ABSTRACT
The objective of this study is to describe the general approaches to network meta-analysis that are available for quantitative data synthesis using R software. We conducted a network meta-analysis using two approaches: Bayesian and frequentist methods. The corresponding R packages were “gemtc” for the Bayesian approach and “netmeta” for the frequentist approach. In estimating a network meta-analysis model using a Bayesian framework, the “rjags” package is a common tool. “rjags” implements Markov chain Monte Carlo simulation with a graphical output. The estimated overall effect sizes, test for heterogeneity, moderator effects, and publication bias were reported using R software. The authors focus on two flexible models, Bayesian and frequentist, to determine overall effect sizes in network meta-analysis. This study focused on the practical methods of network meta-analysis rather than theoretical concepts, making the material easy to understand for Korean researchers who did not major in statistics. The authors hope that this study will help many Korean researchers to perform network meta-analyses and conduct related research more easily with R software.
Subject(s)
Bayes Theorem , Hope , Markov Chains , Population Characteristics , Publication BiasABSTRACT
The objective of this study is to describe the general approaches to network meta-analysis that are available for quantitative data synthesis using R software. We conducted a network meta-analysis using two approaches: Bayesian and frequentist methods. The corresponding R packages were “gemtc” for the Bayesian approach and “netmeta” for the frequentist approach. In estimating a network meta-analysis model using a Bayesian framework, the “rjags” package is a common tool. “rjags” implements Markov chain Monte Carlo simulation with a graphical output. The estimated overall effect sizes, test for heterogeneity, moderator effects, and publication bias were reported using R software. The authors focus on two flexible models, Bayesian and frequentist, to determine overall effect sizes in network meta-analysis. This study focused on the practical methods of network meta-analysis rather than theoretical concepts, making the material easy to understand for Korean researchers who did not major in statistics. The authors hope that this study will help many Korean researchers to perform network meta-analyses and conduct related research more easily with R software.
Subject(s)
Bayes Theorem , Hope , Markov Chains , Population Characteristics , Publication BiasABSTRACT
BACKGROUND/AIMS: Biological agents (biologics) targeting proinflammatory signaling have emerged as an important treatment option in rheumatoid arthritis (RA). Despite the clinical effectiveness of biologics for patients with RA who do not respond to ‘traditional’ disease-modifying anti-rheumatic drugs (DMARDs), there are concerns regarding their cost and long-term safety. In this study, we aimed to compare the efficacy of various biologics and traditional DMARDs in RA patients refractory to methotrexate (MTX). METHODS: Four DMARDs (hydroxychloroquine, sulfasalazine, MTX, leflunomide) and five anti-tumor necrosis factor drugs (adalimumab, etanercept, golimumab, infliximab, and certolizumab) were selected. A systematic search of published studies was performed from inception through July 2013. Randomized trials of adults with MTX-refractory RA comparing two or more of the selected medications were included. Among 7,938 titles identified, in total, 16 head-to-head trials were selected. Two reviewers independently abstracted the study data and assessed methodological quality using the Cochrane Risk of Bias. Comparative efficacy was analyzed using a Bayesian mixed treatment comparison (MTC). RESULTS: In total, 9, 4, and 11 studies were included for the outcome measures of the Health Assessment Questionnaire (HAQ), Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) < 2.6 (remission), and American College of Rheumatology (ACR) 70 response, respectively. The treatments with the highest efficacy for each outcome measure were certolizumab combined with MTX, golimumab combined with MTX, and certolizumab combined with MTX, respectively. CONCLUSIONS: Based on MTC analysis, using data from published randomized controlled trials, certolizumab and golimumab combined with MTX showed the highest efficacy in the three outcome measures (HAQ, DAS28-ESR < 2.6, and ACR 70 response) in MTX-refractory RA patients.
Subject(s)
Adult , Humans , Antirheumatic Agents , Arthritis, Rheumatoid , Bias , Biological Factors , Biological Products , Etanercept , Infliximab , Methotrexate , Necrosis , Outcome Assessment, Health Care , Rheumatology , Sulfasalazine , Treatment OutcomeABSTRACT
BACKGROUND/AIMS: Biological agents (biologics) targeting proinflammatory signaling have emerged as an important treatment option in rheumatoid arthritis (RA). Despite the clinical effectiveness of biologics for patients with RA who do not respond to ‘traditional’ disease-modifying anti-rheumatic drugs (DMARDs), there are concerns regarding their cost and long-term safety. In this study, we aimed to compare the efficacy of various biologics and traditional DMARDs in RA patients refractory to methotrexate (MTX). METHODS: Four DMARDs (hydroxychloroquine, sulfasalazine, MTX, leflunomide) and five anti-tumor necrosis factor drugs (adalimumab, etanercept, golimumab, infliximab, and certolizumab) were selected. A systematic search of published studies was performed from inception through July 2013. Randomized trials of adults with MTX-refractory RA comparing two or more of the selected medications were included. Among 7,938 titles identified, in total, 16 head-to-head trials were selected. Two reviewers independently abstracted the study data and assessed methodological quality using the Cochrane Risk of Bias. Comparative efficacy was analyzed using a Bayesian mixed treatment comparison (MTC). RESULTS: In total, 9, 4, and 11 studies were included for the outcome measures of the Health Assessment Questionnaire (HAQ), Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) < 2.6 (remission), and American College of Rheumatology (ACR) 70 response, respectively. The treatments with the highest efficacy for each outcome measure were certolizumab combined with MTX, golimumab combined with MTX, and certolizumab combined with MTX, respectively. CONCLUSIONS: Based on MTC analysis, using data from published randomized controlled trials, certolizumab and golimumab combined with MTX showed the highest efficacy in the three outcome measures (HAQ, DAS28-ESR < 2.6, and ACR 70 response) in MTX-refractory RA patients.
Subject(s)
Adult , Humans , Antirheumatic Agents , Arthritis, Rheumatoid , Bias , Biological Factors , Biological Products , Etanercept , Infliximab , Methotrexate , Necrosis , Outcome Assessment, Health Care , Rheumatology , Sulfasalazine , Treatment OutcomeABSTRACT
This review aimed to arrange the concepts of a network meta-analysis (NMA) and to demonstrate the analytical process of NMA using Stata software under frequentist framework. The NMA tries to synthesize evidences for a decision making by evaluating the comparative effectiveness of more than two alternative interventions for the same condition. Before conducting a NMA, 3 major assumptions—similarity, transitivity, and consistency—should be checked. The statistical analysis consists of 5 steps. The first step is to draw a network geometry to provide an overview of the network relationship. The second step checks the assumption of consistency. The third step is to make the network forest plot or interval plot in order to illustrate the summary size of comparative effectiveness among various interventions. The fourth step calculates cumulative rankings for identifying superiority among interventions. The last step evaluates publication bias or effect modifiers for a valid inference from results. The synthesized evidences through five steps would be very useful to evidence-based decision-making in healthcare. Thus, NMA should be activated in order to guarantee the quality of healthcare system.
Subject(s)
Decision Making , Delivery of Health Care , Forests , Publication Bias , Quality of Health Care , Treatment OutcomeABSTRACT
This review aimed to arrange the concepts of a network meta-analysis (NMA) and to demonstrate the analytical process of NMA using Stata software under frequentist framework. The NMA tries to synthesize evidences for a decision making by evaluating the comparative effectiveness of more than two alternative interventions for the same condition. Before conducting a NMA, 3 major assumptions—similarity, transitivity, and consistency—should be checked. The statistical analysis consists of 5 steps. The first step is to draw a network geometry to provide an overview of the network relationship. The second step checks the assumption of consistency. The third step is to make the network forest plot or interval plot in order to illustrate the summary size of comparative effectiveness among various interventions. The fourth step calculates cumulative rankings for identifying superiority among interventions. The last step evaluates publication bias or effect modifiers for a valid inference from results. The synthesized evidences through five steps would be very useful to evidence-based decision-making in healthcare. Thus, NMA should be activated in order to guarantee the quality of healthcare system.
Subject(s)
Decision Making , Delivery of Health Care , Forests , Publication Bias , Quality of Health Care , Treatment OutcomeABSTRACT
OBJECTIVE:To explore the basic principles,advantages and application prospects of Bayesian mixed treatment comparison (MTC),and provide theoretic support for making reasonable decisions of pharmacoeconomics. METHODS:The prob-lems existing in model and method that had been used in the study of pharmacoeconomics as starting point,literature research was used to sort out the domestic development and applications of MTC and study its application and development prospect. RESULTS &CONCLUSIONS:The evaluation methods of pharmacoeconomics play an important role in selection of essential medicines,medi-care insurance directory medicines,basic health and basic public health programs,the results directly affect the total effective rate of medical resources’configuration. The current research models cannot effectively solve the problem,for example,decision tree model is difficult to make evaluation of long-term treatment;Markov model and the use of multiple attribute utility theory are restricted by the model parameters;discrete event simulation is limited because it depends on the epidemiological study and clinical trial. MTC, an extension approach of the traditional Meta-analysis,is an effective new method developed recently to analyze and compare the di-rect or indirect evidence of several different clinical treatment factors in order to make a comprehensive evaluation of the various inter-ventions in the absence of evidence support. So the MTC can make up for the limitation of current evaluation methods.
ABSTRACT
OBJECTIVE: Second-generation antipsychotics have been repeatedly shown to be superior to placebo. However, the comparative efficacy among these drugs has not been systematically evaluated. In this study, we used Mixed Treatment Comparison (MTC) procedures to elucidate the comparative efficacy and tolerability of second-generation antipsychotics. METHODS: Seven antipsychotics were selected based on the availability of the relevant data. Data were gathered from a series of review article published by the Cochrane Collaboration. Six outcome measures were analyzed: 1) percentage of no clinically important response as defined by the original authors, 2) PANSS total score change from baseline to endpoint, 3) percentage of akathisia, 4) percentage of antiparkinson medication use, 5) percentage of total body weight increase more than 7%, and 6) percentage of drop-out due to any reasons. RESULTS: All the second-generation antipsychotics included in this study showed fairly similar efficacy but widely different tolerability. In terms of efficacy, amisulpride, clozapine and olanzapine were ranked higher than aripiprazole, quetiapine and ziprasidone. Clozapine and olanzapine were superior in terms of akathisia and extrapyramidal symptom risk, but, far more prone to induce clinically important weight gain. CONCLUSION: Using MTC methodology, we could line up the second generation antipsychotics according to their hierarchical superiority in terms of efficacy and tolerability. Though the wide overlap among the confidence intervals and the inconsistency between the direct and indirect comparison results may limit the validity of these results, it may still allow the important insights into the relative merits of the available drugs.