Consistency and inconsistency in network meta‐analysis: model estimation using multivariate meta‐regression

White, Ian R.; Barrett, Jessica; Jackson, Dan; Higgins, Julian P. T.

doi:10.1002/jrsm.1045

Cited by 851 publications

(828 citation statements)

References 29 publications

(62 reference statements)

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“…21,22 Second, we conducted network meta-analysis using a multivariate random-effects meta-regression. 23,24 Categorical outcomes were reported as risk ratio (RR), and continuous outcome (6MWD) was reported as weighted mean difference (WMD), with their corresponding 95% CIs. For categorical outcomes, an estimate for the absolute effect size was additionally obtained by multiplying the RR for each agent with the median placebo response rate for that outcome.…”

Section: Resultsmentioning

confidence: 99%

Comparative Effectiveness of Pharmacologic Interventions for Pulmonary Arterial Hypertension

Jain

Khera

Girotra

et al. 2017

Chest

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BACKGROUND:We conducted a systematic review and network meta-analysis to examine comparative efficacy and tolerability of pharmacologic interventions for pulmonary arterial hypertension (PAH).METHODS: MEDLINE, the Cochrane Register, EMBASE, CINAHL, and clinicaltrials.gov were searched (January 1, 1990 to March 3, 2016. Randomized controlled trials (RCTs) studying the approved pharmacologic agents endothelin receptor antagonists (ERA), phosphodiesterase inhibitors (PDE5i), the oral/inhaled (PO/INH) and IV/subcutaneous (SC) prostanoids, and riociguat and selexipag, alone or in combination, for pulmonary arterial hypertension (PAH) and reporting at least one efficacy outcome were selected.RESULTS: Thirty-one RCTs with 6,565 patients were selected. In network meta-analysis, when compared with a median placebo rate of 14.5%, clinical worsening was estimated at 2.8% with riociguat (risk ratio [RR], 0.19; 95% CI, 0.05-0.76); at 3.9% with ERA þ PDE5i (RR, 0.27; 95% CI, 0.14-0.52), and at 5.7% with PDE5i (RR, 0.39; 95% CI, 0.24-0.62). For improvement in functional status, when compared with 16.2% in the placebo group, improvement in at least one New York Heart Association/World Health Organization (NYHA/WHO) functional class was estimated at 81.8% with IV/SC prostanoids (RR, 5.06; 95% CI, 2.3211.04), at 28.3% with ERA þ PDE5i (RR, 1.75; 95% CI, 1.05-2.92), and at 25.2% with ERA (RR, 1.56; 95% CI, 1.22-2.00). Differences in mortality were not significant. Adverse events leading to discontinuation of therapy were highest with the PO/INH prostanoids (RR, 2.92; 95% CI, 1.68-5.06) and selexipag (RR, 2.06; 95% CI, 1.04-3.88) compared with placebo.CONCLUSIONS: Currently approved pharmacologic agents have varying effects on morbidity and functional status in patients with PAH. Future comparative effectiveness trials are warranted with a focus on a patient-centered approach to therapy. REGISTRATION: PROSPERO CRD42016036803CHEST 2017; 151(1):90-105 KEY WORDS: comparative efficacy; network meta-analysis; pulmonary arterial hypertension ABBREVIATIONS: 6MWD = 6-min walk distance; ERA = endothelin receptor antagonist; FDA = Food and Drug Administration; GRADE = Grading of Recommendations Assessment, Development, and Education; NYHA = New York Heart Association; PAH = pulmonary arterial hypertension; PDE5i = phosphodiesterase-5 inhibitor; RCT = randomized controlled trial; RR = risk ratio; SUCRA = surface under the cumulative ranking area; WHO = World Health Organization; WMD = weighted mean difference Pulmonary arterial hypertension (PAH) or World Health Organization (WHO) group 1 pulmonary hypertension is a progressive disease associated with significant morbidity and a 5% to 15% annual mortality rate. [1][2][3] In recent years, a number of drug classes to treat PAH have been approved for clinical use. These include endothelin receptor antagonists (ERA), phosphodiesterase-5 inhibitors (PDE5i), parenteral and nonparenteral prostacyclins, a soluble guanylate cyclase stimulator, and a prostacyclin-receptor agonist. Although randomized ...

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Section: Resultsmentioning

confidence: 99%

Comparative Effectiveness of Pharmacologic Interventions for Pulmonary Arterial Hypertension

Jain

Khera

Girotra

et al. 2017

Chest

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“…The frequentist approaches to NMA that can cope with large and complex networks, such as the routine in Stata that fits the multivariate random-effects meta-analysis model [33,39], have not been applied widely but are expected to be increasingly used in the next years. Similarly, the design-by-treatment interaction model to test for inconsistency [34] that was introduced in 2012 was used in only few networks.…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

“…Efthimiou inconsistency [33,34]. Their work enables researchers to fit models using frequentist software.…”

Section: Introduction Introduction Introductionmentioning

confidence: 99%

Bibliographic study showed improving statistical methodology of network meta-analyses published between 1999 and 2015

Πετροπούλου

Nikolakopoulou

Veroniki

et al. 2017

Journal of Clinical Epidemiology

109

138

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Objective: To assess the characteristics and core statistical methodology specific to network meta-analyses (NMAs) in clinical research articles. Study Design and What is new?Key findings Although the amount of evidence (the number of treatments and studies) included in published NMAs remains stable, the undertaking and reporting of statistical methods have significantly improved over the years. The assumptions underlying NMA are increasingly discussed and evaluated using appropriate methods. Less than 10% of NMAs published in 2014 and 2015 failed to evaluate the assumptions of the joint synthesis. What this adds to what is knownThis meta-epidemiological study presents the largest collection of published NMAs over the past 16 years. It provides an overview of the structural characteristics and statistical methodology of 456 published networks of interventions. It shows that the statistical methods in NMA have considerably improved in all aspects and some, such as the use of appropriate methods to evaluate the plausibility of the assumptions, are now routinely performed. We conclude that the increasingly populous community of NMA methodologists is quickly advancing through the learning curve of statistical methods employed in NMA. What is the implication, what should change nowThe updated description of the structural characteristics of the published NMAs can be used to inform pragmatic simulations studies and the development of methods that are relevant to the type of networks typically found in the medical literature. Future tutorials and training should be focused on improving the methodology and reporting on items that, although they have improved, their prevalence remains low, such as the formal exploration of heterogeneity and inconsistency and the presentation of all pairwise treatment effects.

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“…Results were presented as standardized mean difference (SMD) with 95 % confidence intervals (CIs) and odds ratio (OR) with 95 % CIs. In the network meta-analysis, a random-effects network metaanalysis was used for mixed multiple treatment comparisons, fully preserving the within-trial randomized treatment comparison of each trial [18]. The I 2 index was calculated to evaluate the extent of variability attributable to statistical heterogeneity between trials.…”

Section: Resultsmentioning

confidence: 99%

Intravesical treatment for interstitial cystitis/painful bladder syndrome: a network meta-analysis

et al. 2016

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Introduction and hypothesis Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic inflammatory condition of the submucosal and muscular layers of the bladder. So far, there is no effective and targeted treatment strategy for IC/ PBS. This study aimed to assess the efficacy and safety of intravesical instillation treatment in IC/PBS patients. Methods We searched various databases up to October 2015. A network meta-analysis was performed to compare global response assessment (GRA) for different treatment strategies, including botulinum toxin A (BoNTA), bacillus CalmetteGuerin (BCG), resiniferatoxin (RTX), lidocaine, chondroitin sulfate (CS), oxybutynin, and pentosan polysulfate (PPS). A traditional meta-analysis was also performed. Results Sixteen trials evaluating 905 patients were included. Network meta-analysis indicated that BoNTA had the highest probability of being the best treatment course according to GRA assessment results (probability 81.7 %). BCG or BoNTA therapy yielded significant improvement in GRA incidence according to traditional meta-analysis. Patients who received PPS showed higher urinary frequency results compared with the placebo groups. BCG-and PPS-treated patients had elevated urinary urgency treatment effects compared with placebo groups. Bladder capacity restoration results also showed significant improvements in patients who received BoNTA compared with placebo-treated individuals. Conclusions These findings indicate that BoNTA therapy has the highest probability of being the best therapy according to GRA, and significantly improves bladder capacity in IC/PBS patients. BCG treatment also significantly increases the incidence of GRA and improves the symptoms of urinary urgency. PPS can significantly improve urinary frequency and urgency symptoms in IC/PBS patients.

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Consistency and inconsistency in network meta‐analysis: model estimation using multivariate meta‐regression

Cited by 851 publications

References 29 publications

Comparative Effectiveness of Pharmacologic Interventions for Pulmonary Arterial Hypertension

Comparative Effectiveness of Pharmacologic Interventions for Pulmonary Arterial Hypertension

Bibliographic study showed improving statistical methodology of network meta-analyses published between 1999 and 2015

Intravesical treatment for interstitial cystitis/painful bladder syndrome: a network meta-analysis

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