Behavioural interventions as adjuncts to pharmacotherapy for smoking cessation

  • Review
  • Intervention

Authors


Abstract

Background

Effective pharmacotherapies are available to help people who are trying to stop smoking, but quitting can still be difficult and providing higher levels of behavioural support may increase success rates further.

Objectives

To evaluate the effect of increasing the intensity of behavioural support for people using smoking cessation medications, and to assess whether there are different effects depending on the type of pharmacotherapy, or the amount of support in each condition.

Search methods

We searched the Cochrane Tobacco Addiction Group Specialised Register in July 2012 for records with any mention of pharmacotherapy, including any type of NRT, bupropion, nortriptyline or varenicline that evaluated the addition of personal support or compared two or more intensities of behavioural support.

Selection criteria

Randomized or quasi-randomized controlled trials in which all participants received pharmacotherapy for smoking cessation and conditions differed by the amount of behavioural support. Controls could receive less intensive personal contact, or just written information. We did not include studies that used a contact matched control to evaluate differences between types or components of support. We excluded trials recruiting only pregnant women, trials recruiting only adolescents, and trials with less than six months follow-up.

Data collection and analysis

Search results were prescreened by one author and inclusion or exclusion of potentially relevant trials was agreed by both authors. Data were extracted by one author and checked by the other.

The main outcome measure was abstinence from smoking after at least six months of follow-up. We used the most rigorous definition of abstinence for each trial, and biochemically validated rates if available. We calculated the risk ratio (RR) and 95% confidence interval (CI) for each study. Where appropriate, we performed meta-analysis using a Mantel-Haenszel fixed-effect model.

Main results

Thirty-eight studies met the inclusion criteria with over 15,000 participants in the relevant arms. There was very little evidence of statistical heterogeneity (I² = 3%) so all studies were pooled in the main analysis. There was evidence of a small but statistically significant benefit from more intensive support (RR 1.16, 95% CI 1.09 to 1.24) for abstinence at longest follow-up. All but two of the included studies provided four or more sessions of support. Most trials used nicotine replacement therapy. Significant effects were not detected for studies where the pharmacotherapy was nortriptyline (two trials) or varenicline (one trial), but this reflects the absence of evidence. In subgroup analyses, studies that provided at least four sessions of personal contact for the intervention and no personal contact for the control had slightly larger effects (six trials, RR 1.25, 95% CI 1.08 to 1.45), as did studies where all intervention counselling was via telephone (six trials, RR 1.28, 95% CI 1.17 to 1.41). Weaker evidence for a benefit of providing additional behavioural support was seen in the trials where all participants, including those in the control condition, had at least 30 minutes of personal contact (18 trials, RR 1.11, 95% CI 0.99 to 1.25). None of the differences between subgroups were significant, and the last two subgroup analyses were not prespecified. No trials were judged at high risk of bias on any domain.

Authors' conclusions

Providing behavioural support in person or via telephone for people using pharmacotherapy to stop smoking has a small but important effect. Increasing the amount of behavioural support is likely to increase the chance of success by about 10 to 25%, based on a pooled estimate from 38 trials. A subgroup analysis of a small number of trials suggests the benefit could be a little greater when the contrast is between a no contact control and a behavioural intervention that provides at least four sessions of contact. Subgroup analysis also suggests that there may be a smaller incremental benefit from providing even more intensive support via more or longer sessions over and above some personal contact.

Résumé scientifique

Interventions comportementales associées à la pharmacothérapie pour le sevrage tabagique

Contexte

Des pharmacothérapies efficaces sont disponibles pour aider les gens à arrêter de fumer, mais le sevrage peut néanmoins être difficile et un soutien comportemental intensif peut augmenter le taux de réussite.

Objectifs

Évaluer l'effet d'un soutien comportemental accru pour les personnes utilisant des médicaments de sevrage tabagique et déterminer si les effets sont différents selon le type de pharmacothérapie ou la quantité de soutien.

Stratégie de recherche documentaire

En juillet 2012, nous avons effectué une recherche dans le registre spécialisé du groupe Cochrane sur le tabagisme pour trouver des publications mentionnant la pharmacothérapie, dont tous les types de TSN, le bupropion, la nortriptyline ou la varénicline et évaluant l'ajout d'un soutien personnel ou comparant au moins deux niveaux de soutien comportemental.

Critères de sélection

Essais contrôlés randomisés ou quasi-randomisés au cours desquels tous les participants recevaient une pharmacothérapie pour le sevrage tabagique et bénéficiaient de différents niveaux de soutien comportemental. Les groupes témoins pouvaient bénéficier d'un contact personnel moins intensif, ou simplement d'informations écrites. Nous n'avons pas inclus les études dont le groupe témoin bénéficiait également d'un contact et qui visaient à évaluer les différences entre les types ou les composants du soutien. Nous avons exclu les essais recrutant uniquement des femmes enceintes, uniquement des adolescents ou dont la durée de suivi était inférieure à six mois.

Recueil et analyse des données

Les résultats de la recherche ont été préfiltrés par un auteur et le choix d'inclure ou d'exclure les essais potentiellement pertinents a été fait par les deux auteurs. Les données ont été extraites par un auteur et vérifiées par le second.

Le principal critère de jugement était l'abstinence tabagique après un suivi d'au moins six mois. Nous avons utilisé la définition la plus rigoureuse de l'abstinence pour chaque essai et les taux validés biochimiquement lorsqu'ils étaient disponibles. Nous avons calculé le risque relatif (RR) et l'intervalle de confiance (IC) à 95 % pour chaque étude. Le cas échéant, nous avons effectué une méta-analyse au moyen d'un modèle à effets fixes de Mantel-Haenszel.

Résultats principaux

38 études remplissaient les critères d'inclusion, avec plus de 15 000 participants dans les groupes pertinents. Il n'y avait que peu de preuves de l'hétérogénéité statistique (I² = 3 %), c'est pourquoi toutes les études ont été regroupées dans l'analyse principale. Les données montraient qu'un soutien plus intensif favorisait légèrement, mais de façon statistiquement significative (RR = 1,16 ; IC à 95 % : 1,09 à 1,24), l'abstinence après la période de suivi la plus longue. Toutes les études incluses, sauf deux, comportaient au moins quatre sessions de soutien. La plupart des essais étaient basés sur un traitement de substitution de la nicotine. Aucun effet significatif n'a été détecté dans les études utilisant la nortriptyline (deux essais) ou la varénicline (un essai), mais ceci reflète l'absence de données. Dans les analyses en sous-groupes, les études qui comportaient au moins quatre sessions de contact personnel dans le groupe d'intervention et aucun contact personnel dans le groupe de contrôle avaient des résultats légèrement supérieurs (six essais ; RR = 1,25 ; IC à 95 % : 1,08 à 1,45), tout comme les études où le groupe d'intervention recevait un soutien entièrement par téléphone (six essais ; RR = 1,28 ; IC à 95 % : 1,17 à 1,41). On a relevé des preuves moins fiables du bénéfice d'un soutien comportemental supplémentaire dans les essais où tous les participants, y compris ceux des groupes témoins, avaient au moins 30 minutes de contact personnel (18 essais ; RR = 1,11 ; IC à 95 % : 0,99 à 1,25). Aucune différence significative n'a été constatée entre les sous-groupes et les deux dernières analyses en sous-groupes n'étaient pas pré-spécifiées. Aucun essai n'a été considéré comme présentant un risque élevé de biais, dans aucun domaine.

Conclusions des auteurs

Le soutien comportemental, apporté en personne ou par téléphone, aux personnes utilisant une pharmacothérapie pour arrêter de fumer a un effet petit, mais important. Un soutien comportemental plus intensif augmente la probabilité de réussite d'environ 10 % à 25 %, d'après une estimation regroupant 38 essais. Une analyse en sous-groupes d'un plus petit nombre d'essais suggère que le bénéfice pourrait être légèrement supérieur lorsque la comparaison est établie entre un groupe témoin sans soutien et un groupe d'intervention comportementale bénéficiant d'au moins quatre sessions de contact. L'analyse en sous-groupe suggère également qu'il peut y avoir un bénéfice accru légèrement inférieur lorsque les personnes reçoivent un soutien encore plus intensif par le biais de sessions plus nombreuses ou plus longues, en plus du contact personnel.

Plain language summary

Does more support increase success amongst people using medications to quit smoking?

Medications (including all types of nicotine replacement therapy, bupropion and varenicline) have been shown to help people quit smoking. It has been unclear how much additional benefit is gained from also providing behavioural support, such as counselling or a telephone quitline. Combined results from 38 trials suggests that increasing the amount of behavioural support (in person or via telephone) increases the chances of quitting smoking for the long term by about 10 to 25%. The effect may be a little greater when adding some support compared to no support, and a little smaller when more support is compared to some support. Providing some personal contact is beneficial, and people making a quit attempt with pharmacotherapy will increase their chances of success of they also have access to behavioural support.

Résumé simplifié

Un soutien accru améliore-t-il le taux de réussite chez les personnes utilisant des médicaments pour arrêter de fumer ?

Il est prouvé que certains médicaments (dont tous les types de traitements de substitution de la nicotine, le bupropion et la varénicline) aident les gens à arrêter de fumer. On est toutefois moins certain du bénéfice supplémentaire que procure le soutien comportemental, tel que les services de conseil en personne ou par téléphone. Les résultats combinés de 38 essais suggèrent qu'un soutien comportemental accru (en personne ou par téléphone) augmente les chances de sevrage tabagique à long terme d'environ 10 à 25 %. Le résultat peut être légèrement supérieur pour les patients qui bénéficient d'un soutien ordinaire par rapport à ceux qui ne bénéficient d'aucun soutien, et légèrement inférieur pour les patients qui bénéficient d'un soutien plus intensif par rapport à ceux qui bénéficient d'un soutien ordinaire. Le contact personnel est bénéfique et les personnes qui essaient d'arrêter de fumer à l'aide de la pharmacothérapie augmenteront leurs chances de réussite avec un soutien comportemental.

Notes de traduction

Traduit par: French Cochrane Centre 5th March, 2013
Traduction financée par: Minist�re Fran�ais des Affaires sociales et de la Sant�

Summary of findings(Explanation)

Summary of findings for the main comparison. Behavioural interventions as adjuncts to pharmacotherapy for smoking cessation
  1. 1 All studies rated at low or unclear risk of bias
    2 No overall evidence of statistical heterogeneity (I² = 3%), or of differences between the subgroups defined by pharmacotherapy

Behavioural interventions as adjuncts to pharmacotherapy for smoking cessation
Patient or population: People using smoking cessation pharmacotherapy
Settings: Health care and community settings
Intervention: Behavioural interventions as adjuncts to pharmacotherapy
OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments
Assumed riskCorresponding risk
ControlBehavioural interventions as adjuncts to pharmacotherapy
Smoking cessation at longest follow-up
Follow-up: 6 - 24 months
Study populationRR 1.16
(1.09 to 1.24)
15506
(38 studies)
⊕⊕⊕⊕
high 1,2
 
183 per 1000213 per 1000
(200 to 227)
Median quit rate
210 per 1000244 per 1000
(229 to 260)
*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

Giving up smoking is the most effective way for people who smoke to reduce their risk of premature death and disability. People who smoke need to quit as soon as possible by using the evidence-based aids that increase their chances of success. These aids include behavioural support and pharmacotherapies. Behavioural support interventions range from written materials containing advice on quitting to multisession group therapy programmes or repeated individual counselling in person or by telephone. Providing standard self-help materials alone seems to have at best a small effect on success, but there is good evidence of a benefit of individually tailored self-help materials or more intensive advice or counselling (Lancaster 2005a; Lancaster 2005b). There is also good evidence that nicotine replacement therapy products (NRT), varenicline, bupropion and nortriptyline all increase the long term success of quit attempts (Cahill 2012; Hughes 2007; Stead 2012b). Clinical practice guidelines recommend that health care providers offer people who are prepared to make a quit attempt both pharmacotherapy and behavioural support. The two types of treatment are believed to have complementary modes of action, and to independently improve the chances of maintaining long term abstinence (Hughes 1995; Cofta-Woerpel 2007). Although guidelines recommend intensive support to improve abstinence rates, it is also recognised that many people will not attend multiple sessions. NRT products are available over the counter without a prescription in many countries, and people who purchase them may not access any specific behavioural support. People who obtain prescriptions for pharmacotherapies are more likely to receive some support, but this may be focused on explaining proper use of the drug and not on counselling.

Other Cochrane Tobacco Addiction reviews have evaluated the evidence on behavioural and pharmaceutical interventions individually. These reviews restrict inclusion to trials where interventions are unconfounded. Trials of pharmacotherapies must provide the same amount of behavioural support (materials, advice, counselling contacts) to all participants whether they receive active treatment, or a placebo or no medication. Likewise, when behavioural interventions are evaluated there should be no systematic difference in the offer of medications between the active and control arms of the trial. Only reviews that evaluate interventions by specific providers (e.g. nurses, Rice 2008), or in specific settings (e.g. hospitals, Rigotti 2012), may include trials of interventions that combine behavioural therapies and various medications (e.g. NRT, bupropion, varenicline).

This review is one of two that systematically identify trials of interventions that combine effective pharmacotherapies (NRT, varenicline, bupropion, nortriptyline) with behavioural support (tailored materials, brief advice, in person or telephone counselling). This review evaluates trials that compare different levels of behavioural intervention for people receiving any pharmacotherapy for smoking cessation, to provide an estimate of the effectiveness of intensifying behavioural support as an adjunct to pharmacotherapy. The companion review (Stead 2012a) includes trials in which an intervention combining pharmacotherapy and behavioural support is compared to standard care or a brief behavioural intervention without pharmacotherapy.

Objectives

To evaluate the effect of increasing the intensity of behavioural support for people using smoking cessation medications.

Methods

Criteria for considering studies for this review

Types of studies

Randomized or quasi-randomized controlled trials.

Types of participants

We included trials that recruited people who smoke in any setting, with the exception of trials which only recruited pregnant women or adolescents. These populations are considered in specific reviews (Grimshaw 2006; Coleman 2012). Trial participants did not need to be selected according to their interest in quitting, or their suitability for pharmacotherapy, but since pharmacotherapy was offered or provided, participants were expected to be relatively motivated and prepared to use medication as part of their quit attempt.

Types of interventions

We included trials of smoking cessation interventions where all participants had access to a smoking cessation pharmacotherapy (including NRT, varenicline, bupropion and nortriptyline, or a combination or choice of these) and in which one or more intervention conditions received more intensive behavioural support than the control condition. Control group participants could be offered any level of support from minimal (e.g. written information provided as part of the medication prescription) to multisession counselling, but support must have been of a lower intensity (based on number or length of sessions) than that given to intervention participants. We did not include trials testing specific behavioural components that used a control matched for contract frequency and duration.

Types of outcome measures

Following the standard methodology of the Tobacco Addiction Group the primary outcome was smoking cessation at the longest follow-up using the strictest definition of abstinence, i.e. preferring sustained over point prevalence abstinence and using biochemically validated rates where available. In addition we noted any other abstinence outcomes reported and conducted sensitivity analyses if the choice of outcome in a study might have altered the results of a meta-analysis. We will exclude trials reporting less than six months follow-up from the start of intervention. 

Search methods for identification of studies

We identified trials from the Cochrane Tobacco Addiction Specialised Register (the Register). This is generated from regular searches of The Cochrane Library, MEDLINE, EMBASE, PsycINFO and Science Citation Index for trials of smoking cessation or prevention interventions. The most recent search of the Register was in July 2012. At the time of the search the Register included the results of searches of the Cochrane Central Register of Controlled trials (CENTRAL), issue 7, 2012; MEDLINE (via OVID) from 1946 to update 20120622; EMBASE (via OVID) from 1974 to week 201227 and PsycINFO (via OVID) from 1967 to update 20120625. See the Tobacco Addiction Group Module in the Cochrane Library for full search strategies and a list of other resources searched.

We used the same search strategy that we used in the companion review that compared interventions that combined pharmacotherapy and behavioural therapy with controls that offered neither (Stead 2012a). Records were screened for relevance to either review. We searched the Register for records with any mention of pharmacotherapy including any type of NRT, bupropion, nortriptyline or varenicline in title, abstract or indexing terms (see Appendix 1 for the final search strategy). We checked titles and abstracts to identify trials of interventions for smoking cessation that combined pharmacotherapy with behavioural support. We also checked the excluded study lists of reviews of behavioural therapies and pharmacotherapy for trials excluded because pharmacotherapy was confounded with additional behavioural support compared to the control group. Trials with a factorial design that varied both pharmacotherapy and behavioural conditions were also considered for inclusion. We also tested an additional MEDLINE search using the smoking related terms and design limits used in the standard Register search and the MeSH terms ‘combined modality therapy’ or (Drug Therapy and (exp Behavior therapy or exp Counseling)). This search retrieved a subset of records already screened for the inclusion in the Register and was used to assess whether it might retrieve studies where there was no mention of a specific cessation pharmacotherapy in the title, abstract or indexing. We did not find any additional studies from this approach.

Data collection and analysis

Selection of studies

LS (who is also the Trial Search Co-ordinator for the Cochrane Tobacco Addiction Group) identified potentially relevant trials according to the criteria above and obtained the full text of papers reporting primary outcomes of all potentially relevant trials. Where there was uncertainty about inclusion or exclusion, trials were discussed with TL.

Data extraction and management

LS extracted data and categorised trials for subgroup analysis, with data extraction checked by TL. The following information was extracted:

  • Country and setting of trial

  • Method of recruitment, including any selection by motivation to quit

  • Method of sequence generation

  • Method of allocation concealment

  • Characteristics of participants including gender, age, smoking rate

  • Characteristics of intervention deliverer

  • Common components: type, dose and duration of pharmacotherapy

  • Intervention components: type and duration of behavioural support

  • Control group components: type and duration of behavioural support

  • Outcomes: primary outcome length of follow-up and definition of abstinence, other follow-ups and abstinence definitions, use of biochemical validation.

Assessment of risk of bias in included studies

Studies were evaluated on the basis of the randomization procedure, allocation concealment, incomplete outcome data assessment and any other bias (Cochrane Handbook 2011; Schulz 2002a; Schulz 2002b).

Measures of treatment effect

Trial effects were expressed as a relative risk calculated as: (quitters in treatment group/total randomized to treatment group)/(quitters in control group/total randomized to control group). A relative risk greater than 1 indicates a better outcome in the intervention group than in the control condition.

Dealing with missing data

Numbers lost to follow-up were reported by group in the risk of bias table. Following standard Cochrane Tobacco Addiction Group methods, people lost to follow-up were assumed to be smoking and were included in the denominators for calculating the relative risk. Any exceptions to this assumption were reported in the risk of bias table. Any deaths during follow-up were noted separately and excluded from denominators.

Assessment of heterogeneity

We considered pooling all trials comparing more and less intensive behavioural support if statistical heterogeneity as assessed by the I² statistic (Higgins 2003) was less than 50%.

Data synthesis

For groups of trials where meta-analysis was judged appropriate, relative risks were pooled using a Mantel-Haenszel fixed-effect model, and a pooled estimate with 95% confidence intervals was reported.

If trials had more than one intervention condition we compared the most intensive combination of behavioural support and pharmacotherapy to the control in the main analysis.

We categorise the intensity of behavioural support in both intervention and control conditions based on two of the categories used in the US Guidelines (Fiore 2008): ‘Total amount of contact time’ (Categories: 0, 1 to 30*, 31 to 90, 91 to 300, > 300 minutes [*guideline categories 1 to 3 and 4-30 combined]) and ‘Number of person-to-person sessions’ (Categories: 0*, 1 to 3*, 4 to 8, > 8 [*guideline used 0 to 1, 2 to 3]).

Subgroup analysis and investigation of heterogeneity

We used the difference in intensity of support (number or duration of contacts) between intervention and control conditions as the main potential feature to explain any heterogeneity. We expected trials testing larger differences in intensity (that is, using longer, more frequent sessions in the intervention condition and brief or no contact in the control) to show larger treatment effects. We also considered whether the definition and duration of follow-up, or the use of biochemical validation of cessation, had any impact on treatment effect.

Sensitivity analysis

Had we judged any trials to be at high risk of bias in any domain, we would have considered whether the results were sensitive to their exclusion.

Results

Description of studies

See: Characteristics of included studies; Characteristics of excluded studies; Characteristics of ongoing studies.

Results of the search

The Register search retrieved approximately 2200 records. Most records were excluded as not relevant based on title and abstract. Of the records that did relate to trials of interventions for smoking cessation most were not relevant because they were placebo-controlled trials of pharmacotherapies, in which the behavioural support was the same for intervention and control conditions. Eighty-three studies (130 records) were identified for inclusion or listed as excluded. Fifty-five further studies that did not offer pharmacotherapy to the control group were included in Stead 2012a. Six studies had multiple study arms and contributed to both Stead 2012a as well as to this review. All reports related to a study are listed in the reference section with the primary report used for data extraction identified. Study identifiers are based on the first author and year of publication of the main study report.

Included studies

We identified 38 studies as relevant for inclusion. Over 15,000 participants were included in relevant arms of these studies. Details of each study are given in the Characteristics of included studies table.

Study setting, participant recruitment and motivation

Eleven studies recruited people in a health care setting (excluding smoking cessation clinics); this included four studies in primary care (Ockene 1991, Fiore 2004; Aveyard 2007; Ellerbeck 2009), one in a chest clinic (Tonnesen 2006), one in a cardiovascular disease outpatient clinic (Wiggers 2006), one in HIV clinics (Lloyd-Richardson 2009), one in mental health clinics (Williams 2010), two in substance abuse clinics (Lifrak 1997; Stein 2006) and one in a Veterans Administration hospital (Simon 2003). Since the intervention included the provision of pharmacotherapy, almost all of the studies recruiting in a health care setting recruited volunteers who were interested in making a quit attempt, though Wiggers 2006 used a motivational interviewing approach and participants did not all make quit attempts. Ockene 1991 offered nicotine replacement therapy (NRT) so participants were not initially selected by motivation, and Ellerbeck 2009 included a small proportion of people in the pre-contemplation stage. A further four studies recruited members of health maintenance organisations (HMOs) (Lando 1997; Swan 2003; Boyle 2007; Swan 2010). Boyle 2007 proactively recruited HMO members who had filled a prescription for smoking cessation medication, the others sought volunteers by advertising to HMO members. The remaining 23 studies recruited community volunteers interested in quitting, including two which recruited people who were attending cessation clinics (Alterman 2001; Rovina 2009).

Intervention and control conditions

NRT was offered in the majority of studies, with 19 providing nicotine patch only. Most of these provided a supply for up to 12 weeks, but one study offered only a two week supply (MacLeod 2003). Six studies used nicotine gum, one used sublingual tablets, and one did not specify type (Bushnell 1997). Three studies provided bupropion alone (Swan 2003; McCarthy 2008; Rovina 2009), one provided nortriptyline alone (Hall 1998) and one provided varenicline alone (Swan 2010). In two studies, participants could use either NRT or bupropion (Boyle 2007; Ellerbeck 2009). Gariti 2009 randomised participants to NRT or bupropion using a double dummy design. Hall 2002 randomised participants to either bupropion or nortriptyline (placebo arms not used in this review). Two studies provided combination therapy of both NRT and bupropion (Killen 2008; Hall 2009).

The intensity of the behavioural support was very varied for both intervention and control groups. In six trials there was no personal contact for the controls: in five, participants received pharmacotherapy by mail (Solomon 2000; Solomon 2005; MacLeod 2003; Boyle 2007; Ellerbeck 2009) and in Fiore 2004 there was no counselling or advice for the control group although there was face-to-face contact with study staff. In 16 studies, the control arms had between one and three contacts (which could be face-to-face or by telephone) and most of these had a total contact duration of between four and 30 minutes. Fourteen studies scheduled four to eight contacts for the controls, and these most typically had a total contact time of 91-300 minutes.

Typically, the intervention involved only a little more contact than the control, so that the least intensive control conditions occurred in trials with only moderate intensity interventions. In Analysis 1.2, we grouped trials by number of intervention and control contacts. The number of contacts planned was not always delivered, but generally using the average number delivered would not have changed the coding category. In a few cases where the number of contacts was either not specified or open-ended we coded the average number delivered. In nine trials, the intervention and control condition fell into the same coding category for number of contacts (Bushnell 1997; Huber 2003; Stein 2006; Tonnesen 2006; Wiggers 2006; Aveyard 2007; McCarthy 2008; Wu 2009; Williams 2010). The planned duration of intervention sessions was very variable, from 10-15 minutes to two hours, but 12 of the trials planned to provide between 91 and 300 minutes of contact and 16 offered more than 5 hours of support. A summary of the number of sessions and duration for intervention and control conditions for each trial is provided in Appendix 2.

Length of follow-up and definitions of abstinence

Most studies followed participants for a year from the target quit date, or entry into the study. Exceptions were Hall 2009 and Ellerbeck 2009 which each had a two-year follow-up. The design of the Ellerbeck study, in which participants were repeatedly offered support to quit, means that participants who were quit at the end of follow-up would not necessarily have been quit for as long as two years. Seven studies only followed participants for six months (Jorenby 1995; MacLeod 2003; Stein 2006; Bushnell 1997; Lloyd-Richardson 2009; Wu 2009; Swan 2010).

The majority of studies reported abstinence as a prevalence measure, rather than requiring reported sustained abstinence, or abstinence at multiple follow-up points. Eight studies did not attempt any biochemical verification of self-reported abstinence (Ockene 1991; MacLeod 2003; Swan 2003; Solomon 2005; Otero 2006; Boyle 2007; Hollis 2007; Swan 2010). Only one of these studies (Otero 2006) included face-to-face contact between study staff and participants; all the others involved only telephone contact, so validation was not felt to be feasible.

Excluded studies

We list 48 studies as excluded, the majority of which were excluded because they provided less than six months follow-up or because both arms received the same duration and length of behavioural support. Studies in which the intervention group received both pharmacotherapy and behavioural support and the control group received neither (or just brief behavioural support) were eligible for the companion review and are included or excluded there (Stead 2012a). We excluded three studies where the additional behavioural support did not include any person-to-person contact. One of these involved automated telephone calls (Velicer 2006) and one provided access to an internet site (Japuntich 2006). We also excluded one study that had the same number of contacts and contact duration (Ahluwalia 2006). A full list of excluded studies along with reasons for their exclusion can be found in the Characteristics of excluded studies table.

Risk of bias in included studies

Allocation

Eleven studies were either judged to be at low risk of bias based on the reported method of random sequence generation and allocation concealment. The remaining studies did not given enough detail on one or both of these aspects so the risk of bias was judged to be unclear.

Blinding

We did not formally assign a risk of performance bias to each trial. Because of the nature of the intervention, people providing the behavioural support could not be blind. The varying designs of the studies means that some providers of care would have had contact with all conditions whilst some would only have had contact with intervention condition participants. Some care providers would have been providing the same support for all trial participants, some would have been providing more intensive support to one or more intervention groups, and in some cases the treatment was highly individualised. Whilst performance bias cannot be ruled out we do not think it is a major threat to the validity of this group of trials or that individual trials can be identified as being at higher risk than others in this domain.

Ideally all follow-up data would be collected by people who remained blind to participant status. Only a few trials reported this explicitly, but others described standardised methods for follow-up and attempts to contact non-responders which would reduce detection bias. The use of biochemical validation would also reduce the risk of detection bias; the impact of biochemical validation is assessed in subgroup analysis.

Incomplete outcome data

Loss to follow-up is often relatively high in smoking cessation trials. If trials lost less than 20% of participants at longest follow-up we judged the risk of bias to be low in this domain. In most of the included trials, the proportion lost to follow-up was more than 20% but losses were balanced across groups and less than 40%; for these we also classified the risk of bias as low. Two studies which reported overall losses to follow-up of greater than 20% but did not provide a breakdown by treatment arm were rated at unclear risk of bias (Bushnell 1997; Tonnesen 2006), as were a further three studies that did not report level of attrition (Hall 1994; Otero 2006; Smith 2001).

Other potential sources of bias

No studies were judged to be at risk of other potential sources of bias.

Effects of interventions

See: Summary of findings for the main comparison Behavioural interventions as adjuncts to pharmacotherapy for smoking cessation

There was no overall evidence of statistical heterogeneity (I² = 3%) or of differences between the subgroups defined by pharmacotherapy, so we pooled all 38 studies, including a total of over 15,000 participants. Hall 2002 contributes separate data to two subgroups in the primary meta-analysis. Twelve of the studies had point estimates below 1, that is, with higher quit rates in the less intensive condition, but all these had wide confidence intervals (CI). Only five studies detected benefits of intervention with confidence intervals that excluded 1. The estimated risk ratio (RR) was 1.16, with 95% CI 1.09 to 1.24. This suggests that increasing the intensity of behavioural support for people making a cessation attempt with the aid of pharmacotherapy typically leads to a relatively small increase in the proportion who are quit at 6 to 12 months (Figure 1, Analysis 1.1, Summary of findings for the main comparison).

Figure 1.

Effect of increasing behavioural support. Abstinence at longest follow-up.

Subgroups by type of pharmacotherapy

The effect size was similar and also reached statistical significance in the subgroups using NRT (27 trials, RR 1.15, 95% CI 1.06 to 1.25 ); bupropion (four trials, RR 1.25 95% CI 1.08 to 1.44). Subgroup results were not significant for nortriptyline (two trials, RR 0.98, 95% CI 0.59 to 1.63), varenicline (one trial, RR 1.11, 95% CI 0.89 to 1.37), NRT and bupropion combined (two trials, RR 1.22, 95% CI 0.98 to 1.52) or a choice of pharmacotherapy (three trials, RR 1.15, 95% CI 0.92 to 1.45). This is likely to reflect the smaller number of studies and lower precision rather than a true difference in effect. A test for differences between subgroups was not significant (p = 0.87).

Subgroups by difference in intensity

Analysis 1.2 categorises trials based on number of contacts, with the subgroups with the largest contrast in intensities listed first and studies where the intensity of intervention and control fell into the same category shown last. There was little evidence of any dose-response but the point estimate was highest for the subgroup in which controls did not have any personal contact (six trials, RR 1.25, 95% CI 1.08 to 1.45). All interventions in this subgroup of trials involved at least four contacts. Since there was little heterogeneity overall it was not surprising that subgroups did not consistently reduce heterogeneity. We did not repeat this approach for duration of intervention categories as inspection suggested that the number of studies falling into different categories was small and that further subgroup analysis could be misleading.

At the suggestion of a peer reviewer we did two additional subgroup analyses. In Analysis 1.3 we categorised only by control group contact to investigate whether there was a difference between trials where the control could be categorised as a brief intervention (either no contact or up to 30 minutes) and trials which might be characterised as testing a dose-response for behavioural support, which we defined as being where the controls received more than 30 minutes of behavioural support. Twenty trials and about two thirds of the participants came in the first subgroup, and the estimate remained very close to the main analysis (RR 1.18, 95% CI 1.10 to 1.27). There were 18 trials in the 'dose-response' category; the point estimate was smaller and the confidence intervals included 1 (RR 1.11, 95% CI 0.99 to 1.25). This was not sensitive to excluding studies where the intervention and control fell into the same intensity category. In Analysis 1.4, we categorised studies according to whether there was some face-to-face contact as part of the intervention, or whether all support was given by telephone. In the subgroup of six studies using telephone counselling (which had some overlap with studies where there was no personal contact for the control), the point estimate was higher although the CIs were wide (RR 1.28, 95% CI 1.17 to 1.41). In the subgroup of 29 studies where both intervention and control conditions had face-to-face support, there was no evidence of benefit but the upper CI was still consistent with a possible small benefit (RR 1.09, 95% CI 0.99 to 1.19).

Sensitivity analyses

Inclusion of medium intensity intervention from studies with multiple intervention conditions

Seven studies (Jorenby 1995; Alterman 2001; Smith 2001; Fiore 2004; Hollis 2007; Ellerbeck 2009; Swan 2010) included an intervention condition intermediate in intensity between the highest intensity and the control. These arms were not included in the primary analysis in case they reduced the contrast between intervention and control. In a sensitivity analysis we added in these arms. This had almost no impact on the estimated effect (RR 1.15, 95% CI 1.08 to 1.22, Analysis 2.1), tending to support the finding that there is not a clear dose-response relationship with amount of support.

Definition of abstinence & use of validation

We considered whether the way in which abstinence was defined was related to the effect size, and also to absolute quit rates. We did not find any difference in relative effect between studies that reported point prevalence rather than sustained abstinence at 12 months (Analysis 2.2). Some studies that reported sustained outcomes also reported point prevalence rates, but substituting the less stringent definition did not change the overall findings. However, studies with point prevalence outcomes had, on average, higher quit rates in both intervention and control arms. A study comparing outcomes based on different abstinence definitions reported within studies found that, for pharmacotherapy studies, point prevalence and sustained abstinence outcomes were strongly related, with sustained abstinence averaging around 74% of point prevalence rates (Hughes 2010). In this review there was a bigger difference, and the average quit rate in studies that reported a sustained outcome was 50 to 60% of the average for studies reporting point prevalence.

Most of the studies used biochemical validation of self-reported cessation. When we excluded the six studies that did not, the estimated effect fell slightly and the confidence intervals no longer excluded 1 (RR 1.09, 95% CI 0.99 to 1.21), whilst the effect in the excluded subgroup without validation supported a benefit (RR 1.23, 95% CI 1.12 to 1.34). The importance of this is unclear; whilst it is possible that the absence of validation was a source of bias, it is also possible that these studies had genuinely larger effects; five involved telephone counselling, and two had no personal contact in the control, potentially leading to a larger contrast between intervention and control conditions.

Discussion

Summary of main results

A meta-analysis pooling 38 studies with a total of over 15,000 participants suggests that providing more intense behavioural support for people making a cessation attempt with the aid of pharmacotherapy will increase the success rates by about 16%. There was little evidence of statistical heterogeneity overall despite the variability in the amount and nature of the behavioural support tested. Sensitivity analyses suggest that this estimate is quite robust. Although the relative effect is small, it is important to put the effect in the context of control conditions that were offering effective pharmacotherapy and, typically, some behavioural support, i.e. a level of support consistent with guideline best practice. Quit rates in the control groups reflected this, with a median quit rate across trials of 21% (interquartile range 14 to 26%). So the estimated relative increase translates into an absolute increase of around two to four percentage points. Given the importance of smoking cessation for future health outcomes this is a clinically relevant difference (West 2007).

There were potentially important differences between trials in the relative difference in the support given to the intervention and control groups. Despite the lack of statistical heterogeneity we undertook a number of subgroup analyses including some that were not prespecified. In response to a concern that we were combining tests of behavioural support versus no support with tests of a dose-response to intensity of support we divided trials into those where the control was a brief intervention, operationalised as under 30 minutes contact but also including written support only, and those where the control condition was more intensive. There was no longer a significant effect in the dose-response subgroup, but it should be stressed that this was an exploratory analysis. It does, however, suggest that the dose-response curve is shallow for behavioural support. We drew similar conclusions in a companion review to this, which compared combined pharmacotherapy and behavioural support to minimal support; indirect comparisons between trials of more and less intensive interventions also failed to detect large differences (Stead 2012a). The present review also detected a clearer benefit of more support in studies where all contact was delivered by telephone, but this too was not prespecified and may reflect the larger size of trials done in quitline settings, or possibly that most of these studies did not use biochemical validation of abstinence.

One explanation for the relatively small impact of providing more behavioural support is that it is not provided at the time when it could be most effective. Relapse after initial success is the norm for quit attempts, and by the time people are getting additional calls they may already have relapsed. Various study authors commented on this (e.g. Reid 1999; Smith 2001). Although these studies are not typically characterised as being about 'relapse prevention' there is a small overlap between this review and the Cochrane review of relapse prevention interventions (Hajek 2009), which concluded that there was no evidence of a benefit of additional behavioural support to prevent relapse. On the other hand, in some cases an initial benefit of the intervention disappeared once treatment ended, and authors suggested that further extended support might have made a difference (e.g. Solomon 2000; Killen 2008), although replication of one of these studies with more extended support (Solomon 2005) still showed the same pattern of late relapse. We did not include two studies by Hall and colleagues which tested behavioural support and pharmacotherapy extended for a year from quit date in a factorial design (Hall 2004; Hall 2011). Including the these studies would not have affected the findings.

A potential limitation of the review is that we focused on the amount of behavioural support rather than the specific components, or the quality of delivery. If shorter interventions happened to include more effective components, an impact of more intensive interventions could be obscured. However, there is little evidence about the effect of specific components beyond the intratreatment social support common to all these interventions. Michie and West have developed a taxonomy of behaviour change techniques (Michie 2011) and also shown a significant association between the use of some of these techniques and short term outcomes in the English Stop Smoking Services (West 2010). The size of associations with individual techniques was relatively small. Given the large number of potential techniques, and rather small range of effect sizes in the trials in the review, we think it unlikely that any single technique, or group of techniques, could be identified that would critically affect outcomes.

Overall completeness and applicability of evidence

The studies identified for this review have all been conducted in the USA or Europe. It is possible that we have failed to find relevant studies conducted in other places. Participants were typically moderate to heavy smokers and were interested in quitting. Most studies recruited participants who had already tried to quit a number of times. One exception was Wu 2009, which recruited Chinese Americans, many of whom did not report previous quit attempts. This study showed one of the largest effect sizes, suggesting that the additional behavioural support could be at least as effective for people who have not already tried many times. It is possible that the explanation for the relatively small effect of the behavioural adjunct overall was that many participants in the trials were already familiar with the approaches being used.

Quality of the evidence

We did not identify any trials as being at high risk of bias in any domain. The quality of the trials was typical of smoking cessation research in general. We did not formally evaluate whether there was a risk of performance bias due to lack of blinding of providers or participants. Blinding of providers would not have been possible, and it was difficult to determine whether participants knew how their treatment compared to the other options offered. All participants were getting an active pharmacotherapy and would have been aware of this (apart from a small proportion in placebo controlled factorial studies). Expectancy effects for the behavioural components would probably have been small, and we do not think the small effect of the interventions could be attributed entirely to higher expectancies in intervention conditions.

The absence of biochemical validation of self-reported abstinence in some studies does complicate the interpretation of the results since a sensitivity analysis excluding them did widen the confidence intervals and increase the possibility that the intervention had no effect. A requirement for validation will almost always reduce the absolute success rates, but absence of validation will only lead to an overestimate of effects if intervention participants are more likely to misreport abstinence. All trial participants were receiving an active treatment but some of the trials without validation had control groups with no personal contact, whilst intervention groups had telephone contact (seven trials) or face-to-face contact (one trial). It is theoretically possible that this could make people in the intervention condition more liable to misreport their status. It is generally considered that biochemical validation is not needed in adult population studies if there is no face-to-face contact. In these settings it is argued that the proportion of people misreporting abstinence is low and similar for intervention and control conditions, whilst difficulties in collecting samples by post may lead to underestimates of quitting success (Hollis 2007).

A funnel plot (not shown) did not suggest the presence of publication bias. Given the large number of included studies and the degree of homogeneity between them, it is unlikely that smaller unpublished studies with less significant findings, if they existed, would significantly alter our results.

Potential biases in the review process

We used the Cochrane Tobacco Addiction Specialised Register to identify studies. The Register includes reports of trials identified from the major bibliographic databases. There is no straightforward term for the type of intervention we were interested in but we screened any trial report that mentioned a pharmacotherapy. It is possible that the Register does not include all relevant trial reports or that we failed to identify some. Our methods for data extraction and analysis are those used for other Cochrane reviews. The practice of imputing missing data as smoking is standard practice for primary and secondary research in smoking cessation and has the advantage that absolute cessation rates are not inflated by ignoring loss to follow-up. Bias in the relative effect will only be introduced if misclassification differs for people who are lost from the intervention condition compared to the control. If proportionately more of those who are lost in the control group are assumed to be smokers but have in fact quit then the treatment effect would be overestimated.

Agreements and disagreements with other studies or reviews

The major source of systematic data about the dose-response to behavioural support is the US Public Heath Service Clinical Practice Guideline, last updated in 2008 (Fiore 2008). This includes meta-analyses (last updated in 2000) for different levels of support and contact time. The analyses included trials of different levels of support versus control. These showed trends towards increasing effects in trials that had more sessions and more contact time, compared to minimal conditions. For example, estimated effects compared to minimal contact differed between trials with four to 30 minutes of contact time (OR 1.9, 95% CI 1.5 to 2.3) and trials with 91 to 300 minutes (OR 3.2, 95% CI 2.3 to 4.6) (Fiore 2008 Table 6.9) and between two to three treatment sessions (OR 1.4, 95% CI 1.1 to 1.7) and over eight sessions (OR 2.3, 95% CI 2.1 to 3.0) compared to 0-1 sessions (Fiore 2008 Table 6.10). These analyses are not limited to direct (within trial) comparisons of treatment intensity. They also do not distinguish between studies with and without pharmacotherapy, and the majority of studies in our analysis were published after 2000 so would not have been included. Our review is likely to give a more precise estimate of the effect of additional support alongside pharmacotherapy based on the analysis of trials directly comparing different levels of support.

There is observational evidence that access to more behavioural support is associated with greater success in quitting. For example a study of English Stop Smoking Services, in which there is a high use of pharmacotherapy, found a positive association between the number of scheduled sessions and short-term quit rates (West 2010). A study of NRT users calling the California quitline found that people who received multiple sessions of counselling had higher quit rates after one year (Zhu 2000).

Authors' conclusions

Implications for practice

Providing behavioural support for smokers using established medication in an attempt to stop smoking will increase the proportion of successful attempts. More intensive behavioural support is likely to provide some additional benefit. This effect may be small in absolute terms but worthwhile given the considerable health gains from stopping smoking.

Implications for research

Identifying the optimal amount of behavioural support to use alongside pharmacotherapy remains a challenge. Studies need to be appropriately powered for small treatment effects, and test interventions that are acceptable and accessible to smokers, and affordable to deliver.

Acknowledgements

With thanks to Jamie Hartmann-Boyce for assistance with Risk of Bias and Summary of Findings tables, and the other editors of the Tobacco Addiction group for comments and suggestions on the draft.

Data and analyses

Download statistical data

Comparison 1. Effect of increasing behavioural support. Abstinence at longest follow-up
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Subgroups by type of pharmacotherapy3815506Risk Ratio (M-H, Fixed, 95% CI)1.16 [1.09, 1.24]
1.1 NRT279772Risk Ratio (M-H, Fixed, 95% CI)1.15 [1.06, 1.25]
1.2 Bupropion41995Risk Ratio (M-H, Fixed, 95% CI)1.25 [1.08, 1.44]
1.3 Nortriptyline2172Risk Ratio (M-H, Fixed, 95% CI)0.98 [0.59, 1.63]
1.4 Varenicline1800Risk Ratio (M-H, Fixed, 95% CI)1.11 [0.89, 1.37]
1.5 NRT & bupropion2690Risk Ratio (M-H, Fixed, 95% CI)1.22 [0.98, 1.52]
1.6 Choice of pharmacotherapy32077Risk Ratio (M-H, Fixed, 95% CI)1.15 [0.92, 1.45]
2 Subgroups by contrast in number of contacts between intervention & control3815506Risk Ratio (M-H, Fixed, 95% CI)1.16 [1.09, 1.24]
2.1 4 to 8 or > 8 contacts versus no contact63762Risk Ratio (M-H, Fixed, 95% CI)1.25 [1.08, 1.45]
2.2 More than 8 contacts versus 1 to 3 contacts2609Risk Ratio (M-H, Fixed, 95% CI)0.88 [0.66, 1.18]
2.3 4 to 8 contacts versus 1 to 3 contacts126817Risk Ratio (M-H, Fixed, 95% CI)1.16 [1.07, 1.27]
2.4 More than 8 contacts versus 4-8 contacts91568Risk Ratio (M-H, Fixed, 95% CI)1.15 [0.98, 1.35]
2.5 Intervention & control in same contact category92750Risk Ratio (M-H, Fixed, 95% CI)1.17 [0.97, 1.41]
3 Subgroups by duration of contact in control condition (not prespecified)3815506Risk Ratio (M-H, Fixed, 95% CI)1.16 [1.09, 1.24]
3.1 'Brief intervention' for control2011042Risk Ratio (M-H, Fixed, 95% CI)1.18 [1.10, 1.27]
3.2 'Dose response', over 30 minutes contact for control184464Risk Ratio (M-H, Fixed, 95% CI)1.11 [0.99, 1.25]
4 Subgroup by modality of contact (not prespecified)3815506Risk Ratio (M-H, Fixed, 95% CI)1.16 [1.09, 1.24]
4.1 All contact by telephone65311Risk Ratio (M-H, Fixed, 95% CI)1.28 [1.17, 1.41]
4.2 No contact for control group, face-to-face intervention32364Risk Ratio (M-H, Fixed, 95% CI)1.09 [0.88, 1.35]
4.3 Face-to-face contact for both intervention & control conditions297831Risk Ratio (M-H, Fixed, 95% CI)1.09 [0.99, 1.19]
5 Subgroups by setting3815506Risk Ratio (M-H, Fixed, 95% CI)1.16 [1.09, 1.24]
5.1 Recruited and treatment initiated in health care setting125422Risk Ratio (M-H, Fixed, 95% CI)1.09 [0.94, 1.26]
5.2 Members of health care organisation32833Risk Ratio (M-H, Fixed, 95% CI)1.21 [1.07, 1.37]
5.3 Community volunteers237251Risk Ratio (M-H, Fixed, 95% CI)1.17 [1.08, 1.27]
Analysis 1.1.

Comparison 1 Effect of increasing behavioural support. Abstinence at longest follow-up, Outcome 1 Subgroups by type of pharmacotherapy.

Analysis 1.2.

Comparison 1 Effect of increasing behavioural support. Abstinence at longest follow-up, Outcome 2 Subgroups by contrast in number of contacts between intervention & control.

Analysis 1.3.

Comparison 1 Effect of increasing behavioural support. Abstinence at longest follow-up, Outcome 3 Subgroups by duration of contact in control condition (not prespecified).

Analysis 1.4.

Comparison 1 Effect of increasing behavioural support. Abstinence at longest follow-up, Outcome 4 Subgroup by modality of contact (not prespecified).

Analysis 1.5.

Comparison 1 Effect of increasing behavioural support. Abstinence at longest follow-up, Outcome 5 Subgroups by setting.

Comparison 2. Sensitivity analyses
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Sensitivity analysis including intermediate intensity conditions. Adjunct behavioural support versus pharmacotherapy alone3817804Risk Ratio (M-H, Fixed, 95% CI)1.15 [1.08, 1.22]
1.1 NRT2711430Risk Ratio (M-H, Fixed, 95% CI)1.13 [1.04, 1.22]
1.2 Bupropion41995Risk Ratio (M-H, Fixed, 95% CI)1.25 [1.08, 1.44]
1.3 Nortriptyline2172Risk Ratio (M-H, Fixed, 95% CI)0.98 [0.59, 1.63]
1.4 Varenicline11202Risk Ratio (M-H, Fixed, 95% CI)1.11 [0.92, 1.34]
1.5 NRT & bupropion2690Risk Ratio (M-H, Fixed, 95% CI)1.22 [0.98, 1.52]
1.6 Choice of pharmacotherapy32315Risk Ratio (M-H, Fixed, 95% CI)1.15 [0.92, 1.43]
2 By outcome definition3815506Risk Ratio (M-H, Fixed, 95% CI)1.16 [1.09, 1.24]
2.1 12m validation PP outcomes only143202Risk Ratio (M-H, Fixed, 95% CI)1.01 [0.88, 1.15]
2.2 12m validated sustained outcomes72322Risk Ratio (M-H, Fixed, 95% CI)1.09 [0.87, 1.36]
2.3 Not 12m92783Risk Ratio (M-H, Fixed, 95% CI)1.21 [1.04, 1.40]
2.4 No validation at all87199Risk Ratio (M-H, Fixed, 95% CI)1.24 [1.14, 1.35]
Analysis 2.1.

Comparison 2 Sensitivity analyses, Outcome 1 Sensitivity analysis including intermediate intensity conditions. Adjunct behavioural support versus pharmacotherapy alone.

Analysis 2.2.

Comparison 2 Sensitivity analyses, Outcome 2 By outcome definition.

Appendices

Appendix 1. Register Search

Version of the search used in the Cochrane Register of Studies:

  1. NRT:TI,AB,KW    679

  2. (nicotine NEAR (replacement OR patch* OR transdermal OR gum OR lozenge* OR sublingual OR inhaler* OR inhalator* OR oral OR nasal OR spray)):TI,AB,KW      1796

  3. (bupropion OR zyban OR wellbutrin):TI,AB,KW,MH,EMT   546

  4. (varenicline OR champix OR chantix):TI,AB,KW,MH,EMT   278

  5. combined modality therapy:MH,KW    213

  6. ((behavio?r therapy) AND (drug therapy)):KW,MH,EMT,TI,AB    62

  7. ((counsel*) AND (*drug therapy)):KW,MH,EMT,TI,AB   185

  8. #1 OR #2 OR #3 OR #4 OR #5      2454

  9. #6 OR #7 OR #8    2509

  10. #9 AND INREGISTER 2200

Appendix 2. Summary of control and intervention characteristics

StudyControl Intervention Pharmacotherapy
 SessionsDurationSessionsDuration
 NumberCategoryTotalCategoryNumberCategoryTotalCategory
Fiore 20040000-354-815-25 min/sess91-300Nicotine patch
Boyle 20070000-3up to 9 (av 5 for acceptors)4-8est 10 min/sess31-90NRT or bupropion
MacLeod 20030000-354-860 mins total31-90Nicotine patch (2w)
Solomon 20000000-3up to 12, av 7>8average 9 min/sess31-90Nicotine patch
Solomon 20050000-3average 8 so target higher>8av 10 min/sess91-300Nicotine patch
Ellerbeck 20090000-364-8est 15-20 min/sess91-300NRT or bupropion
Hollis 200711-320 mins (mean)4-301 + up to 44-8average 47 or 60 tot31-90Nicotine patch
Jorenby 199511-3brief4-303 or 8 (not incl base)4-8? Or 1 hr ss>300Nicotine patch
Otero 200611-320 mins4-303-44-860 min/sess91-300Nicotine patch
Alterman 200111-330 mins4-301 + 3 + 12>8>300>300Nicotine patch
Rovina 200911-315 mins4-301 + 9>8>500>300Bupropion
Simon 200311-310 mins4-3064-8est 210 mins91-300Nicotine patch
Swan 200311-3brief4-3044-8'brief calls'31-90Bupropion
Swan 201011-35-10 mins4-3054-8av. tot 60 min31-90Varenicline
Wiggers 200611-3brief4-301 + 1-21-3est 60 mins31-90Nicotine patch
Stein 20061-21-3brief4-302-31-3est 60-90 mins31-90Nicotine patch
Lando 199711-390 mins incl 'orientation'31-901 + 44-810-15 min/sess91-300Nicotine patch
Ginsberg 199221-3est < 304-302+54-8est 30-60 mins91-300Nicotine gum
Lloyd-Richardson 200921-3est 304-3054-8120 mins + phone91-300Nicotine patch
Ockene 199121-310 + 5 mins4-302 + 34-815+3031-90Nicotine gum
Smith 200131-35-10 min/sess4-303 + 6>890 min/sess plus control>300Nicotine patch
Reid 199931-34531-903 + 34-845 + ?3031-90Nicotine patch
Gariti 200944-85-10 min/sess4-3010>810-15 *1091-300NRT or bup
Hall 200244-825-35 mins tot4-304 + 5>890 min/sess plus control>300Bup or Nort
Aveyard 200744-8˜80 mins31-9074-8˜14091-300Nicotine patch
Bushnell 199744-860 min/sess91-30084-860 min/sess>300NRT
Hall 198544-845 mins91-30014>875 min/sess>300Nicotine gum
Lifrak 199744-8est 30 min/sess91-3004 + 16>845 min/sess>300Nicotine patch
Wu 200944-860 min/sess (health education)91-30044-860 min/sess91-300Nicotine patch
Hall 198754-860 min/sess91-30014>875 min/sess>300Nicotine gum
Hall 200954-860 min/sess91-30011>820-40 min/sess>300Bupropion & gum
Hall 199454-890 min/sess>30010>8120 min/sess>300Nicotine gum
Hall 199854-890 min/sess>30010>8120 min/sess>300Nortriptyline
Huber 200354-845 min/sess>30054-890 min/sess plus control>300Nicotine gum
Tonnesen 200654-82.5 hrs91-30074-8210 + 5091-300Nicotine sublingual tablet
Killen 200864-830 min/sess91-3006 + 4>830 min/sess>300Bupropion & patch
Williams 20109>820 min/sess>30024>845 min/sess>300Nicotine patch
McCarthy 200813>8est 10 min/sess91-30013 incl 8 counselling>8extra 80 mins>300Bupropion

What's new

DateEventDescription
21 February 2013AmendedCorrection to 2 forest plot labels

Contributions of authors

LS developed the search strategy, screened search results and extracted data. TL agreed inclusion or exclusion of potentially relevant studies and checked data extraction. Both authors contributed to the text.

Declarations of interest

No conflicts of interest to report.

Sources of support

Internal sources

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

External sources

  • NHS National Institute for Health Research, UK.

Differences between protocol and review

Two additional subgroup analyses were added. We had initially planned to assess risk of bias based on blinding of participants and personnel, but given the nature of the studies provide a narrative discussion of this instead.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Alterman 2001

MethodsSetting: cessation clinic, USA
Recruitment: community volunteers
Participants240 smokers of > 1 pack/day; 45-54% F, av. age 40, av. cpd 27
Therapists: Nurse practitioners (NP) and trained counsellors
InterventionsPharmacotherapy: NRT; 21 mg patch for 8 wks (including weaning period)
1. Low intensity. Single 30 min session with NP.
2. Moderate intensity. as 1 plus additional 3 x 15-20 min sessions at wks 3, 6, 9 with NP.
3. High intensity. As 2. + 12 sessions cognitive behavioural therapy with trained therapist within 15 wks.
OutcomesAbstinence at 1 yr
Validation: urine cotinine < 50ng/ml, CO <= 9ppm
Notes3 versus 1 in main analysis. Quit rates significantly lower in 2 than 1 or 3. 35/160 quit when 2 & 3 combined
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk'Urn technique'
Allocation concealment (selection bias)Unclear riskNo details given. Allocation took place after baseline session common to all conditions.
Incomplete outcome data (attrition bias)
All outcomes
Low riskSmall and similar rate lost to follow-up in each group (approx 7%). ‘Intent to treat’ analyses reported in the paper exclude 2 deaths and 2 missing cotinine.

Aveyard 2007

MethodsSetting: 26 general practices (primary care clinics), UK
Recruitment: 92% volunteers in response to mailings
Participants925 smokers; 51% F, av. age 43, 50% smoked 11-20 cpd
Therapists: Practice nurses trained to provide cessation support & manage NRT
InterventionsPharmacotherapy: NRT; 16 mg patch for 8 wks
1. Basic support; 1 visit (20-40 mins) before quit attempt, phone call on TQD, visits/phone calls at 7-14 days & at 21-28 days (10-20 mins); 4 contacts, ˜80 mins
2. Weekly support; as 1. plus additional call at 10 days & visits at 14 & 21 days; 7 contacts, ˜140 mins
OutcomesAbstinence at 12m (sustained at 1, 4, 12, 26 wks)
Validation: CO <10ppm at treatment visits, saliva cotinine <15ng/ml at follow-ups
NotesTherapists were not full-time specialist counsellors. Difference between support conditions relatively small.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandom number generator
Allocation concealment (selection bias)Low riskNumbered sealed envelopes
Incomplete outcome data (attrition bias)
All outcomes
Low riskOver 30% lost to follow-up but similar percentage followed up in both groups (69% intervention vs 68% control, no evidence of differential attrition).

Boyle 2007

MethodsSetting: Health Maintenance Organization, USA
Recruitment: proactive recruitment of members filling a prescription for cessation medications (motivated)
Participants1329 HMO members; 58% F, av. age 47, 66% smoked >pack/day
InterventionsPharmacotherapy: All participants had filled a prescription. Almost 95% used; ˜51% only bupropion, 26% only NRT, remainder both
1. No further intervention
2. Proactive call to offer counselling, up to 9 calls, given choice of structured course or unstructured format
OutcomesAbstinence at 12m (repeated 7-day PP at 3m & 12m)
Validation: none
Notes49% of intervention group reached, 36% of those declined, 31% of total accepted counselling. Average no of calls 5. There was no evidence of a greater relative effect in those reached or those accepting counselling.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomized, stratified by presence of chronic disease. Method not described.
Allocation concealment (selection bias)Unclear riskNo details given
Incomplete outcome data (attrition bias)
All outcomes
Low riskOver 30% lost to follow-up but similar percentage followed up in both groups (66% intervention vs 65% control, no evidence of differential attrition).

Bushnell 1997

MethodsSetting: Community with large military population, USA
Recruitment: Community volunteers
Group size: max 50 American Cancer Society (ACS) or 15 Vanderbilt University Medical Center (VUMC)
Participants314 military and civilian smokers, excludes 198 people, assignment NS, who did not attend any sessions after randomization. 44% F, age and smoking not described
Therapists: ACS- trained volunteers, VUMC- healthcare professionals
InterventionsAll participants offered free NRT (in group 2 conditional on attending 75% classes)
1. ACS: 4 x 1 hr large group sessions (max 50), no TQD
2. VUMC: 8 x 1 hr group sessions (max 15), relapse prevention model including stress management, diet, exercise
OutcomesAbstinence at 6m (PP)
Validation: CO < 8 ppm, salivary cotinine ≤ 10 mg/ml
NotesEarly benefit of VUMC lost at 6 months. No observed effect in active duty participants at any time.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear risk'randomly assigned', method not stated, stratified by military or civilian
Allocation concealment (selection bias)Unclear riskNo details given
Incomplete outcome data (attrition bias)
All outcomes
Unclear risk198 (out of 512 randomized) did not participate, group not stated, not clear if subjects knew what group they were assigned to before attending first session

Ellerbeck 2009

MethodsSettng: Primary care patients, 50 rural practices, Kansas, USA
Recruitment: smoking patients not selected for motivation, but 67% of those eligible enrolled, only 8.7% in precontemplation stage of change
Participants750 smokers of >10 cpd, 59% F, av. age 47, av. cpd 24, 61% contemplation, 30% preparation
Interventions

All participants mailed an offer of free pharmacotherapy every 6 months, 4 times in total. Nicotine patch 21 mg for 6 wks or bupropion SR (150 mg twice daily) for 7 wks

1. Control. No other contact.

2. Moderate intensity disease management: up to 2 calls from counsellor in each cycle encouraging uptake of pharmacotherapy, newsletter mailings & periodic progress reports with counselling suggestions faxed to physician.

3. High intensity disease management, up to 6 calls at approx 1, 3, 6, 9, 12 wks from start of each

cycle.

Outcomes

Abstinence at 24m (PP). Study also reported analysis based on combination of effects at all follow-up points. Sustained abstinence not a suitable outcome since no quit date and repeated intervention.

Validation: attempted saliva cotinine (< 15 ng/ml) by mail at 12 & 24m. Proxy report used at 24m for non returners. Rate of validation similar across groups.

Notes

Participants could have multiple courses of pharmacotherapy; 23%, 33%, 23%, 12%, and 9% of participants requested 0, 1, 2, 3, or 4 courses, Disease management conditions increased use in first cycle and reduced it later. 41% of cycles used bupropion & 59% patch. Over 24 months average number of calls 3.6 in 2. and 8.2 in 3. Fewer calls in later cycles.

No evidence of effect based on PP, but some evidence of benefit when all follow-ups taken into account

High intensity vs control in main comparison. Moderate intensity quit almost identical (35/238 14.7%).

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk'computer generated random numbers table was utilized to generate allocation cards in blocks of 24 with allocation equally distributed across treatment groups'
Allocation concealment (selection bias)Low risk'cards were placed in sequentially numbered, opaque, sealed envelopes'
Incomplete outcome data (attrition bias)
All outcomes
Low riskLess than 20% lost to follow-up, similar distribution amongst groups (11% control, 16% in both moderate and high intensity intervention arms)

Fiore 2004

MethodsSetting: Primary care patients, 16 clinics, USA
Recruitment: Clinic attenders willing to accept treatment
Participants961 smokers of >=10 cpd. (A further 908 were allowed to select treatment, not included in review. Demographic details based on 1869.) 58% F, av. age 40, av. cpd 22
Therapists: Trained cessation counsellors
Interventions

Pharmacotherapy: NRT (patch, 22mg, 8 wks incl tapering)

1. NRT alone
2. As 1 plus Committed Quitters programme, single telephone session and tailored S-H.
3. As 2 plus face-to-face individual counselling, 4 x 15-25 min sessions, pre-quit, ˜TQD, next 2 wks.

OutcomesContinuous abstinence at 1 yr (no relapse lasting 7 days), also PP.
Validation: CO, cut-off not specified. 2 discordant
Notes3 versus 1 used in primary analysis. 3 & 2 versus 1 is more conservative since 2 had lower quit rates than 1. Use of PP outcome does not alter findings.
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
Incomplete outcome data (attrition bias)
All outcomes
Low riskPeople who did not pick up patches were excluded from analyses, similar distribution amongst groups (17% control, 16% in intervention arm 1, 14% intervention arm 2). No reported loss to follow-up for remaining participants.

Gariti 2009

MethodsSetting: academic research centre, USA
Recruitment: community volunteers, interested in quitting
Participants

260 light smokers (6-15 cpd), 57% F, av. age ˜43, av. cpd 11, approx 1/3 smoked <10 cpd, approx 50% had history of smoking 20 cod

Therapists: Cessation counsellors

Interventions

2x2 double-blind double-dummy. Participants randomized to either nicotine patch (21 mg/day or 14 mg/day (< 10 cpd) for 8 wks incl weaning) or bupropion (9 wks).

1. Pharmacotherapy & medication management, 4 x 5-10 min visits over 6 wks

2. Pharmacotherapy & counselling, 10 weekly individual 10-15 mi sessions

Outcomes

Abstinence at 1yr, sustained with no relapse of over 7 days smoking. (Study primary outcome is PP abstinence)

Validation: CO ≤ 9 ppm & cotinine (NicAlert) ≤ 200 ng/ml or cotinine <50 ng/ml

NotesNRT & bupropion conditions not reported separately by counselling condition, so 2 vs 1 entered in NRT or bupropion section. Favoured NRT but no significant difference at any follow-up. More evidence of effect on sustained than PP rates at 1yr, but substituting PP in MA does not affect findings.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskComputer generated 'urn' randomization by independent data analyst
Allocation concealment (selection bias)Low riskRandomization after enrolment, not predictable
Incomplete outcome data (attrition bias)
All outcomes
Low risk108 (84%) intervention and 108 (82%) control reached at 1 year.

Ginsberg 1992

MethodsSetting: academic research centre, USA
Recruitment: Community volunteers
Participants99 smokers with an acquaintance willing to participate as a support partner; 54% F, av. age 38, av. cpd 26
Interventions

Pharmacotherapy: Nicotine gum, 2 mg, duration not specified

1. Instruction for gum use & educational materials, 2 brief sessions over 2 wks
2. Instructions as 1. included with a group based behavioural programme including skill training, 5 sessions over 4 wks. Duration not specified, assumed to be 91 to 300 min.
3. As 1. plus behavioural programme and partner support programme, 8 sessions over 5 wks. Not included in this review

OutcomesAbstinence at 52 wks (not clear if abstinence required at prior assessment at wks 4,12, 26)
Validation: CO < 10ppm, urine cotinine < 50ng/mL. Paper states that cotinine levels failed to confirm self report in 7 people, 3 of whom were still coded as abstinent on the balance of evidence.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear risk'randomly assigned to 3-6 member groups in order of entrance into treatment within time constraints. Treatment for each group was randomly selected ...'
Allocation concealment (selection bias)Unclear riskNo details reported
Incomplete outcome data (attrition bias)
All outcomes
Low risk9 participants lost to follow-up counted as smokers. 1 participant who died excluded from analyses.

Hall 1985

MethodsSetting: Clinic, USA
Recruitment: referred by physicians, friends or self
Participants84 smokers in relevant arms; 53% male, av. age 38, av. cpd 30.5
Therapists: 2 psychologists
Interventions

Pharmacotherapy: NRT; gum (2 mg, available for 6 m)

1. Intensive behavioural treatment (incl relapse prevention skill training, relaxation, 30 seconds aversive smoking of 3 cigs). 14 x 75 min sessions over 8 wks
2. Low-contact . Met x4 in 3w, educational materials, written exercises, group discussion

3. Intensive behavioural, no gum. Not included in this review

OutcomesAbstinence at 52 wks (assume PP)
Validation: CO < 10ppm, thiocyanate < 85 mg/ml, reports of significant others (biochemical measures failed to confirm self-report in 3 instances)
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk'Randomly assigned within time constraints.' Author clarification: 'There were two or more treatment conditions available within any time block, and participants were randomly assigned to conditions within that time block'.
Allocation concealment (selection bias)Unclear riskNo details given
Incomplete outcome data (attrition bias)
All outcomes
Low risk3 dropouts from group 2 and 3 from group 3. 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% male, av. age 39, av. cpd 30 (71 in relevant arms)
Therapists: Advanced graduates in clinical psychology or health psychology
InterventionsPharmacotherapy: NRT (gum). Placebo arms of factorial trial not used in review
1. Intensive behavioural treatment,14 x 75 min sessions (period not stated) (incl 6 seconds aversive smoking, RP skills training, written exercises)
2. 'Low contact' 5 x 60 min sessions (incl written exercises, educational materials, group discussions, quitting techniques)
OutcomesAbstinence at 52 wks (assume PP)
Validation: thiocyanate < 95mm/L (unless marijuana use reported), CO < 8ppm, significant other.
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 reported
Incomplete outcome data (attrition bias)
All outcomes
Low risk2 dropouts in 1 & 2 in 2 included in ITT analyses. "Differences between conditions were not statistically significant."

Hall 1994

MethodsCountry: USA
Recruitment: Community volunteers or referrals
Participants149 smokers ( > 10 cpd)
52% F, av. age 41, av. cpd 25, 31% had history of MDD
Therapists: physician, psychologist. Both received training
Interventions

Pharmacotherapy: NRT (gum, 2 mg for up to 12 wks, tapering from wk 4)
1. Mood Management. 10 x 2 hr sessions over 8 wks. Similar to control, plus specific cognitive-behavioural components for developing skills for coping with situations leading to poor mood. Thought stopping, rational-emotive techniques, relaxation etc.

2. Standard group therapy. 5 x 90 min sessions over 8 wks. Information and group support for planning and implementing individual strategies.

OutcomesContinuous abstinence at 52w. (Confirmed quit at all prior assessments and no smoking in previous wk)
Validation: CO ≤10 ppm and urine cotinine ≤60 ng/ml
NotesBoth behavioural interventions were relatively intensive. Positive effect reported for subgroup with history of major depression.
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
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskDropouts included as smokers, but numbers not specified

Hall 1998

MethodsSetting: Cessation clinic, USA
Recruitment: Community volunteers. Exclusion criteria included MDD within 3m of baseline
Participants199 smokers of ≥ 10 cpd; 55% F, av. age 40, av. cpd 21-25; 33% had history of MDD
Therapists: 3 doctoral level clinical psychologists
Interventions

Pharmacotherapy: Nortriptyline (titrated to therapeutic levels - usually 75-100 mg/day for 12 wks). Placebo arms of factorial trial not used in review
1. Mood Management. 10 x 2 hr sessions over 8 wks.

2. Standard group therapy control. 5 x 90 min sessions over 8 wks. (See Hall 1994 for description of each intervention)

OutcomesAbstinence at 64 wks (1 yr post-treatment). Continuous abstinence rates not reported by psychological treatment group.
Validation: CO < 10ppm and cotinine < 341 nmol/L
NotesBoth behavioural interventions were relatively intensive.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandomized by computer, after stratification on history of MDD and number of cigs smoked
Allocation concealment (selection bias)Low riskComputer randomization after data collection
Incomplete outcome data (attrition bias)
All outcomes
Low risk16% lost to follow-up at 1 yr, no difference by group, included in denominators for MA

Hall 2002

MethodsCountry: USA
Recruitment: Community volunteers. Exclusion criteria included current MDD
Participants220 smokers (146 in relevant arms); ≥ 10 cpd; 40-47% F, av. age 37-43, av. cpd 20-23; 33% had history of MDD
InterventionsPharmacotherapy: Bupropion (300 mg for 12 wks) or Nortriptyline (titrated to therapeutic levels, typically 75 or 100 mg/d). Factorial 3x2 design, placebo arms not used in this review
1. Medical Management (MM) control: physician advice, S-H, 10-20 min 1st visit, 5 min at 2, 6, 11 wks)
2. Psychological Intervention (PI) as MM plus 5x 90 min group sessions in wks 4, 5, 5, 7 & 11)
OutcomesPP abstinence at 1 yr (47 wks post-quit date). Continuous abstinence not reported by subgroup
Validation: CO ≤10 ppm, urine cotinine ≤ 60 ng/mL
NotesBupropion PI vs MM & nortriptyline PI vs MM used in relevant subgroups. Trial also contributes to review of combined interventions Stead 2012a, using different combination of arms
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomized, method not specified, 'double blind'
Allocation concealment (selection bias)Unclear riskNo details given
Incomplete outcome data (attrition bias)
All outcomes
Low risk19% lost to follow-up at 12m, similar numbers across groups

Hall 2009

Methods

Setting: Cessation clinic, USA

Recruitment: Community volunteers

Participants402 smokers (≥ 10 cpd) aged ≥ 50; 40% F, av. age 57, av. cpd 21
Interventions

Pharmacotherapy: NRT (gum, 10 wks, 2 or 4 mg) & bupropion (12 wks). 2 arms had extended access to gum.

1. 'Standard treatment'; 5 group sessions over 8 wks, 'Clear Horizons' manual

2. Extended CBT; 11 individual 20-40 min sessions from wk 10 – wk 52, schedule front loaded. Incl motivation, mood management, weight control, social support, coping with withdrawal.

3. Extended NRT. Nicotine gum available until wk 52, no additional behavioural support

4. Extended Combined, CBT & NRT; 3 & 4

Outcomes

Abstinence at 104 wks (one year after end of all treatment) (PP)

Validation: CO ≤ 10 ppm and urine anatabine/anabasine ≤ 2 mg/ml

NotesMeta-analysis comparison is 2 & 4 vs 1 & 3
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandomized at end of initial treatment, computerized allocation list by statistician who had no contact with participants. Stratified on gender, history of MDD, current cigarette abstinence status.
Allocation concealment (selection bias)Low risk'The assignment of individual participants by subject number was then transmitted electronically to clinical staff.'
Incomplete outcome data (attrition bias)
All outcomes
Low riskLess than 20% lost to follow-up in each group, denominator excludes participants who died during the study but counts all others lost to follow-up as smokers.

Hollis 2007

MethodsSetting: Community-based telephone quitline programme, Oregon, USA
Recruitment: Callers invited to participate; assumed to be fully or partly motivated to quit
Participants

4614 smokers randomized to: brief counselling (872, no NRT; 868, with NRT); moderate counselling (718, no NRT; 715, with NRT); intensive counselling (720, no NRT; 721, with NRT).

40% male, av. age 41, 90% white, av. cpd 21.

InterventionsFactorial design; Arms that were offered free NRT (patches, initial 5 wk supply, 3 more wks available) contribute to this review
Intervention 1. Brief counselling (usual care), 15 min call + referral material + tailored S-H materials.
Intervention 2. Moderate counselling: 40 mins counselling based on MI + 1 brief call to encourage use of community services, tailored S-H materials.
Intervention 3. Intensive counselling: As 2, plus offer of up to 4 additional telephone calls. Each call incorporated MI techniques, stage assessment, relapse prevention as needed.
Outcomes30-day PPA at 6 and 12m
Validation: none
Notes

3 vs 1 in main comparison. Actual contact in 3; mean 2.9 sessions, 60.6 min contact

Also contributes to review of combined interventions Stead 2012a.

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk"a computer algorithm randomly assigned participants"
Allocation concealment (selection bias)Unclear riskNot stated
Incomplete outcome data (attrition bias)
All outcomes
Low riskModerate level of attrition but balanced between groups, and participants lost to follow-up counted as smokers (72% followed up in groups 1 and 2, 68% followed up in group 3)

Huber 2003

MethodsSetting: Academic research centre, Germany
Recruitment: Community volunteers
Participants225 smokers (102 in relevant arms); 55% F, av. age 38, av. cpd 28
Interventions

Pharmacotherapy: nicotine gum, 2 or 4 mg

1. 5 x 90 min weekly meetings. Included contracting, reinforcement, relaxation, skills training.
2. Same schedule of meetings, 45 min only, focus on sharing experiences.
3. As 1, no nicotine gum. Not included in this review

4. Wait-list control for 6 months. Not included in this review

OutcomesPP abstinence at 12m
Validation: CO ≤ 4ppm
NotesControl and intervention fall into same categories for number and duration of sessions
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
Incomplete outcome data (attrition bias)
All outcomes
Low risk31 people attending 2 or fewer meetings not included in analysis. Said to be evenly distributed. Later drop-outs included as smokers; 90% of those receiving therapy (excludes wait list group 4, who are also excluded from this review) followed up at 12m.

Jorenby 1995

MethodsCountry: 2 academic research sites, USA
Recruitment: Community volunteers
Participants504 smokers (≥ 15 cpd); ˜53% F, av. age 44, av. cpd 26-29
Therapists: Trained smoking cessation counsellors
InterventionsCompared 22 mg vs 44 mg nicotine patch and 3 types of adjuvant treatment. Patch groups collapsed. All participants had 8 weekly assessments by research staff
1. Minimal: Given S-H pamphlet by physician during screening visit for trial entry, and instructed not to smoke whilst wearing patch. No further contact with counsellors.
2. Individual: Given S-H pamphlet at screening visit along with motivational message. Also met nurse counsellor x3 following quit date. Nurse helped generate problem-solving strategies and provided praise and encouragement.
3. Group: Given S-H pamphlet at screening visit along with motivational message. Received 8x 1hr weekly group sessions. Skills training, problem-solving skills.
Outcomes7 day PP abstinence at 26 wks
Validation: CO < 10 ppm.
NotesNo significant difference in dose-related outcome and no dose-counselling interaction at 26 wks reported. Patch arms collapsed in analysis. 3 vs 1 used in primary comparison, RR 0.99 [0.69, 1.42]. RRs for other comparisons: 2&3 vs 1 = 1.10 [0.81, 1.49], 2 vs 1 = 1.21 [0.86, 1.70], 3 vs 2 = 0.82 [0.58, 1.15]
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandomized, method not stated
Allocation concealment (selection bias)Unclear risk'In a double blind manner' for NRT, but not specified for counselling
Incomplete outcome data (attrition bias)
All outcomes
Low riskLosses not specified by group, relatively low rate lost to follow-up overall (16.3%), Counted as smokers in report & MA.

Killen 2008

Methods

Setting: Community cessation clinic, USA

Recruitment: Community volunteers

Participants301 smokers (≥ 10 cpd or 3.5 packs/wk) (excludes 3 participants who received wrong treatment); 40% F, av. age ˜46, av. cpd ˜20
Interventions

Pharmacotherapy: Bupropion (300 mg, 9 wks) & NRT (21 mg patch, 8 wks incl tapering) 

Common behavioural therapy: 6 x 30 min individual CBT sessions at baseline, TQD, 1, 2, 4, 6 wks

1. Extended therapy: 4 x 30 min sessions at 8, 12, 16, 20 wk, & weekly check in calls to automated system; report of relapse or craving prompted proactive calls

2. Control: 5 min general support calls at 8, 12, 16, 20 wks

Outcomes

Abstinence at 52 wks (7 day abstinence at both 20 & 52 wks) (Continuous abstinence also reported but not used in MA as could underestimate any effect on recycling)

Validation: CO < 10 ppm (11 self reported quitters no longer living in study area accepted as quitters without validation)

NotesTested of extended duration therapy.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandomized using a permuted block method (block size = 4), stratified on gender
Allocation concealment (selection bias)Low riskParticipants assigned to next available ID number in corresponding gender. Researchers & participants were blinded to extended treatment assignment to the end of the open-label phase.
Incomplete outcome data (attrition bias)
All outcomes
Low risk89% followed up in standard care group, 90% followed up intervention group

Lando 1997

MethodsSetting: Health Maintenance Organization, USA
Recruitment: Physician referral and HMO clinic newsletters
Participants509 smokers of > 20 cpd, motivated to quit; 56% F, av. age 42, av. cpd 28
InterventionsAll participants received prescriptions for free nicotine patch (Prostep), 22 mg for a maximum of 6 wks plus 11mg for 2 wks. All attended 90 mins group orientation session describing study, use of patch, behavioural information, set quit date. Standard written materials with patch included description of a toll-free telephone help line.
1. No further support
2. Orientation session included encouragement to call toll-free number and a registration card
3. Additional proactive telephone counselling, 4 10-15 min calls (approx 1, 4, 7-9, 12 wks from quit date). Reinforced success or negotiated a new quit date.
OutcomesAbstinence at 12m (from quit date)
Validation: CO at 6m. 96% of quitters were confirmed.
Notes

Also contributes to Cochrane review of telephone counselling (Stead 2006).

Effect of counselling compared to contact & quitline alone. (1& 2 combined since fewer than 1% called quitline and no difference between quit rates.) Participants who did not return questionnaires at 2, 5, 8, 12 wks were called by telephone.
Average number of calls completed 3.76.

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskCluster randomized, method not described
Allocation concealment (selection bias)Unclear riskAllocation by orientation session attended; participants did not know condition in advance so risk of selection bias probably low
Incomplete outcome data (attrition bias)
All outcomes
Low risk82% response rate at 12m, no difference between groups, missing treated as smoking

Lifrak 1997

MethodsSetting: substance abuse outpatient facility, USA
Recruitment: Community volunteers
Participants69 smokers; 61% F, av. age 39, av. cpd 25
InterventionsPharmacotherapy: nicotine patch (24 hr, 10 wks 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 relapse prevention therapy from clinical social worker or psychiatrist experienced in addiction treatment.
OutcomesAbstinence at 12m, 1 wk PP
Validation: urine cotinine for some participants, but no corrections made for misreporting.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskBlock randomization (block size 10)
Allocation concealment (selection bias)Unclear riskNo details given
Incomplete outcome data (attrition bias)
All outcomes
Low riskLow rate of attrition (though breakdown by group not provided): 12 administrative dropouts/exclusions not included in analyses

Lloyd-Richardson 2009

MethodsSetting: 6 outpatient HIV clinics & 2 primary care clinics, USA
Recruitment: Eligible patients identified by physicians, motivation to quit not required
Participants444 HIV+ smokers; 37% F, av. age 42, av. cpd 18
Interventions

Pharmacotherapy: Nicotine patch for up to 8 wks if willing to set quit date.

1. 2 brief counselling sessions, biweekly patch collection without counselling contact

2. 4 x 30 min sessions + quit day call, using motivational interviewing approach

Outcomes

Abstinence at 6m (PP)

Validation: CO < 10 ppm

Notes72% used patch at some point during study
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskBlock randomized, stratified by gender & motivation to quit
Allocation concealment (selection bias)Unclear riskNo details provided
Incomplete outcome data (attrition bias)
All outcomes
Low risk75% intervention, 71% control followed up at 6m. ITT and available case analyses reported.

MacLeod 2003

MethodsSetting: Community, Australia
Recruitment: Community volunteers
Participants854 smokers interested in quitting; 51% F, av. age 42, av. cpd 24
Interventions

All participants received a free 2 wk supply of nicotine patch by mail, instructed to purchase further supply. 14 or 21 mg depending on body weight.

1. No further intervention
2. As 1. + 5 proactive telephone counselling calls 1, 2, 3, 6 & 10 wks. 20 min session 1, 10 min others. Toll-free hotline, S-H materials.

OutcomesAbstinence at 6m (90-day continuous)
Validation: none, warning of CO test only.
NotesAlso contributes to Cochrane review of telephone counselling (Stead 2006). No face-to-face contact.
Average number of calls 4.7. 9% of participants called hotline.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk'Randomized' by shuffling folders each day after participants to be included were listed. Since there was no personal contact with participants risk of bias judged to b low
Allocation concealment (selection bias)Low riskPotential for bias since allocation sequence not fixed in advance, however baseline characteristics similar across groups so no evidence of selection bias.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo significant difference in loss to follow-up, 17% in NRT only, 15% in NRT+ at 6m

McCarthy 2008

MethodsSetting: Clinic, USA
Recruitment: Community volunteers
Participants463 smokers; 50% F, av. age 36-41 across arms, av. cpd 22
Therapists: trained college-aged or bachelor's level staff, supervised by experienced counsellor
InterventionsFactorial trial of bupropion or placebo pharmacotherapy and counselling versus support
1. Bupropion & counselling; 13 office visits, 8 included additional 10 min counselling, 2 prequit, TQD, 5 over 4 wks (classified as > 300 mins contact)
2. Bupropion & psychoeducation about medication, support & encouragement. 13 office visits, 80 mins less contact time than 1. (classified as 91 to 300 mins contact)
3. Placebo & counselling. Not included in this review
4. Placebo & psychoeducation. Not included in this review
Outcomes7 day PP abstinence at 12m (Prolonged abstinence reported but not verified so PP used in MA)
Validation: CO ≤ 10ppm
Notes1 vs 2 used as test of adjunct behavioural support.
Also contributes to Cochrane reviews of combined interventions (1 vs 4) (Stead 2012a), antidepressants (collapsing behavioural conditions) (Hughes 2007) and individual behavioural counselling (collapsing pharmacotherapy) (Lancaster 2005b).
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandom number table
Allocation concealment (selection bias)Low riskStaff who screened and enrolled participants were unaware of the experimental condition to be assigned
Incomplete outcome data (attrition bias)
All outcomes
Low risk63% reached at 12m, but attrition rates did not differ by condition at any point

Ockene 1991

MethodsSetting: Primary care clinics, USA
Recruitment: Clinic attenders, not selected for interest in quitting
Participants380 smokers in relevant arms (excludes deaths and some who did not receive intervention); of 1223 smokers in study; 57% F, av. age 35, av. cpd 23
Interventions

Pharmacotherapy: Nicotine gum; offer of free gum

2x3 factorial design, physician intervention +/- follow-up.
1. Physician counselling (initial session and 1 follow- up) and offer of NRT. Follow-up telephone counselling by psychologist or health educator, 3 calls (1, 2, 3m) approx 10 mins, behavioural recommendations. Letters.
2. Physician counselling as 1. No additional follow-up.

OutcomesAbstinence at 6m (7-day); (3m sustained abstinence rates not given by condition)
Validation: none
Notes

Marginal to include since relatively low use of pharmacotherapy; in intervention condition, of those reached, 33% refused use and 18% tried for 2 days or less.

12m abstinence rates reported in Ockene 1994 but not given by follow-up condition. Also contributes to review of combined interventions (Stead 2012a).

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomized, method not described
Allocation concealment (selection bias)Unclear riskAllocated prior to physician encounter
Incomplete outcome data (attrition bias)
All outcomes
Low risk19% lost to follow-up, higher in telephone follow-up group. All included as smokers in analysis.

Otero 2006

MethodsSetting: Brazil
Recruitment: Community volunteers
Participants1199 smokers (includes 254 non-attenders); 63% F, av. age 42, 46% smoked > 20 cpd
Therapists: trained doctors, nurses or psychologists
InterventionsFactorial design with NRT (21mg or 14mg patch for 8 wks incl tapering) or no NRT and 5 levels of behavioural support collapsed into 3 for analysis. Arms without NRT do not contribute to this review.
1. Single 20 min session - classified as brief intervention control in meta-analysis
2. Cognitive behavioural, 1 or 2 weekly x1 hr sessions
3. As 2, with 3 or 4 weekly sessions.
Maintenance or recycling sessions provided to all groups at 3, 6, 12m.
OutcomesAbstinence at 12m (7 day PP)
Validation: none
Notes3 vs 1 in patch condition only in primary analysis. Also contributes to review of combined interventions (Stead 2012a).
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandomized, stratified by age & sex, by independent specialist
Allocation concealment (selection bias)Low riskTrial administrators blind
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNumber lost to follow-up not provided. Non-participants and losses to follow-up included as smokers.

Reid 1999

MethodsSetting: Community, Canada
Recruitment: Volunteers
Participants396 smokers interested in quitting within 30 days, smoking ≥15 cpd; 48% F, av. age 38, av. cpd 23-24
Interventions

Pharmacotherapy: NRT; patch (15mg x 8 wks, 10mg x 2 wks, 5mg x 2 wks) free

1. Physician advice (3x 15 min, 2 wks before, 4 wks, 12 wks after quit date)
2. As 1, plus telephone calls from nurse counsellors, x 3 at 2, 6, 13 wks.

OutcomesAbstinence at 12m (PP)
Validation: CO, but self-reported rates reported. Only 1 disconfirmation.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomized using table of random numbers, stratified by sex and nicotine dependence
Allocation concealment (selection bias)Unclear riskConcealment unclear but physician blind to allocation
Incomplete outcome data (attrition bias)
All outcomes
Low risk84% intervention 86% control followed-up at 12m

Rovina 2009

MethodsSetting: Smoking cessation clinic, Greece
Recruitments: Clinic attenders invited to participate
Participants205 smokers
Interventions

Pharmacotherapy: Bupropion 300mg/day for 19 wks

1. Control: 15 mins physician counselling

2. Nonspecific group therapy (NSGT), 1 hour weekly for 1 m, then every 3 wks until 19 wks

3. Cognitive behavioral group therapy (CBGT), same schedule

4. CBGT without bupropion - not used in review

Outcomes

Abstinence at 12m after end of treatment (continuous)

Validation: CO ≤ 10 ppm

Notes2 & 3 vs 1 in primary analysis, same intensity
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomised, method not stated, 3:1:1:1 ratio
Allocation concealment (selection bias)Unclear riskNo details reported
Incomplete outcome data (attrition bias)
All outcomes
Low risk90% followed up at 12m

Simon 2003

MethodsSetting: Hospital for military veterans, USA
Recruitment: Inpatients (all diagnoses) invited to participate
Participants223 smokers, ≥ 20 cigarettes in wk before admission, contemplation or action stage of change, able to use NRT. Av. age 55, av. cpd 23.
Interventions

Pharmacotherapy: NRT; patches (tailored dose) in hospital and for 8 wks post discharge

1. Intervention: Nurse or health educator counselling; 30-60 mins initial session. 5 calls at 1, 3 wks, 1m, 2m, 3m, < 30 min/call & S-H materials
2. Control: brief counselling (10 mins) + S-H only

OutcomesAbstinence: 7-day PP at 12m
Validation: Saliva cotinine <15 ng/ml (alternative analysis allowed spousal corroboration)
NotesRelative effect similar if spousal corroboration allowed
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandomized using computer algorithm
Allocation concealment (selection bias)Unclear riskNo details reported
Incomplete outcome data (attrition bias)
All outcomes
Low riskLosses to follow-up (3 intervention, 4 control) included as smokers. Deaths (5 intervention, 9 control) excluded from denominator.

Smith 2001

MethodsSetting: Clinic, USA
Recruitment: community volunteers
Participants677 smokers (> 10/day) attempted quit for 1 wk; 57% F, av. age 42; av. cpd 25
InterventionsPharmacotherapy: NRT, patches for 8w. All participants had attended 3 brief (5-10 min) individual counselling sessions pre-quit, quit day and 8 days post-TQD & NCI booklet 'Clearing The Air'.
1. Cognitive behavioural skills training, x 6 from 1 wk post-TQD, incl managing negative affect, homework, manual.
2. Motivational interviewing, supportive group counselling, x 6 from 1 wk post-TQD. No homework or manual.
3. No further intervention
OutcomesAbstinence at 12m (7 day PP)
Validation: CO < 10ppm
Notes

Marginal to include as the counselling was intended for relapse prevention.

1 vs 3 in primary analysis. Including 2 does not alter findings; 17.6% quit in 1, 18.8% in 2. No evidence found for hypothesized 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 riskRandomized 1 wk after TQD, stratified by +/- any smoking post-TQD. Method not stated
Allocation concealment (selection bias)Unclear riskNo details given
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNumber lost to follow-up not reported, all missing included as smokers.

Solomon 2000

MethodsSetting: Community, USA
Recruitment: Volunteers for free nicotine patch trial
Participants214 female smokers, > 4 cpd, intending to quit in next 2 wks; av. age 33, av. cpd 24
Interventions

Pharmacotherapy: NRT; Free nicotine patch (dose based on smoking level) for up to 10 wks, After 1 month contingent on abstinence

1. Access to Nicoderm support line
2. As 1. and Proactive telephone counselling from female ex smoker, 7 hrs training. Up to 12 calls for up to 3m, starting pre quit, quit day, day 4, average 7.

OutcomesAbstinence at 6m (Multiple PP; 7 days at 3m & 6m)
Validation: CO ≤ 8ppm. 7-12% disconfirmation rate. Participants who did not provide samples remained classified as quitters.
NotesIntervention participants received on average 7 calls of 9 mins. Classified in 4-8 subgroup analysis. 95% received at least 1 call. Participants could call Nicoderm support line, 21% of control vs 8% of intervention did so.
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
Incomplete outcome data (attrition bias)
All outcomes
Low riskApproximately 73% followed up in each group

Solomon 2005

MethodsSetting: Community, USA
Recruitment: Volunteers for free nicotine patch trial
Participants330 female smokers > 4 cpd, intending to quit in next 2 wks; av. age 34, av. cpd 24
Interventions

Pharmacotherapy: NRT; Free nicotine patch (dose based on smoking level) for up to 10 wks, 2nd & 3rd prescriptions dependent on reporting abstinence

1. No additional support
2. Proactive telephone counselling from female ex smoker, 8 hrs training. Calls for up to 4m, starting pre quit, quit day, day 4

OutcomesAbstinence at 6m (30 days at 3m & 6m)
Validation: none
NotesSimilar to Solomon 2000 with more extended telephone contact.
Average number of calls 8.2, average duration 10 min. Classified in 4-8 subgroup analysis.
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
Incomplete outcome data (attrition bias)
All outcomes
Low risk87% response in both conditions at 6m

Stein 2006

MethodsSetting: 5 methadone maintenance treatment programme centres, USA
Recruitment: Smokers routinely attending maintenance clinic. Willingness to quit not required.
Participants383 methadone-maintained adult smokers. 53% M, av. age 40, av. cpd 27
InterventionsPharmacotherapy: NRT; all participants willing to make quit attempt offered patches (8-12 wks, dose and duration tailored to smoking rate)
1. Motivational interview based tailored Intervention: Up to 3 visits from study counsellor, i.e. 1 x 30-min + 15-30 min quit date session, + follow-up relapse prevention session. Those not ready to quit only received 2 sessions.
2. Control: Brief advice using NCI's 4 As model (<3 minutes), + S-H materials. Up to 2 visits, i.e. baseline and quit date (if set).
OutcomesAbstinence at 6m (PP)
Validation: CO < 8ppm
NotesIncluded since most participants in both conditions did make quit attempts and receive NRT; 81% intervention and 80% control.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomized, methods not stated
Allocation concealment (selection bias)Unclear riskNo details reported
Incomplete outcome data (attrition bias)
All outcomes
Low riskApprox 82% followed-up in both groups at 6m

Swan 2003

MethodsSetting: HMO, USA
Recruitment: Volunteers from Group Health Co-op membership
Participants1524 smokers ≥ 10 cpd; 57% F, av. age 45, av. cpd 23, 44% history of depression
InterventionsPharmacotherapy: Randomized to bupropion 300 mg/day or 150 mg/day
1. Free & Clear proactive telephone counselling (4 brief calls), access to quitline and S-H materials
2. Zyban Advantage Program (ZAP); tailored S-H materials, single telephone call after TQD, access to Zyban support line
OutcomesAbstinence at 12m (7-day PP)
Validation: none
Notes

Prescription was mailed. No face-to-face contact during enrolment or prescription. Estimated as 31-90 minutes contact.

No dose/behavioural treatment interaction at 12m, bupropion arms collapsed.

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk"Open-label randomized trial...The computer code for the procedure calculated probabilities of group assignment that were dynamically modified based on the number of members in each group so that final group sizes were equal. No restrictions such as stratification or blocking were used as part of the randomization process."
Allocation concealment (selection bias)Low riskProcedure built into study database
Incomplete outcome data (attrition bias)
All outcomes
Low risk83% intervention, 88% control followed up at 12m

Swan 2010

Methods

Setting: HMO (Group Health), Seattle, WA, USA

Recruitment: Group Health members contacted by phone & mail from Free & Clear

Participants1202 smokers (≥ 10 cpd); 67% F, av. age 47, av. cpd 22
InterventionsPharmacotherapy: varenicline for 12 wks (1 mg x 2/day, titrated 1st wk). All received 5-10 min orientation call, printed Quit Guides and access to a free support line for ad hoc calls.
1. Web-based counselling: Access to online programme, including quit plan, online library, quit calendar, cost calculator, progress tracker, email links to friends and family and discussion forums.
2. Proactive telephone-based counselling: Free & Clear Quit for Life program. Up to 5 'brief' one-to-one phone sessions initiated by F&C counsellor. Timed for convenience and at relapse-sensitive stages. Used MI techniques.
3. Combination: Proactive calls + web access; counsellor could view info entered online. Participants encouraged to use website for additional info and social support, and to track CPD. Counsellors could view quit status, last log-in and last use of discussion forum.
OutcomesAbstinence at 6m (PP)
Validation: none
Notes

3 vs 1 in main analysis, 2&3 vs 1 has little effect on result. 60 min contact on average for 3.

64% were no longer taking varenicline at 3m, but no between-group differences in non-compliance or reasons for stopping.

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk"Group assignment was randomly allocated using an automated algorithm built into the study database"
Allocation concealment (selection bias)Unclear riskNot stated
Incomplete outcome data (attrition bias)
All outcomes
Low riskParticipants lost to follow-up counted as smokers in ITT analysis; equal losses between groups (103 Web, 107 Phone, 100 Web + Phone)

Tonnesen 2006

MethodsSetting: 7 chest clinics, Denmark
Recruitment: Outpatient attender
Participants

370 smokers of > 1 cpd with COPD (185 in relevant arms); 52% F, av. age 61, av. cpd 20

Therapists: 20 nurses with cessation experience, trained to support medication use and provide standardised counselling

InterventionsPharmacotherapy: NRT; sublingual. Factorial trial included placebo tablets, only active treatment groups used in this review
1. High support: 7 x 20-30 min clinic visits (0, 2, 4, 8, 12 wks, 6m, 12m) & 5 x 10min phone calls (1, 6, 10 wks , 4½m. 9m), total contact time 4½ hrs.
2. Low support: 4 clinic visits (0, 2 wks, 6m, 12m) & 6 phone calls (1, 4, 6, 9, 12 wks, 9m), total time 2½ hrs.
OutcomesSustained abstinence at 12m (validated at all visits from wk 2, PP also reported)
Validation: CO < 10ppm
NotesAlso contributes to review of combined therapy review (Stead 2012a), using Placebo low support arm as control. Therapists were not full-time specialist counsellors. Using PP outcome does not alter effect. Only contacts before 12 weeks counted for classification of intensity.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskBlock randomization list at each centre
Allocation concealment (selection bias)Unclear riskAllocation process not described
Incomplete outcome data (attrition bias)
All outcomes
Unclear risk42/185 (23%) of active NRT participants not followed-up at 12m and counted as smokers. Not reported by support condition. Of those who were followed up at 12m, 52% had withdrawn from study treatment. Authors state: "One potential bias may have been the large early dropout of failures from the study. Consequently, these patients were not exposed to the possible effect of more intensive support."

Wiggers 2006

MethodsSetting: Cardiovascular outpatient department, Netherlands
Recruitment: Patients attending regular consultation; consenting patients referred to nurse practitioner
Participants385 smokers (8 deaths excluded from outcomes). 37% F, av. age 59, av.cpd 21
Therapist: nurse practitioner
InterventionsPharmacotherapy: NRT; patch (8 wks, dose based on smoking rate) for smokers making a quit attempt. In both groups, patients planning to quit received 8 wks nicotine patch with instruction from nurse.
1. 'Minimal Intervention Strategy for cardiology patients (C-MIS). 15-30 mins at baseline, 1 phone call at 2 wks, additional session on request. Assessment of dependency & motivation, barriers; TQD set for motivated patients.
2. Usual care without motivational counselling,
OutcomesAbstinence at 12m (7 day PP)
Validation: Urine or saliva nicotine/cotinine/thiocyanate. Self-reported smokers also tested; validated rates include smokers with negative biochemical results, so self-reported non-smoking used in MA.
NotesParticipants were referred to nurse practitioner for counselling; not part of usual care. Unclear how many patients used NRT; in a subgroup who responded to a questionnaire (Wiggers Int J Behav Med 2006), 16% did not start patch therapy).
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk'A computerized balanced randomization programme taking prognostic factors (e.g. clinic attendance, age and gender) into account.'
Allocation concealment (selection bias)Low risk'While patients completed their baseline questionnaire (and signed a written informed consent) nurses randomly assigned ...' Judged low risk as patient data had to be entered.
Incomplete outcome data (attrition bias)
All outcomes
Low risk89% intervention and 85% control followed up at 12m. 8 deaths excluded from final denominators.

Williams 2010

Methods

Setting: Mental health outpatient clinics, USA

Recruitment: Patients with schizophrenia or schizoaffective disorder, willing to use NRT

Participants

100 smokers (> 10 cpd) using an atypical antipsychotic; 16% F, av. age ˜46, av. cpd 23

Therapists: trained mental health clinicians provided both conditions

Interventions

Pharmacotherapy: Nicotine patch (21 mg for 16 wks incl tapering)

1. Treatment of Addiction to Nicotine in Schizophrenia (TANS); 24 x 45 min individual counselling sessions over 26 wks

2. Medical Management (MM); 9 x 20 mins over 26 wks

Outcomes

Continuous abstinence at 12m

Validation: CO < 10 ppm

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk'adaptive urn randomization procedure that accounts for motivation, gender, ethnicity, and heavy versus light smoking status'
Allocation concealment (selection bias)Low riskJudged that process for randomization prevented prior knowledge of condition
Incomplete outcome data (attrition bias)
All outcomes
Low risk75% followed up at 12m, authors report "not different between groups"

Wu 2009

  1. a

    av: average; CBT: cognitive behavioural therapy; cigs: cigarettes; CO: carbon monoxide; cpd: cigarettes per day; F: female; HMO: health maintenance organisation; hr: hour; incl: included; ITT: intention to treat; M: male; m: month; MA: meta-analysis; MI: motivational interviewing; mins: minutes; NCI: National Cancer Institute; NRT: nicotine replacement therapy; NS: not specified; PP: point prevalence abstinence; S-H: self-help; TQD: target quit date; wk(s): week(s); yr: year.

MethodsSetting: Research unit for Asian health, NYC, USA
Recruitment: Via Asian Community Health Coalition member organisations
ParticipantsChinese smokers (any smoking in previous wk); 12% F, av. age 44, av. cpd NS, 25% smoked less than 10 cpd, 49% had never attempted to quit
Interventions

Pharmacotherapy: NRT. Patch for 8 wks (could start at any time in 6m period)

1. Culturally tailored counselling in Chinese, 4 x 60 min & S-H

2. Health education in Chinese: 4 x 60 min, including general health, nutrition, exercise & tobacco

Outcomes

Abstinence at 6m (PP)

Validation: CO < 6 ppm

NotesConditions had same contact time, but control did not focus on smoking
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskrandomized, method not stated
Allocation concealment (selection bias)Unclear riskdetails not reported
Incomplete outcome data (attrition bias)
All outcomes
Low risk10% intervention and 14% control lost to follow-up at 6m and counted as smokers in ITT analysis

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
  1. a

    CBT: cognitive behavioural therapy; NRT: nicotine replacement therapy.

Ahluwalia 2006Conselling conditions had same number of contacts and duration. Compared Motivational Interviewing and Health Education in a factorial trial with nicotine gum or placebo. (Results favoured HE (control) condition.)
Batra 2010Behavioural conditions were matched for number of sessions. Experimental intervention was tailored for at-risk subgroups, and included recommendation to use combination NRT. Standard treatment control recommended single type of NRT.
Bock 2008Only participants interested in quitting (17% at baseline) were offered NRT. Main intervention was motivational interviewing.
Borland 2008Pharmacotherapy was only offered to participants interested in quitting; 24% reported use.
Brown 2007Factorial trial of bupropion/placebo and mood management CBT or standard cessation CBT. Both behavioural interventions were intensive, and experimental treatment was specifically devised for people with depression
Buchanan 2004Only 3 months follow-up (42 participants).
Carlin-Menter 2011Only 3 months follow-up. Compared 2 versus 4 counselling callbacks for smokers calling a quitline who received up to 6 weeks of free NRT.
Chouinard 2005Pharmacotherapy was only offered to participants interested in quitting; 24% used.
Christenhusz 2007Pharmacotherapy differed by arm: control arm advised to use pharmacotherapy but had to pay for it, intervention arm provided with bupropion free of charge.
Cooney 2007Both pharmacotherapy and behavioural components varied by trial arm.
Cooper 2004Main study results have not been published.
Costello 2011Only 5 weeks follow-up. Compared two intensities of pharmacist led behavioural support for participants using NRT.
Fang 2006Only 3 months follow-up.
Ferguson 2012Use of pharmacotherapy was low; only 42.9% of those offered NRT reported receiving any and of those only 51.3% used every day. There was also little difference between number of calls completed between proactive and standard telephone counselling conditions.
Garvey 2012Both behavioural interventions were intensive and matched for contact time, differed only in scheduling of sessions.
Hall 1996Both behavioural interventions were intensive and matched for contact time.
Hall 2004Factorial trial crossing extended behavioural support (CBT) with medical management only, and nortriptyline or placebo, for one year, as adjuncts to nicotine patch and 5 group counselling sessions. Placebo arms could have been compared, but no other trials confounded behavioural support with placebo, and the support common to all conditions was also much more intensive than in other trials.
Hall 2011Similar design to Hall 2004: Factorial trial crossing extended behavioural support (CBT) with medical management only, and bupropion or placebo, as adjunct to nicotine patch and 5 group support sessions over 11 weeks. As with Hall 2004, placebo arms could have been compared, but no other trials confounded behavioural support with placebo, and the support common to all conditions was also much more intensive than in other trials.
Hegaard 2003Study population pregnant smokers, not eligible.
Ingersoll 2009Only 3 months follow-up. Test of motivational interviewing as adjunct to nicotine patch therapy for HIV+ smokers.
Japuntich 2006Intervention was access to an internet site; no person-to-person behavioural support.
Joseph 2004Intervention and control did not differ on use of pharmacotherapy or intensity of behavioural support. Test of timing in relation to alcohol dependence treatment.
Joyce 2008Test of reimbursement for pharmacotherapy and counselling.
Kim 2012Pilot study with only 30 participants.
Kinnunen 2008Main intervention was exercise, not eligible for this review. The matched contact control was not intended to include tangible cessation help, and recruitment to the standard care control was halted early.
Kotz 2009Tested a specific behavioural intervention; feedback of biomedical information.
Levine 2010Behavioural interventions were matched for intensity, specifically tested a weight related intervention.
Marshall 1985Only offer of nicotine gum.
Mochizuki 2004Only 3 months follow-up. Small study of pharmacist advice as adjunct to NRT.
Nilsson 1996Only 4 months follow-up. Intervention was offer of group support and free NRT.
Nollen 2011Only 3 months follow-up. Study of an intervention to increase adherence to varenicline.
Okuyemi 2006All participants received same intensity of motivational interviewing, group sessions and offer of NRT. Tested different targets for motivational interviewing.
Reid 2007Intervention participants did not automatically receive additional behavioural support; intervention consisted of automated telephone calls to identify participants at risk of relapse. Only this subgroup then received further counselling.
Schmitz 2007All participants received same intensity of group based therapy, compared cognitive behavioural to supportive approaches.
Schnoll 2005Only 3 months follow-up, behavioural interventions similar in intensity as adjuncts to nicotine patch.
Shiffman 2000Only 12 weeks follow-up from start of treatment. Study of computer tailored materials as adjunct to nicotine gum.
Shiffman 2001Only 12 weeks follow-up from start of treatment. Study of computer tailored materials as adjunct to nicotine patch.
Sorensen 2003Short follow-up (pre-operative period).
Strecher 2005Only 12 weeks follow-up from start of treatment. No personal behavioural support, study of web-based tailored materials as adjunct to nicotine patch.
Velicer 2006Intervention was automated telephone counselling messages, no personal contact.
Vial 2002Compared intervention from two different types of pharmacist, not between different intensities of support.
Ward 2001Compared two group based behavioural interventions similar in intensity as adjuncts to nicotine patch, See Stead 2005.
Wilson 1988Use of nicotine gum was substantially different between the relevant arms of the trial, and the intervention condition was also a test of the impact of training.
Wolfenden 2005Only 3 month follow-up. Test of multifaceted intervention including offer of NRT at preoperative clinics.
Yu 2006Only 12 weeks follow-up from start of treatment.

Characteristics of ongoing studies [ordered by study ID]

Humfleet 2011

Trial name or titleSmoking cessation in HIV+ clinical care settings
MethodsClinical trial evaluating smoking treatment provided in HIV clinical care settings
Participants207 HIV+ smokers, mean age 45
Interventions

Participants randomly assigned to one of 3 treatments:

(a) 6 session individual counselling treatment

(b) computer/ internet based treatment

(c) minimal contact control condition

All participants had access to 10-weeks of nicotine replacement therapy; treatment duration was 12 weeks.

Outcomes7 day PP abstinence at weeks 12, 24, 36 and 52. Biochemically confirmed with CO < 10 ppm.
Starting dateNot specified
Contact informationgaryh@lppi.ucsf.edu
NotesStudy completed but full results not yet published

Ancillary