This additional information describes in detail the effectiveness evidence and cost information on pharmacological interventions for smoking cessation. The selection of the effectiveness evidence had following steps: the literature search and selection of effectiveness evidence and quality appraisal. We chose the network meta-analysis by Shang et al. (2022) as the base of the effectiveness evidence. «Shang X, Guo K, E F, ym. Pharmacological intervent...»1
Source of the effectiveness evidence: Shang X, Guo K, E F, Deng X, Wang Y, Wang Z, Wu Y, Xu M, Yang C, Li X, Yang K. Pharmacological interventions on smoking cessation: A systematic review and network meta-analysis. Front Pharmacol. 2022 Oct 24;13:1012433. doi: 10.3389/fphar.2022.1012433.
Literature search and selection
The literature search included network meta-analyses, meta-analyses and systematic reviews of pharmacological interventions for smoking cessation. Information specialist conducted the literature searches in October 2022. The timeframe for the search was years 2018–2022. The search found 90 references. An additional hand search found one reference of network meta-analysis for pharmacological interventions on smoking cessation (Shang et al. 2022) «Shang X, Guo K, E F, ym. Pharmacological intervent...»1 which was published after the literature search. We searched for the most recent evidence by viewing only network meta-analyses published in 2022 and 2021, if satisfactory number of comprehensive studies were found. A total of six network meta-analyses were published in 2022 and 2021 «Description of the network meta-analyses of pharmacological interventions for smoking cessation published in 2021 and 2022...»1.
| Citation | Research aim | Number of trials, date of literature search | Outcome measures | Interventions | Comments |
|---|---|---|---|---|---|
| NRT= nicotine replacement therapy | |||||
| Guo et al. 2022 «Guo K, Wang S, Shang X, ym. The effect of Varenicl...»2 | To investigate the effect of varenicline (VAR), bupropion (BUP), and nicotine replacement therapy (NRT) on smoking cessation. | 20 RCTs. May 2021. |
The number of people who quit smoking | bupropion, nicotine replacement therapy, varenicline |
Did not include nortriptyline. |
| Thomas et al. 2022 «Thomas KH, Dalili MN, López-López JA, ym. Comparat...»3 | To determine how varenicline, bupropion, nicotine replacement therapy (NRT) and electronic cigarettes compare with respect to their clinical effectiveness and safety. |
363 RCTs. February 2019. |
Sustained abstinence, prolonged abstinence, any abstinence, 7-day point prevalence abstinence (PPA). |
bupropion, e-cigarette, NRT patch (16 hours), NRT patch (24 hours), NRT gum, NRT nasal spray, NRT month spray, NRT lozenge, NRT sublingual tablet, NRT inhalator, varenicline |
Did not include nortriptyline. |
| Mishra et al. 2021 «Mishra A, Maiti R, Mishra BR, ym. Comparative effi...»4 |
To evaluate and compare different pharmacological interventions with or without behavioural
therapy used for smoking cessation in healthy adult |
97 RCTs. September 2020. |
Biochemically confirmed (carbon monoxide or cotinine confirmed) continuous or prolonged abstinence rates at six months or 24–26 weeks | behavioural therapy, bupropion, clonidine, lobeline, naltrexone (opioid receptor antagonist), nicotine replacement therapy, other antidepressants (nortriptyline, duloxetine, MAO-B inhibitor), partial agonists at nicotine receptor (NRA) includes varenicline, dianicline or cytisine. |
Comprehensive, includes all selected interventions. Still, varenicline was evaluated together with other partial agonists at nicotine receptors (NRA) namely dianicline and cytisine. Additional analysis evaluated nicotine replacement therapies (NRT) by type. |
| Chan et al. 2021 «Chan GCK, Stjepanović D, Lim C, ym. Gateway...»5 | To compare the effectiveness of nicotine e-cigarettes for smoking cessation with licensed nicotine replacement therapies and nicotine-free based control conditions by using network meta-analysis. | 7 RCTs. April 2020 | Smoking abstinence at the end of the study (unless the study specified a follow-up time as the primary measurement time point. |
nicotine e-cigarettes, nicotine replacement therapy (e.g., nicotine patches, nicotine gums, etc), nicotine-free e- cigarettes. |
Did not include selected interventions. |
| Thomas et al. 2021 «Thomas KH, Dalili MN, López-López JA, ym. Smoking ...»6 | To determine the clinical effectiveness, safety and cost-effectiveness of smoking
cessation medicines and e-cigarettes. |
363 RCTs. February 2019. | Sustained (or continuous) abstinence, prolonged abstinence, any abstinence at 6 months, and 7-day point prevalence abstinence (PPA) |
bupropion, e-cigarette therapies, nicotine replacement therapy, varenicline. |
Did not include nortriptyline. |
| Shang et al. 2022 «Shang X, Guo K, E F, ym. Pharmacological intervent...»1 | To investigate the effects of pharmacological interventions on smoking cessation. |
159 RCTs. June 2022. | Overall abstinence rate, continuous abstinence rate, 7-point continuous abstinence rate. | bupropion, clonidine, cytisine, fluoxetine, naltrexone, nicotine replacement therapy, nortriptyline, mecamylamine, selegiline, topiramate, varenicline. | Comprehensive, includes all selected interventions. |
We selected two studies «Shang X, Guo K, E F, ym. Pharmacological intervent...»1, «Mishra A, Maiti R, Mishra BR, ym. Comparative effi...»4 for further examination of the effectiveness of pharmacological interventions. Shang et al. (2022) «Shang X, Guo K, E F, ym. Pharmacological intervent...»1 was the most recent, comprehensive, and included all selected pharmacological interventions. Mishra et al. (2021) «Mishra A, Maiti R, Mishra BR, ym. Comparative effi...»4 was also recently published, comprehensive, included all selected pharmacological interventions and behavioural intervention. However, varenicline was evaluated only together with other partial agonists at nicotine receptors (NRA) namely dianicline and cytisine. The network meta-analysis had an additional analysis to evaluate nicotine replacement therapies (NRT) by type.
Quality of the selected network meta-analyses
We evaluated the quality of the Mishra et al. (2021) «Mishra A, Maiti R, Mishra BR, ym. Comparative effi...»4 and Shang et al. (2022) «Shang X, Guo K, E F, ym. Pharmacological intervent...»1 network meta-analyses by using AMSTAR 2 «Shea BJ, Reeves BC, Wells G, ym. AMSTAR 2: a criti...»7. The results of the quality appraisal are shown in Table 2 «Critical appraisal of selected network meta-analyses by using AMSTAR 2 ...»2.
| Question | Mishra et al. 2021 «Mishra A, Maiti R, Mishra BR, ym. Comparative effi...»4 | Shang et al. 2022 «Shang X, Guo K, E F, ym. Pharmacological intervent...»1 | ||
|---|---|---|---|---|
| RoB = Risk of Bias | ||||
| Answer | Comments | Answer | Comments | |
|
Yes | Yes | ||
|
Partial Yes | No justifications for deviations from the protocol | No | No written protocol or guide cited. |
|
Yes | Yes | ||
|
Yes | Partial yes | Did not search trial/study registers | |
|
Yes | Yes | ||
|
Yes | Yes | ||
|
Partial yes | No reference list of excluded studies with justification for exclusion. Justifications for exclusions reported in the PRISMA diagram. | Partial yes | No reference list of excluded studies with justification for exclusion. Justifications for exclusions reported in the PRISMA diagram. |
|
Partial yes | Study did not describe sample sizes by trial arms. | Yes | |
|
Yes | Yes | ||
|
No | Study did not report the sources of funding of the included studies. | No | Study did not report the sources of funding of the included studies. |
|
Yes | Yes | ||
|
No | Did not include only low risk of bias RCTs or perform analyses to investigate possible impact of the RoB on summary estimates of effects | No | Did not include only low risk of bias RCTs or perform analyses to investigate possible impact of the RoB on summary estimates of effects |
|
Yes | Yes | ||
|
Yes | Yes | ||
|
No | Did not perform graphical or statistical tests for publication bias and discuss the likelihood and magnitude of impact of publication bias. | No | Did not perform graphical or statistical tests for publication bias and discuss the likelihood and magnitude of impact of publication bias. |
|
Yes | Yes | ||
| Summary of the quality | Yes n=10 Partial yes n=3 No n=3 |
Yes n=10
Partial yes n=2 No n=4 |
||
We chose the network meta-analysis by Shang et al. (2022) «Shang X, Guo K, E F, ym. Pharmacological intervent...»1 as the base of our effectiveness estimates as it was the most recent and comprehensive study by including all the selected interventions separately. Shang et al. (2022) «Shang X, Guo K, E F, ym. Pharmacological intervent...»1 included RCTs regardless the participants age and health condition to represent the effectiveness of interventions in heterogenous population.
The effectiveness evidence
Network meta-analysis by Shang et al. (2022) «Shang X, Guo K, E F, ym. Pharmacological intervent...»1 included 159 RCTs with 60 285 smokers. The characteristics of original RCTs are presented in Supplementary table 2 of Shang et al. (2022) «Shang X, Guo K, E F, ym. Pharmacological intervent...»1. Shortly, most of the trials studied normal population (104 RCTs). Total of 20 trials included smokers with alcohol dependence, 10 with mental disease, 7 with cardiovascular disease, 5 with chronic obstructive pulmonary disease, 3 with pregnancy, 2 with posttraumatic stress disorder, 2 with substance use disorder, 2 with cancer, one with AIDS, one with asthma, one with tuberculosis and one with medical disease. The most common average number of cigarettes smoked per day was over 10 in the trials.
The study reported odds ratios (OR) and 95%CI for the Current Care working group's selected interventions compared to placebo. The smoking cessation was defined overall abstinence rate which included continuous abstinence rate or point abstinence rate generally confirmed with biochemical validation based on the self-reported smoking status at 24 weeks (39 RCTs), 26 weeks (10 RCTs), 48 weeks (28 RCTs) or 53 weeks (34 RCTs). We converted the ORs to NNTs «Schünemann HJ, Vist GE, Higgins JPT, Santesso N, D...»8. Assumed comparator risk (5%) was the pooled result of the 58 RCT's minimal intervention or no intervention groups' smoking cessation in 6-months «Hartmann-Boyce J, Livingstone-Banks J, Ordóñez-Men...»9.
Costs of medicines
Costs of the prescription medicines used in smoking cessation are from drug database available at Terveysportti health portal (Duodecim Publishing Company Ltd) «https://www.terveysportti.fi/terveysportti/koti»1. Costs of the nicotine replacement therapies are from websites of pharmacies. To calculate the costs of the medicines, we used the shortest duration and the lowest dosing of the treatment. Then, we used retail prices of the cheapest product to calculate the costs. In some cases, the dose was slightly under or over the required dose level due to limited sizes of medical packages. Any other direct or indirect costs or reimbursements were not considered.