Dataset Information

Network meta-analysis of randomized clinical trials: reporting the proper summaries.

ABSTRACT: In the absence of sufficient data directly comparing multiple treatments, indirect comparisons using network meta-analyses (NMAs) can provide useful information. Under current contrast-based (CB) methods for binary outcomes, the patient-centered measures including the treatment-specific event rates and risk differences (RDs) are not provided, which may create some unnecessary obstacles for patients to comprehensively trade-off efficacy and safety measures.We aim to develop NMA to accurately estimate the treatment-specific event rates.A Bayesian hierarchical model is developed to illustrate how treatment-specific event rates, RDs, and risk ratios (RRs) can be estimated. We first compare our approach to alternative methods using two hypothetical NMAs assuming a fixed RR or RD, and then use two published NMAs to illustrate the improved reporting.In the hypothetical NMAs, our approach outperforms current CB NMA methods in terms of bias. In the two published NMAs, noticeable differences are observed in the magnitude of relative treatment effects and several pairwise statistical significance tests from previous report.First, to facilitate the estimation, each study is assumed to hypothetically compare all treatments, with unstudied arms being missing at random. It is plausible that investigators may have selected treatment arms on purpose based on the results of previous trials, which may lead to 'nonignorable missingness' and potentially bias our estimates. Second, we have not considered methods to identify and account for potential inconsistency between direct and indirect comparisons.The proposed NMA method can accurately estimate treatment-specific event rates, RDs, and RRs and is recommended.

SUBMITTER: Zhang J

PROVIDER: S-EPMC3972291 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Network meta-analysis of randomized clinical trials: reporting the proper summaries.

Zhang Jing J Carlin Bradley P BP Neaton James D JD Soon Guoxing G GG Nie Lei L Kane Robert R Virnig Beth A BA Chu Haitao H

Clinical trials (London, England) 20131003 2

<h4>Background</h4>In the absence of sufficient data directly comparing multiple treatments, indirect comparisons using network meta-analyses (NMAs) can provide useful information. Under current contrast-based (CB) methods for binary outcomes, the patient-centered measures including the treatment-specific event rates and risk differences (RDs) are not provided, which may create some unnecessary obstacles for patients to comprehensively trade-off efficacy and safety measures.<h4>Purpose</h4>We ai ...[more]

PMID: 24096635

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Project description:AIMS:Several antihypertensive drugs are used in the treatment of severe hypertension in pregnancy. The present study is a network meta-analysis comparing the efficacy and safety of these drugs. METHODS:Electronic databases were searched for randomized clinical trials comparing drugs used in the treatment of severe hypertension in pregnancy. The number of women achieving the target blood pressure (BP) was the primary outcome. Doses required and time taken for achieving the target BP, failure rate, and incidences of maternal tachycardia, palpitation, hypotension, headache, and neonatal death and stillbirth were the secondary outcomes. Mixed treatment comparison pooled estimates were generated using a random-effects model. Odds ratios for the categorical and mean difference for the numerical outcomes were the effect estimates. RESULTS:Fifty-one studies were included in the systematic review and 46 in the meta-analysis. No significant differences in the number of patients achieving target BP was observed between any of the drugs. Diazoxide [-15 (-20.6, -9.4)], nicardipine [-11.8 (-22.3, -1.2)], nifedipine/celastrol [-19.3 (-27.4, -11.1)], nifedipine/vitamin D [-17.1 (-25.7, -9.7)], nifedipine/resveratrol [-13.9 (-22.6, -5.2)] and glyceryl trinitrate [-33.8 (-36.7, -31)] were observed to achieve the target BP (in minutes) more rapidly than hydralazine. Nifedipine required fewer doses than hydralazine for achieving the target BP. Glyceryl trinitrate and labetalol were associated with fewer incidences of tachycardia and palpitation respectively than hydralazine. Trial sequential analysis concluded adequate evidence for hydralazine and nifedipine compared with labetalol. Moderate quality of evidence was observed for direct comparison estimate between labetalol and hydralazine but was either low or very low for other comparisons. CONCLUSION:The present evidence suggests similar efficacy between nifedipine, hydralazine and labetalol in the treatment of severe hypertension in pregnancy. Subtle differences may exist in their safety profile. The evidence is inadequate for other drugs.

Project description:BackgroundPulmonary arterial hypertension (PAH) is a devastating disease and ultimately leads to right heart failure and premature death. A total of four classical targeted drugs, prostanoids, endothelin receptor antagonists (ERAs), phosphodiesterase 5 inhibitors (PDE-5Is), and soluble guanylate cyclase stimulator (sGCS), have been proved to improve exercise capacity and hemodynamics compared to placebo; however, direct head-to-head comparisons of these drugs are lacking. This network meta-analysis was conducted to comprehensively compare the efficacy of these targeted drugs for PAH.MethodsMedline, the Cochrane Library, and other Internet sources were searched for randomized clinical trials exploring the efficacy of targeted drugs for patients with PAH. The primary effective end point of this network meta-analysis was a 6-minute walk distance (6MWD).ResultsThirty-two eligible trials including 6,758 patients were identified. There was a statistically significant improvement in 6MWD, mean pulmonary arterial pressure, pulmonary vascular resistance, and clinical worsening events associated with each of the four targeted drugs compared with placebo. Combination therapy improved 6MWD by 20.94 m (95% confidence interval [CI]: 6.94, 34.94; P=0.003) vs prostanoids, and 16.94 m (95% CI: 4.41, 29.47; P=0.008) vs ERAs. PDE-5Is improved 6MWD by 17.28 m (95% CI: 1.91, 32.65; P=0.028) vs prostanoids, with a similar result with combination therapy. In addition, combination therapy reduced mean pulmonary artery pressure by 3.97 mmHg (95% CI: -6.06, -1.88; P<0.001) vs prostanoids, 8.24 mmHg (95% CI: -10.71, -5.76; P<0.001) vs ERAs, 3.38 mmHg (95% CI: -6.30, -0.47; P=0.023) vs PDE-5Is, and 3.94 mmHg (95% CI: -6.99, -0.88; P=0.012) vs sGCS. There were no significant differences in all-cause mortality and severe adverse events between prostanoids, ERAs, PDE-5Is, sGCS, combination therapy, and placebo.ConclusionAll targeted drugs for PAH are associated with improved clinical outcomes, especially combination therapy. However, all these drugs seem to show less favorable effects on survival in the short-term follow-up, suggesting further clinical trials are required.

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Network meta-analysis of randomized clinical trials: reporting the proper summaries.

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Network meta-analysis of randomized clinical trials: reporting the proper summaries.

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