Fragility index of network meta-analysis with application to smoking cessation data.
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ABSTRACT: Background and objectives
The network meta-analysis (NMA) is frequently used to synthesize evidence for multiple treatment comparisons, but its complexity may affect the robustness (or fragility) of the results. The fragility index (FI) is recently proposed to assess the fragility of the results from clinical studies and from pairwise meta-analyses. We extend the FI to NMAs with binary outcomes.Methods
We define the FI for each treatment comparison in NMAs. It quantifies the minimal number of events necessary to be modified for altering the comparison's statistical significance. We introduce an algorithm to derive the FI and visualizations of the process. A worked example of smoking cessation data is used to illustrate the proposed methods.Results
Some treatment comparisons had small FIs; their significance (or nonsignificance) could be altered by modifying a few events' status. They were related to various factors, such as P-values, event counts, and sample sizes, in the original NMA. After modifying event status, treatment ranking measures were also changed to different extents.Conclusion
Many NMAs include insufficiently compared treatments, small event counts, or small sample sizes; their results are potentially fragile. The FI offers a useful tool to evaluate treatment comparisons' robustness and reliability.
SUBMITTER: Xing A
PROVIDER: S-EPMC7669670 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionConverging clinical and biological evidence suggest sex is an important factor when selecting a pharmacological intervention for smoking cessation. The current investigation used network meta-analyses to estimate sex differences in the comparative efficacy of transdermal nicotine (TN), varenicline, and sustained release (SR) bupropion for smoking cessation.MethodsSystematically searched previously published reviews and databases (Medline, PsycINFO, Embase) of randomized, double-blind, placebo-controlled trials of bupropion-SR, TN, and varenicline for cigarette smoking cessation in primary care/general community samples were included.ResultsThirty-two studies met all criteria and 28 (88%) were included in the final analyses, representing 14 389 smokers (51% female). Results of the full sample (women and men combined) mirrored those from a Cochrane Tobacco Addiction Group network meta-analysis of smoking cessation pharmacotherapy, showing VAR>TN=BUP. All medications improved quit rates over placebo for both women and men. Relative to placebo, varenicline efficacy was similar for women and men. Significant sex differences were evident when comparing varenicline versus TN and varenicline versus bupropion. For women, varenicline was more efficacious than TN (RR = 1.41; 95% CI = 1.12,1.76) and bupropion (RR = 1.38; 95% CI = 1.08,1.77). For men, outcomes for those treated with TN and bupropion were similar to those treated with varenicline. There were no differences in efficacy when comparing bupropion versus TN.ConclusionsThe advantage of varenicline over bupropion SR and TN is greater for women than men. Clinicians should strongly consider varenicline as the first option treatment for women. Among men, the advantage of varenicline over TN or bupropion is less clear.ImplicationsThis study provides information for the sex-informed treatment of nicotine addiction among cigarette smokers. Relative to placebo, women and men achieved similar outcomes when treated with varenicline; however the advantages of varenicline over transdermal patch and bupropion were greater for women compared to men.
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Project description:Traditional mediation analysis assumes that a study population is homogeneous and the mediation effect is constant over time, which may not hold in some applications. Motivated by smoking cessation data, we propose a latent class dynamic mediation model that explicitly accounts for the fact that the study population may consist of different subgroups and the mediation effect may vary over time. We use a proportional odds model to accommodate the subject heterogeneities and identify latent subgroups. Conditional on the subgroups, we employ a Bayesian hierarchical nonparametric time-varying coefficient model to capture the time-varying mediation process, while allowing each subgroup to have its individual dynamic mediation process. A simulation study shows that the proposed method has good performance in estimating the mediation effect. We illustrate the proposed methodology by applying it to analyze smoking cessation data.
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Project description:BACKGROUND: Smoking remains the leading preventable cause of premature deaths. Several pharmacological interventions now exist to aid smokers in cessation. These include Nicotine Replacement Therapy [NRT], bupropion, and varenicline. We aimed to assess their relative efficacy in smoking cessation by conducting a systematic review and meta-analysis. METHODS: We searched 10 electronic medical databases (inception to Sept. 2006) and bibliographies of published reviews. We selected randomized controlled trials [RCTs] evaluating interventions for smoking cessation at 1 year, through chemical confirmation. Our primary endpoint was smoking cessation at 1 year. Secondary endpoints included short-term smoking cessation (approximately 3 months) and adverse events. We conducted random-effects meta-analysis and meta-regression. We compared treatment effects across interventions using head-to-head trials and when these did not exist, we calculated indirect comparisons. RESULTS: We identified 70 trials of NRT versus control at 1 year, Odds Ratio [OR] 1.71, 95% Confidence Interval [CI], 1.55-1.88, P =< 0.0001). This was consistent when examining all placebo-controlled trials (49 RCTs, OR 1.78, 95% CI, 1.60-1.99), NRT gum (OR 1.60, 95% CI, 1.37-1.86) or patch (OR 1.63, 95% CI, 1.41-1.89). NRT also reduced smoking at 3 months (OR 1.98, 95% CI, 1.77-2.21). Bupropion trials were superior to controls at 1 year (12 RCTs, OR1.56, 95% CI, 1.10-2.21, P = 0.01) and at 3 months (OR 2.13, 95% CI, 1.72-2.64). Two RCTs evaluated the superiority of bupropion versus NRT at 1 year (OR 1.14, 95% CI, 0.20-6.42). Varenicline was superior to placebo at 1 year (4 RCTs, OR 2.96, 95% CI, 2.12-4.12, P =< 0.0001) and also at approximately 3 months (OR 3.75, 95% CI, 2.65-5.30). Three RCTs evaluated the effectiveness of varenicline versus bupropion at 1 year (OR 1.58, 95% CI, 1.22-2.05) and at approximately 3 months (OR 1.61, 95% CI, 1.16-2.21). Using indirect comparisons, varenicline was superior to NRT when compared to placebo controls (OR 1.66, 95% CI 1.17-2.36, P = 0.004) or to all controls at 1 year (OR 1.73, 95% CI 1.22-2.45, P = 0.001). This was also the case for 3-month data. Adverse events were not systematically different across studies. CONCLUSION: NRT, bupropion and varenicline all provide therapeutic effects in assisting with smoking cessation. Direct and indirect comparisons identify a hierarchy of effectiveness.
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Project description:IntroductionThis systematic review of randomized controlled trials (RCTs) evaluated the efficacy and safety of electronic cigarettes (e-cigarettes, ENDS) in helping people who smoke to achieve abstinence compared with electronic non-nicotine delivery systems (ENNDS, no nicotine) or any smoking cessation comparator treatment or combination of treatments at 24-26 weeks and at 52 weeks.MethodsSystematic review techniques involved searches of three databases in February 2020 with update searches run on 14 May 2021, two-person independent screening, two-person independent assessment of bias, formal extraction of data with verification by a second person, a feasibility assessment to decide if meta-analysis was appropriate, and network meta-analysis (NMA) of data at 24-26 weeks. Data at 52 weeks were narratively summarized.ResultsTen RCTs met the inclusion criteria, eight for efficacy and ten for safety. Eight of the nine RCTs were assessed as at high risk of bias. The sample sizes of the RCTs were 30-2012. Using nicotine replacement therapy (NRT) as the reference treatment, the incidences of smoking cessation at 24-26 weeks were comparable between ENDS and NRT groups (RR=1.17; 95% CrI: 0.66-1.86). Three sensitivity analyses were carried out indicating the main findings for 24-26 weeks were robust to assumptions. The findings at 52 weeks were inconclusive.ConclusionsThis systematic review and NMA indicates that there is no clear evidence of a difference in effect between nicotine containing e-cigarettes and NRT on incidences of smoking cessation at 24-26 weeks, and substantial uncertainty remains.
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Project description:BackgroundMany placebo-controlled trials have demonstrated the efficacy of individual pharmacotherapies approved for smoking cessation. However, few direct or indirect comparisons of such interventions have been conducted. We performed a meta-analysis to compare the treatment effects of 7 approved pharmacologic interventions for smoking cessation.MethodsWe searched the US Centers for Disease Control and Prevention's Tobacco Information and Prevention database as well as MEDLINE, EMBASE and the Cochrane Library for published reports of placebo-controlled, double-blind randomized controlled trials of pharmacotherapies for smoking cessation. We included studies that reported biochemically validated measures of abstinence at 6 and 12 months. We used a hierarchical Bayesian random-effects model to summarize the results for each intervention.ResultsWe identified 70 published reports of 69 trials involving a total of 32 908 patients. Six of the 7 pharmacotherapies studied were found to be more efficacious than placebo: varenicline (odds ratio [OR] 2.41, 95% credible interval [CrI] 1.91-3.12), nicotine nasal spray (OR 2.37, 95% CrI 1.12-5.13), bupropion (OR 2.07, 95% CrI 1.73-2.55), transdermal nicotine (OR 2.07, 95% CrI 1.69-2.62), nicotine tablet (OR 2.06, 95% CrI 1.12-5.13) and nicotine gum (OR 1.71, 95% CrI 1.35-2.21). Similar results were obtained regardless of which measure of abstinence was used. Although the point estimate favoured nicotine inhaler over placebo (OR 2.17), these results were not conclusive because the credible interval included unity (95% CrI 0.95-5.43). When all 7 interventions were included in the same model, all were more efficacious than placebo. In our analysis of data from the varenicline trials that included bupropion control arms, we found that varenicline was superior to bupropion (OR 2.18, 95% CrI 1.09-4.08).InterpretationVarenicline, bupropion and the 5 nicotine replacement therapies were all more efficacious than placebo at promoting smoking abstinence at 6 and 12 months.
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Project description:BackgroundRapid advancements in eHealth and mobile health (mHealth) technologies have driven researchers to design and evaluate numerous technology-based interventions to promote smoking cessation. The evolving nature of cessation interventions emphasizes a strong need for knowledge synthesis.ObjectiveThis systematic review and meta-analysis aimed to summarize recent evidence from randomized controlled trials regarding the effectiveness of eHealth-based smoking cessation interventions in promoting abstinence and assess nonabstinence outcome indicators, such as cigarette consumption and user satisfaction, via narrative synthesis.MethodsWe searched for studies published in English between 2017 and June 30, 2022, in 4 databases: PubMed (including MEDLINE), PsycINFO, Embase, and Cochrane Library. Two independent reviewers performed study screening, data extraction, and quality assessment based on the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework. We pooled comparable studies based on the population, follow-up time, intervention, and control characteristics. Two researchers performed an independent meta-analysis on smoking abstinence using the Sidik-Jonkman random-effects model and log risk ratio (RR) as the effect measurement. For studies not included in the meta-analysis, the outcomes were narratively synthesized.ResultsA total of 464 studies were identified through an initial database search after removing duplicates. Following screening and full-text assessments, we deemed 39 studies (n=37,341 participants) eligible for this review. Of these, 28 studies were shortlisted for meta-analysis. According to the meta-analysis, SMS or app text messaging can significantly increase both short-term (3 months) abstinence (log RR=0.50, 95% CI 0.25-0.75; I2=0.72%) and long-term (6 months) abstinence (log RR=0.77, 95% CI 0.49-1.04; I2=8.65%), relative to minimal cessation support. The frequency of texting did not significantly influence treatment outcomes. mHealth apps may significantly increase abstinence in the short term (log RR=0.76, 95% CI 0.09-1.42; I2=88.02%) but not in the long term (log RR=0.15, 95% CI -0.18 to 0.48; I2=80.06%), in contrast to less intensive cessation support. In addition, personalized or interactive interventions showed a moderate increase in cessation for both the short term (log RR=0.62, 95% CI 0.30-0.94; I2=66.50%) and long term (log RR=0.28, 95% CI 0.04-0.53; I2=73.42%). In contrast, studies without any personalized or interactive features had no significant impact. Finally, the treatment effect was similar between trials that used biochemically verified or self-reported abstinence. Among studies reporting outcomes besides abstinence (n=20), a total of 11 studies reported significantly improved nonabstinence outcomes in cigarette consumption (3/14, 21%) or user satisfaction (8/19, 42%).ConclusionsOur review of 39 randomized controlled trials found that recent eHealth interventions might promote smoking cessation, with mHealth being the dominant approach. Despite their success, the effectiveness of such interventions may diminish with time. The design of more personalized interventions could potentially benefit future studies.Trial registrationPROSPERO CRD42022347104; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=347104.
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Project description:IntroductionWomen have lower rates of quitting than men with both bupropion and nicotine replacement. It is unknown whether varenicline demonstrates differential efficacy for men and women. The purpose of this study was to conduct the first comprehensive meta-analysis of clinical trial data examining sex differences in the efficacy of varenicline for smoking cessation.MethodsSearching MEDLINE, EMBASE, and PsychINFO, 17 of 43 clinical trials of varenicline for smoking cessation published through December 31, 2014 were low-bias randomized double-blind placebo-controlled trials. Data (n = 6710 smokers, 34% female, n = 16 studies, 96% of available data) was analyzed with Metafor program in R. Outcome endpoints were 7-day point-prevalence (PP) and continuous-abstinence (CA) at week 12 (end of treatment), week 24 (6-month follow-up), and week 52 (12-month follow-up).ResultsUsing placebo, women were less likely than men to quit (PP-12, CA-24; P < .05 for sex). Using varenicline, similar rates of abstinence for men and women were demonstrated for all six outcomes (eg, PP-12 abstinence rates were 53% in both women and men). Varenicline versus placebo outcomes demonstrated that varenicline was more effective for women for short and intermediate outcomes (PP-12, CA-12, CA-24; P < .05 sex × medication interaction). For end-of-treatment PP, varenicline was 46% more effective for women. For continuous abstinence, varenicline was 34% (CA-12) and 31% (CA-24) more effective for women.ConclusionsUnlike other smoking cessation medications, varenicline demonstrated greater efficacy among women smokers for short and immediate-term outcomes and equal efficacy for 1-year outcomes. Varenicline may be particularly useful for reducing the sex disparity typically seen in rates of smoking cessation.ImplicationsVarenicline is currently the most effective FDA-approved smoking cessation medication and this is the first demonstration that women compared with men have a preferred therapeutic response for a smoking cessation medication when considering short-term outcomes. Importantly, this is also the first demonstration that women have similar rates of quitting to men when considering longer-term, 1-year outcomes.
| S-EPMC5942618 | biostudies-literature
Project description:ObjectivesThis meta-analysis sought to evaluate the efficacy of opioid antagonists in promoting long-term smoking cessation. Post-treatment abstinence was examined as a secondary outcome and effects on withdrawal symptoms, craving and reduced consumption were also explored.DesignThe search strategy for this meta-analysis included clinical trials (published and unpublished data) in the Cochrane Tobacco Addiction Group Specialized Register and MEDLINE.ParticipantsAdult smokers.InterventionsWe included randomised trials comparing opioid antagonists to placebo or an alternative therapy for smoking cessation and reported data on abstinence for a minimum of 6 months.Primary and secondary outcome measuresOutcomes included smoking abstinence at long-term follow-up (primary); abstinence at end of treatment (secondary); and effects on withdrawal, craving and smoking consumption (exploratory).Results8 trials with a total of 1213 participants were included. Half the trials examined the benefit of adding naltrexone versus placebo to nicotine replacement therapy (NRT). There was no significant difference between naltrexone and placebo alone (relative risk (RR) 1.00; 95% CI 0.66 to 1.51) or as an adjunct to NRT (RR 0.95; 95% CI 0.70 to 1.30), with an overall pooled estimate of RR 0.97; 95% CI 0.76 to 1.24. Findings for naltrexone effects on withdrawal, craving and reduced smoking were equivocal.ConclusionsThe findings indicate no beneficial effect of naltrexone alone or as an adjunct to NRT on short-term or long-term smoking abstinence. While further trials may narrow the confidence limits, they are unlikely to appreciably alter the conclusion.
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