quitting and same service in first month postquit (revised version of standard Quitline service: 4 calls in first m postquit to help deal with daily cravings and withdrawal). Service based on 3 Tasks of Quitting Framework. Both groups receive counselling for first 2 tasks

1. 4 to 6 additional calls 1 to 3 m post quitting to actively assist with learning to enjoy and value a smoke-free lifestyle (task 3), initiated when participant reported less than daily cravings or completed 4 standard calls (whichever came first)

2. No additional calls

Outcomes

12 m continuous abstinence

Validation: none

Notes

New for 2013 update

n not provided, data extrapolated from percentages given. Only those participants abstinent for 1 w or longer included in final analyses

74% of intervention grp received extra calls, on av 1.7 more calls postquit than control group

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk"Randomization was controlled by an automated function in the Quitline client management database"
Allocation concealment (selection bias)Low riskCentralised, see above
Blinding of participants and personnel (performance bias)
All outcomes
High risk"Follow-up interviewers were blinded to participant treatment condition, although for the four-month follow-up blinding was lost…" Participant and provider unblinded
Blinding of outcome assessment (detection bias)
All outcomes
Low riskNo biochemical validation, but no face-to-face contact, so differential misreport judged to be unlikely
Incomplete outcome data (attrition bias)
All outcomes
Low riskSimilar rate lost to follow-up in both groups (28% control; 30% intervention), participants lost to follow-up counted as smokers. Analysis excluding participants lost to follow-up did not affect final comparisons
Other biasHigh riskProbable lack of differentiation between the two conditions and risk of contamination: “In practice, the first couple of integration callbacks typically replaced the last call or two of the standard service (rather than adding on to it)…. Usual care participants received on average 2.2. calls after reaching the point of less than daily cravings, which provided ample opportunity for contamination...”

Severson 1997

MethodsSetting: 49 private paediatric practices, USA
Recruitment: mothers attending for well baby visits
Participants1026 ex-smoking mothers (intervention also given to smoking mothers, not relevant to this review)
Therapists: paediatricians.
25 intervention practices, 23 control
Interventions1. Information pack, including a letter from paediatrician on risks of passive smoking, provided by birth hospital, and extended support (counselling plus follow-up at 2, 4 and 5 m visits) and materials (incl video tape, written materials, signs, magnets, bib)
2. Information pack only
OutcomesSustained abstinence at 12 m (7-day PP at 6 and 12 m)
Validation: none
NotesStudy design allowed for clustering in calculating sample size. ICC proved to be low. Use of a corrected odds ratio, which did not show a significant benefit, did not change conclusions (sensitivity analysis using inverse variance)
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskCluster-randomized by practice, method not described
Allocation concealment (selection bias)Unclear riskMethod of allocating practices not described. All eligible patients enrolled in study, "because the survey information was anonymous, and because smoking counselling was considered to be standard medical practice, the study was exempted from the requirements for obtaining informed consent"
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskParticipants not aware enrolled in study, so blinding not applicable. Unclear whether study personnel (administering surveys) were blinded.
Blinding of outcome assessment (detection bias)
All outcomes
Low riskNo biochemical validation but cluster-randomized by practice, followed up anonymously via survey, differential misreport unlikely
Incomplete outcome data (attrition bias)
All outcomes
Low riskLosses to follow-up (31% in each group) assumed to have relapsed, attrition analyses performed

Sheffer 2010

Methods

Setting: Quitline for Arkansas, USA

Recruitment: all participants calling the Quitline within a set amount of time were included

Participants

All Arkansas Quitline callers whose primary form of tobacco use was smoking who ended treatment (completing treatment or ending prematurely) within the set period and did not re-enter counselling within 2 years of index episode (n = 892)

35% M, av age 43, av cpd not specified, mean FTND 7

Interventions

1. Intervention: 8 "Forever Free" booklets (aimed at relapse prevention) mailed to all Quitline callers who ended treatment (within given 6 w period)

2. Nothing mailed to callers (all participants who consecutively ended treatment 1 month before or 1 month after intervention group)

All participants received standard Quitline service (av 6 weekly structured CBT sessions 20 to 30 min each); nicotine patches provided free of charge

Outcomes

7 d PP at 6 m after discontinuation of treatment

Validation: none

Notes

New for 2013 update

Quasi-randomized; baseline imbalances between groups, adjusted OR available

Intervention did not improve quit rates for participants receiving at least 1 session of counselling and nicotine patches but doubled abstinence rate for those unwilling/unable to receive nicotine patches at 6 m

n not provided, extrapolated from percentages reported

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)High riskQuasi-randomized. "The 'Forever Free' booklets were mailed to all quitline callers who ended treatment during a six-week period. For comparison, we included quitline callers whose treatment ended during the months immediately prior and succeeding the 6-week intervention period"
Allocation concealment (selection bias)High riskSee above
Blinding of participants and personnel (performance bias)
All outcomes
Low risk"Quitline staff including tobacco treatment specialists and follow-up interviewers were unaware that some participants had received additional materials"
Blinding of outcome assessment (detection bias)
All outcomes
Low riskNo biochemical validation but no additional personalised contact received by intervention group, so differential levels of misreport unlikely
Incomplete outcome data (attrition bias)
All outcomes
Low riskSimilar rates of dropout in both groups (34.7% intervention, 40.0% control); participants lost to follow-up counted as smokers

Shoptaw 2002

MethodsSetting: Three narcotics treatment centres, USA
Recruitment: volunteers on methadone maintenance
Participants175 smokers (≥ 10/day); 33% F av age 43 to 45, av cigs/day approx 22
InterventionsAll participants received 21-mg nicotine patch for 12 w. Factorial design crossing contingency management, arms collapsed
1. Group counselling: 12 × 1 h weekly sessions, incl mood management
2. Control: NRT alone
OutcomesPP abstinence at 12 m
Validation: CO ≤ 8 ppm, urine cotinine < 30 ng/mL
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandomization using urn technique
Allocation concealment (selection bias)Low riskNot described but use of urn technique makes it probable that allocation concealed
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot reported
Blinding of outcome assessment (detection bias)
All outcomes
Low riskBiochemical validation used
Incomplete outcome data (attrition bias)
All outcomes
Low riskNumber lost to follow-up not reported, but all missing included as smokers, and study reports, "no statistically significant differences across the four treatment conditions for breath samples and urine samples"

Smith 2001

MethodsSetting: Clinic, USA
Recruitment: community volunteers
Participants677 smokers (> 10/day) attempted quit for 1 w; 57% F, av age 42; av cigs/day approx 25
InterventionsAll participants had attended 3 brief (5 to 10 min) individual counselling sessions pre-quit, quit day and 8 days post TQD, + nicotine patches (8 w) + NCI booklet, 'Clearing The Air'
1. Cognitive-behavioural skills training, × 6 from 1 w post TQD, incl managing negative affect, homework, manual
2. Motivational interviewing, supportive group counselling, × 6 from 1 w post TQD. No homework or manual
3. No further intervention
OutcomesAbstinence at 12 m (7-day PP)
Validation: CO < 10 ppm
Notes1 versus 3 in analysis 4.1, including 2, does not alter findings; 17.6% quit in 1, 18.8% in 2. No evidence found for hypothesised differences in relative efficacy for smokers at high or low risk of relapse. High-risk smokers expected to do better with motivational intervention
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomly assigned 1 w after TQD, stratified by ± any smoking post TQD. Method not stated
Allocation concealment (selection bias)Unclear riskNo details given
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskParticipants randomly assigned after receiving pre-quit interventions. No further details provided
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskBiochemical validation used
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNumber lost to follow-up not reported, all missing included as smokers

Stevens 1989

MethodsSetting: HMO, USA
Recruitment: HMO member volunteers
Participants587 smokers who successfully abstained from smoking for 4 days after a 4-day intensive cessation programme
InterventionsBoth group conditions met for 3 × 2 h weekly meetings
1. Skills condition. Development and active rehearsal of coping strategies
2. Discussion condition. Social support meetings without rehearsal of strategies
3. No further treatment control
OutcomesAbstinence at 1 y, no tobacco use in previous 6 m
Validation: saliva thiocyanate < 0.8 mg/mL or cotinine < 5 ng/mL
NotesStudy hypothesis that discussion control would not increase rates, so in main analysis 1 versus 2 + 3
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskPredetermined random number list
Allocation concealment (selection bias)Unclear riskNot explicit that list concealed, although likelihood of selection bias judged to be small
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSubjects randomly assigned after initial treatment phase, no further information provided
Blinding of outcome assessment (detection bias)
All outcomes
Low riskBiochemical validation used. Staff following up non-attenders at 1 y meeting blind to treatment assignment
Incomplete outcome data (attrition bias)
All outcomes
Low riskLoss to follow-up 6.6% overall, non-significantly higher in control. Dropouts included in analysis

STRATUS-WW 2006

MethodsSetting: Australia, Canada, USA, setting type not reported but presumably clinic
Recruitment: not stated
Participants5055 adult smokers (> +18) motivated to quit. Randomly assigned to rimonabant 5 mg (N = 2026) or rimonabant 20 mg (N = 3029)
50% M, 88.8% W, mean age 44.1, av CPD 23.6, mean y smoking 24.1, mean quit attempts 4.1, mean FTND score 5.4, 31.7% with FTND score > 7. Mean BMI 27.8
InterventionsPhase 1: cessation trial: participants randomly assigned to rimonabant 5 mg [R5] (N = 2026) or rimonabant 20 mg [R20] (N = 3029) for 10 w, with TQD at day 15. Cessation rates at EoT: R5: 644/2026 (31.8%); R20 1017/3029 (33.6%), difference non-significant; Quitters eligible for phase 2 if: (a) self-reported abstinence for 7+ days, (b) CO ≤ 10 ppm, and (c) compliance level of 80%+ in last 4 w of phase 1
Phase 2: Relapse prevention: re-randomly assigned 644 quitters in R5 group to (i) R5 (N = 322) or (ii) placebo (N = 322), and 1017 quitters in R20 group to (i) R5 (N = 335) or (ii) R20 (N = 340) or (iii) placebo (N = 342). All groups received treatment for a further 42 w.
Behavioural support: not reported
OutcomesPrimary outcome: time to relapse for quitters from w 10 to 32. Relapse defined as ≥ 7 consecutive days of smoking (even a puff), or ≥ 2 consecutive days with ≥ 5 cigs (even a puff) smoked per day
Long-term follow up: 52 w, 104 w
Secondary outcome: time to relapse for quitters from w 10 to 52
Other outcomes: weight change; fasting HDL-cholesterol, triglycerides; safety, adverse events
Validation: phase 1: expired CO < 10 ppm; phase 2: not reported
Notes

New for 2013

Two-year follow-up data were not reported. Results not published and hence are limited, data not available on phase 1 R5 group
Trial was funded by the manufacturer, Sanofi Aventis

Percentage abstinent at 12 m very similar in R5 and R20 phase II groups (41.8 vs 41.5), combined in meta-analysis

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNot stated
Allocation concealment (selection bias)Unclear riskNot stated
Blinding of participants and personnel (performance bias)
All outcomes
Unclear risk"Double-blind", no further information provided
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information reported
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNot reported

Tonstad 2006

MethodsSetting: Cessation clinics in 7 countries. 6 sites in United States
Recruitment: smokers of ≥10/day for cessation phase
Participants1210 adults previously smoking ≥ 10/day, quit for at least 1 w after 12 w open-label varenicline
Interventions1. Varenicline 1 mg × 2 daily for 12 w with 5 clinic visits
2. Placebo
OutcomesSustained abstinence for 9 m at 1 y
Validation: CO ≥ 10ppm
NotesThe quit rate after the open-label phase was 64%
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskCentralised computer-generated randomization
Allocation concealment (selection bias)Low riskBased on use of centralised allocation
Blinding of participants and personnel (performance bias)
All outcomes
Low risk"Double-blind treatment phase"; "participant blinding was maintained during this [non-treatment follow-up] phase"
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskDouble-blind and biochemical validation used
Incomplete outcome data (attrition bias)
All outcomes
Low riskHigher loss to follow-up in controls due to relapse, dropouts counted as smokers

van Osch 2008

Methods

Setting: participants in national Quit and Win contest, Netherlands

Recruitment: e-mail to Quit and Win participants

Participants

1566 participants in national Quit & Win contest (daily smokers, smoking for at least 1 year, 18 years or older)

60.8% F, av age 36.2, av cpd 18.5, average length of smoking 19.1 years

Interventions

Quit and Win contest includes 1 m cessation period, incl computer-tailored cessation advice and telephone counselling

Intervention: participants asked to formulate three coping plans when completing baseline survey

Control: baseline survey only (not prompted to formulate coping strategies)

Outcomes

Continuous abstinence and 7 days PP at 7 m

Validation: none, although participants had buddies and were informed that biochemical abstinence would be performed for contest winners

Notes

New for 2013 update

Unclear how abstinence data were obtained

Including only respondents increases evidence of effect

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)High risk"Based on odd or even registration numbers"
Allocation concealment (selection bias)Unclear riskCentralised, but unclear whether participants aware of their registration numbers
Blinding of participants and personnel (performance bias)
All outcomes
Low riskNo blinding reported, but because of the nature of the intervention, performance bias unlikely
Blinding of outcome assessment (detection bias)
All outcomes
Low risk'Buddy' validation and knowledge of biochemical validation would be used for any contest winners, nature of intervention makes differential misreport unlikely
Incomplete outcome data (attrition bias)
All outcomes
High riskVery high rates of dropout at 7 m (64% control, 63% intervention). "The relatively high attrition suffered across the two follow-up measurements may restrict validity of the results and may have caused biases in reported abstinence rates"

Van't Hof 2000

MethodsSetting: Six hospitals, USA
Recruitment: women at time of delivery
Participants277 women who had quit during pregnancy, cotinine verified as not smoking at recruitment (excludes 10 not followed up for a variety of reasons). Av age 25, previous cigs/day not reported. 65% were very confident of remaining quit
Interventions1. 15 to 30 min of RP counselling from Visiting Nurse after baseline interview. Reinforcement by paediatric care provider at 2 w, 2 m, 4 m well baby clinics, written materials. Chart sticker used to prompt intervention
2. Usual care, baseline assessment from Visiting Nurse
OutcomesAbstinence at 6 m (assume PP)
Validation: none (assessment by phone, no details of blinding of assessor)
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomized, method not described
Allocation concealment (selection bias)Unclear riskNo details given
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNo details given
Blinding of outcome assessment (detection bias)
All outcomes
High riskNo biochemical validation, intervention participants received more face-to-face contact than control group, no details of blinding of assessor, differential misreport possible
Incomplete outcome data (attrition bias)
All outcomes
Low riskA sensitivity analysis including losses to follow-up does not change direction or significance of effect

Wetter 2011

  1. a

    RP = relapse prevention; TQD = target quit day;
    av = mean average; F = female; M = male; NS = not stated;
    s = seconds; min = minutes; m = months; w = weeks; y = years;
    FTQ = Fagerström Tolerance Questionnaire; FTND = Fagerström Test for Nicotine Dependence; NRT = nicotine replacement therapy; S-H = self-help;
    PP = point prevalence abstinence (abstinent at that time but not necessarily continuously since treatment); EOT = end of treatment;
    CO = carbon monoxide; ppm = parts per million;
    CBT = cognitive-behavioural therapy;
    HMO = health maintenance organisation; ALA = American Lung Association; NCI = National Cancer Institute;
    CABG = coronary artery bypass graft; MI = myocardial infarction; MDD = major depressive disorder; and
    ICC = Intraclass correlation.

Methods

Setting: Seattle, WA, USA

Recruitment: community volunteers

Participants

302 female smokers, 18 to 70 years old, smoking at least 10 cpd

Av age 43, av cpd 20.6, av FTND 5.2

Interventions

All participants received 6 w nicotine patch (21 mg/d); 2 group counselling sessions pre-quit and three postquit (through day 7); ecological momentary assessment (EMA) procedures for week immediately following quit date

1. 1 m computer-delivered treatment (CDT) on palmtop computers (3 modules: managing urge, treatment info and motivational messages) and EMA

2. EMA only for 1 m postquit date

Outcomes

Repeated 7 days PP (day 35, month 6, month 12)

Validation: CO < 10 ppm

Notes

New for 2013 update

Trial report provides only OR and adjusted OR (no raw data), n provided by authors

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk"the study biostatistician generated the randomization sequence"
Allocation concealment (selection bias)Unclear riskMethod not specified
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskBlinding not specified, unclear whether participants aware of additional element offered to intervention group
Blinding of outcome assessment (detection bias)
All outcomes
Low riskSmoking status biochemically validated
Incomplete outcome data (attrition bias)
All outcomes
Low riskDropouts counted as smokers in ITT analysis, similar number lost to follow-up in each group at 12 m (21 dropouts control, 19 dropouts treatment)

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
  1. a

    RP = relapse prevention; CBT = cognitive-behavioural therapy; w = weeks.

Adams 2011Only 2 months follow-up
Allen 2007Only 12 w follow-up
Alterman 2001Considered for inclusion because comparison of different intensity interventions. No mention of RP
Bottausci 1995Small trial, < 10 participants per condition
Brown 2001Considered for inclusion because comparison of different intensity interventions. Intervention focus was on use of CBT for treatment of depression. Relapse mentioned only in text
Carmody 1988Only 3 m follow-up reported. No significant differences at this point
Cinciripini 2000Not possible to distinguish RP from cessation components
Copeland 2006Evaluated a weight management programme for preventing relapse; see separate Cochrane review
Davis 1995Short follow-up, only 12 participants
DiSantis 2010Pilot study with only 1 m follow-up
Dooley 1992Only 3 m follow-up reported. No significant differences at this point
Dubren 1977Only 1 m follow-up reported
Dunphy 2000Only 4 to 8 w follow-up after delivery and intervention
Elfeddali 2012Participants randomly assigned before quitting, no cessation intervention provided to controls, so test of an Internet cessation programme. Not RP
Evins 2011Only 60-day follow-up
Feeney 2001Not explicitly described as an RP intervention, and the control condition has low implementation of the basic cessation programme
French 2007Not randomized
Froelicher 2000Describes a trial in progress, no intervention results
Garvey 2012Considered for inclusion because of frontloading of counselling sessions in one group. No mention of RP
George 2000Tested a specialised group therapy intervention for people with schizophrenia compared with a standard programme. Included other components in addition to RP
Goldstein 1989Considered for inclusion because comparison of different intensity interventions. No mention of RP
Gruder 1993Not possible to distinguish between RP and cessation components
Hall 1994Considered for inclusion because comparison of different intensity interventions. Primary focus was on CBT for depression as adjunct to cessation intervention. No mention of RP
Hall 1996Considered for inclusion because comparison of different intensity interventions. Primary focus was on mood management as adjunct to cessation intervention. No mention of RP
Hall 1998Considered for inclusion because comparison of different intensity interventions. No mention of RP
Hall 2011Considered for inclusion because study evaluates extended therapy. Not RP
Klesges 1987Randomization and analysis by worksite, number of individuals in each treatment condition not given. A non-significant difference favoured RP
Lando 1997Considered for inclusion because comparison of different intensity interventions. No mention of RP
Macleod 2003Considered for inclusion because comparison of different intensity interventions. No mention of RP
Miller 1997Hospital intervention included RP components but excluded because no information on smoking status of participants, and intervention similar in other respects to other inpatient trials. Also compared 2 intensities of telephone follow-up but these were not described as RP
Phillips 2012Only 8 w follow-up
Reid 1999Considered for inclusion because comparison of different intensity interventions. No mention of RP
Solomon 2000Considered for inclusion because comparison of different intensity interventions. No mention of RP
Storro 2008Controlled cohort study of postpartum intervention, not randomized
Tonstad 2013Test of vaccine versus placebo. Effect of pharmacotherapy postquit confounded with pharmacotherapy before quitting
Yoon 2009Only 2 w follow-up
Zelman 1992Considered for inclusion because comparison of different intensity interventions. No mention of RP

Characteristics of ongoing studies [ordered by study ID]

Jung 2010

Trial name or titleGetting Physical on Cigarettes - Smoking Cessation & Relapse Prevention
MethodsRCT
Participants420 adult female smokers smoking more than 10 cpd for past 2 years
InterventionsFollowing a 14-week supervised exercise programme, randomly assigned to one of four 'home-based' conditions: (a) exercise maintenance, (b) exercise maintenance plus relapse prevention booklet, (c) relapse prevention booklets plus contact, (d) contact only
OutcomesPrimary outcome is continuous abstinence at 3 and 12 months after the initial 14-week treatment programme
Starting dateOctober 2009
Contact informationDr Harry Prapavessis, hprapave@uwo.ca
NotesNCT01305447

NCT00621777

Trial name or titleA study of varenicline for prevention of relapse to smoking in patients with schizophrenia
MethodsRandomized double-blind placebo-controlled trial
Participants274 smokers with schizophrenia or schizoaffective disorder
Interventions12 weeks open-label varenicline, + 40 weeks randomly assigned to varenicline or placebo
Outcomes7-Day PPA at w 53 (12 w cessation treatment + 40 w relapse prevention treatment), safety/efficacy
Starting dateFebruary 2008
Contact informationAE Evins
Notes 

Williams 2011

Trial name or titleThe Smoker's Health Project
MethodsPragmatic comparative effectiveness trial of three self-determination theory (SDT)-based intensive tobacco dependence interventions
Participants818 smokers 18 or older who have smoked at least 100 cigs in lifetime and 5+ cpd over past 4 w
Interventions

1. Community care (6 m SDT-based intervention)

2. Extended need support (SDT intervention extended to 12 m, important other trained)

3. Harm reduction (as per 2 + recommends medication use for participants who do not want to stop smoking completely
within 30 d but who are willing to reduce their cigarette use by half)

OutcomesPrimary outcome is prolonged tobacco abstinence at 1 year posttreatment (2 years post randomization)
Starting dateNot specified
Contact informationGeoffrey Williams, Geoffrey_Williams@URMC.Rochester.edu
NotesNCT00178685

Ancillary