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Study Characteristics Influence the Efficacy of Substance Abuse Treatments: A Meta-analysis of Medications for Smoking Cessation.

ABSTRACT: BACKGROUND:Understanding study characteristics' influence on treatment efficacy could improve interpretation of trials' outcomes. We examined study characteristics as predictors of outcomes in clinical trials of medications for tobacco use. METHODS:We obtained and analyzed data on 44 trials of nicotine gum, 37 trials of nicotine patch, 27 trials of varenicline, and 43 trials of bupropion from Cochrane reviews. We extracted and analyzed data for 15 study characteristics, odds ratios (ORs), and percent abstinent in control and medication conditions. We used general linear models to determine which study characteristics explained the variability among outcomes after controlling for medication characteristics. RESULTS:Study characteristics accounted for 12% of the variance in odds ratios among patch trials, 16% among gum trials, 16% among varenicline trials, and 34% among bupropion trials above and beyond medication characteristics. Patch and gum trials with industry funding had larger odds ratios than those without. Among patch trials, this appeared to be due to less abstinence in industry-funded trials' control conditions. Bupropion trials published earlier had larger odds ratios, which appeared to be due to less abstinence in control conditions. The reason for study characteristics' influence on varenicline trials was unclear. DISCUSSION:Study characteristics influenced the assessment of treatment efficacy above and beyond medication characteristics in smoking cessation trials. Our findings that study characteristics are associated with higher or lower efficacy does not suggest that the effect size under one versus another condition is the more valid outcome. Future studies are needed to determine which study characteristics reliably influence efficacy because this would help investigators and clinicians interpret trials. IMPLICATIONS:Study characteristics influenced the estimates of treatment efficacy but individual characteristics' influence on efficacy appeared to differ among different medications for smoking cessation. We encourage researchers to report study characteristics to improve interpretation of findings and systematic reviews, and to account for nontreatment-related variables to better estimate the efficacy of treatments.

SUBMITTER: Klemperer EM

PROVIDER: S-EPMC7297102 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Study Characteristics Influence the Efficacy of Substance Abuse Treatments: A Meta-analysis of Medications for Smoking Cessation.

Klemperer Elias M EM Hughes John R JR Naud Shelly S

Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco 20200301 3

<h4>Background</h4>Understanding study characteristics' influence on treatment efficacy could improve interpretation of trials' outcomes. We examined study characteristics as predictors of outcomes in clinical trials of medications for tobacco use.<h4>Methods</h4>We obtained and analyzed data on 44 trials of nicotine gum, 37 trials of nicotine patch, 27 trials of varenicline, and 43 trials of bupropion from Cochrane reviews. We extracted and analyzed data for 15 study characteristics, odds ratio ...[more]

PMID: 30380134

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Project description:AIMS:To assess (1) how far the efficacies of front-line smoking cessation pharmacotherapies vary as a function of smoker characteristics and (2) associations between these characteristics and success of smoking cessation attempts. DESIGN:Prospective correlational study in the context of a double-blind randomized trial. The outcome was regressed individually onto each covariate after adjusting for treatment, and then a forward stepwise model constructed. Treatment moderator effects of covariates were tested by treatment × covariate interactions. SETTING:Health service facilities in multiple countries. PARTICIPANTS:Data came from 8120 smokers willing to make a quit attempt, randomized to varenicline, bupropion, nicotine replacement therapy (NRT) or placebo in Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES) between 30 November 2011 and 13 January 2015. MEASUREMENTS:Smoker characteristics measured at baseline were country, psychiatric history, sex, age, body mass index (BMI), ethnic group, life-time suicidal ideation/behaviour, anxiety, depression, aggression, psychotropic medication, history of alcohol/substance use disorder, age of starting smoking, cigarette dependence [Fagerström Test for Cigarette Dependence (FTCD)] and prior use of study medicines. Outcome was biochemically confirmed continuous abstinence at weeks 9-24 from start of treatment. FINDINGS:No statistically significant treatment × covariate interactions were found. Odds of success were associated independently positively with age [odds ratio (OR) = 1.01; 95% confidence interval (CI) = 1.00, 1.01], BMI (1.01; 95% CI = 1.00, 1.02) and age of starting smoking (1.03; 95% CI = 1.02, 1.04). Odds were associated independently negatively with US (versus non-US) study site (0.53; 95% CI = 0.46, 0.61), black (versus white) ethnic group (0.57; 95% CI = 0.45, 0.72), mood disorder (0.85; 95% CI = 0.73, 0.99), anxiety disorder (0.71; 95% CI = 0.55, 0.90) and psychotic disorder (0.73; 95% CI = 0.50, 1.07), taking psychotropic medication (0.81; 95% CI = 0.68, 0.95), FTCD (0.89; 95% CI = 0.87, 0.92) and previous use of NRT (0.78; 95% CI = 0.67, 0.91). CONCLUSIONS:While a range of smoker characteristics-including psychiatric history, cigarette dependence and prior use of nicotine replacement therapy (NRT)-are associated with lower cessation rates, they do not substantially influence the efficacy of varenicline, bupropion or NRT.

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.

Project description:BACKGROUND: Two treatments for smoking cessation--varenicline and bupropion--carry Boxed Warnings from the U.S. Food and Drug Administration (FDA) about suicidal/self-injurious behavior and depression. However, some epidemiological studies report an increased risk in smoking or smoking cessation independent of treatment, and differences between drugs are unknown. METHODOLOGY: From the FDA's Adverse Event Reporting System (AERS) database from 1998 through September 2010 we selected domestic, serious case reports for varenicline (n = 9,575), bupropion for smoking cessation (n = 1,751), and nicotine replacement products (n = 1,917). A composite endpoint of suicidal/self-injurious behavior or depression was defined as a case with one or more Preferred Terms in Standardized MedDRA Query (SMQ) for those adverse effects. The main outcome measure was the ratio of reported suicide/self-injury or depression cases for each drug compared to all other serious events for that drug. RESULTS: Overall we identified 3,249 reported cases of suicidal/self-injurious behavior or depression, 2,925 (90%) for varenicline, 229 (7%) for bupropion, and 95 (3%) for nicotine replacement. Compared to nicotine replacement, the disproportionality results (OR (95% CI)) were varenicline 8.4 (6.8-10.4), and bupropion 2.9 (2.3-3.7). The disproportionality persisted after excluding reports indicating concomitant therapy with any of 58 drugs with suicidal behavior warnings or precautions in the prescribing information. An additional antibiotic comparison group showed that adverse event reports of suicidal/self-injurious behavior or depression were otherwise rare in a healthy population receiving short-term drug treatment. CONCLUSIONS: Varenicline shows a substantial, statistically significant increased risk of reported depression and suicidal/self-injurious behavior. Bupropion for smoking cessation had smaller increased risks. The findings for varenicline, combined with other problems with its safety profile, render it unsuitable for first-line use in smoking cessation.

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.

Project description:BACKGROUND AND AIMS:Although smoking cessation medications have shown effectiveness in increasing abstinence in randomized controlled trials (RCTs), it is unclear to what extent benefits persist over time. This paper assesses whether the benefits of smoking cessation medications decline over the first year. METHODS:We selected studies from three systematic reviews published by the Cochrane Collaboration. RCTs of first-line smoking cessation medications, with 6- and 12-month follow-up, were eligible for inclusion. Meta-analysis was used to synthesize information on sustained abstinence (SA) at 6 versus 12 months and 3 versus 6 months, using the risk difference (RD) ('net benefit') between intervention and control group quit rates, the relative risk (RR) and the odds ratio (OR). RESULTS:Sixty-one studies (27?647 participants) were included. Fewer than 40% of intervention group participants were sustained abstinent at 3 months (bupropion: 37.1%; nicotine replacement therapy (NRT): 34.8%; varenicline: 39.3%); approximately a quarter were sustained abstinent at 6 months (bupropion: 25.9%; NRT: 26.6%; varenicline: 25.4%), and approximately a fifth were sustained abstinent at 12 months (bupropion: 19.9%; NRT: 19.8%%; varenicline: 18.7%). There was only a small decline in RR (3 months: 1.95 [95% confidence interval (CI) = 1.74-2.18, P < 0.0001]; 6 months: 1.87 (95% CI = 1.67-2.08 P < 0.0001); 12 months: 1.75 (95% CI = 1.56-1.95, P < 0.0001) between intervention and control groups over time, but a substantial decline in net benefit [3 months: RD = 17.3% (14.5-20.1%); 6 months: RD = 11.8% (10.0-13.7%); 12 months: RD = 8.2% (6.8-9.6%)]. The decline in net benefit was statistically significant between 3 and 6 [RD = 4.95% (95% CI = 3.49-6.41%), P < 0.0001] and 6 and 12 months [RD = 3.00% (95% CI = 2.36%-3.64%), P < 0.0001)] for medications combined and individual medications. CONCLUSIONS:The proportion of smokers who use smoking cessation medications who benefit from doing so decreases during the course of the first year, but a net benefit still remains at 12 months.

Dataset Information

Study Characteristics Influence the Efficacy of Substance Abuse Treatments: A Meta-analysis of Medications for Smoking Cessation.

Publications

Study Characteristics Influence the Efficacy of Substance Abuse Treatments: A Meta-analysis of Medications for Smoking Cessation.

Similar Datasets

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