Methods to induce labour: a systematic review, network meta-analysis and cost-effectiveness analysis.

OBJECTIVES: To compare the clinical effectiveness and cost-effectiveness of labour induction methods. METHODS: We conducted a systematic review of randomised trials comparing interventions for third-trimester labour induction (search date: March 2014). Network meta-analysis was possible for six of nine prespecified key outcomes: vaginal delivery within 24 hours (VD24), caesarean section, uterine hyperstimulation, neonatal intensive care unit (NICU) admissions, instrumental delivery and infant Apgar scores. We developed a decision-tree model from a UK NHS perspective and calculated incremental cost-effectiveness ratios, expected costs, utilities and net benefit, and cost-effectiveness acceptability curves. MAIN RESULTS: In all, 611 studies comparing 31 active interventions were included. Intravenous oxytocin with amniotomy and vaginal misoprostol (≥50 µg) were most likely to achieve VD24. Titrated low-dose oral misoprostol achieved the lowest odds of caesarean section, but there was considerable uncertainty in ranking estimates. Vaginal (≥50 µg) and buccal/sublingual misoprostol were most likely to increase uterine hyperstimulation with high uncertainty in ranking estimates. Compared with placebo, extra-amniotic prostaglandin E2 reduced NICU admissions. There were insufficient data to conduct analyses for maternal and neonatal mortality and serious morbidity or maternal satisfaction. Conclusions were robust after exclusion of studies at high risk of bias. Due to poor reporting of VD24, the cost-effectiveness analysis compared a subset of 20 interventions. There was considerable uncertainty in estimates, but buccal/sublingual and titrated (low-dose) misoprostol showed the highest probability of being most cost-effective. CONCLUSIONS: Future trials should be designed and powered to detect a method that is more cost-effective than low-dose titrated oral misoprostol. TWEETABLE ABSTRACT: New study ranks methods to induce labour in pregnant women on effectiveness and cost.

A checklist for critical appraisal of indirect comparisons.

The aim of this study was to develop a user-friendly checklist for critical appraisal of indirect comparisons of drugs, considering clinical, methodological/statistical and quality aspects, mainly to be applied in drug evaluation in the decision-making context. After conducting a review of the literature, we used group consensus to establish the key points of the checklist, focusing mainly on indirect comparisons, but including topics related to network meta-analysis or multiple treatment comparisons. The coordinating group elaborated the first draft, which was reviewed by external experts, re-evaluated by the coordinating group and finally assessed by 23 drug evaluation experts trained in indirect comparisons, who applied the checklist to one study. The Kappa index of agreement was calculated and the final checklist was developed by group consensus including the external experts. The checklist has two parts. The first consists of three eliminatory key questions while the second includes 17 items: 5 regarding quality, 5 regarding clinical issues and 7 dealing with methodology/statistics. The median kappa values of the 23 evaluations were 0.83 (range 0.67-0.93), 0.61 (0.54-0.91) and 0.36 (0.22-1) with regard to quality, clinical aspects and methodology/statistics, respectively. A structured checklist was developed to facilitate critical appraisal of key issues in indirect comparisons, including comments for assessing the consequences of its application to drug evaluation in the decision-making context. Agreement between reviewers in clinical and quality items was good, but weaker in methodology/statistics ones.

Waiting list may be a nocebo condition in psychotherapy trials: a contribution from network meta-analysis.

OBJECTIVE: Various control conditions have been employed in psychotherapy trials, but there is growing suspicion that they may lead to different effect size estimates. The present study aims to examine the differences among control conditions including waiting list (WL), no treatment (NT) and psychological placebo (PP). METHOD: We comprehensively searched for all randomized controlled trials (RCTs) comparing cognitive-behaviour therapies (CBT) against various control conditions in the acute phase treatment of depression, and applied network meta-analysis (NMA) to combine all direct and indirect comparisons among the treatment and control arms. RESULTS: We identified 49 RCTs (2730 participants) comparing WL, NT, PP and CBT. This network of evidence was consistent, and the effect size estimates for CBT were substantively different depending on the control condition. The odds ratio of response for NT over WL was statistically significant at 2.9 (95% CI: 1.3-5.7). However, the quality of evidence, including publication bias, was less than ideal and none of the preplanned sensitivity analyses limiting to high-quality studies could be conducted, while findings of significant differences did not persist in post hoc sensitivity analyses trying to adjust for publication bias. CONCLUSION: There may be important differences in control conditions currently used in psychotherapy trials.

Checking consistency in mixed treatment comparison meta-analysis.

Pooling of direct and indirect evidence from randomized trials, known as mixed treatment comparisons (MTC), is becoming increasingly common in the clinical literature. MTC allows coherent judgements on which of the several treatments is the most effective and produces estimates of the relative effects of each treatment compared with every other treatment in a network.We introduce two methods for checking consistency of direct and indirect evidence. The first method (back-calculation) infers the contribution of indirect evidence from the direct evidence and the output of an MTC analysis and is useful when the only available data consist of pooled summaries of the pairwise contrasts. The second more general, but computationally intensive, method is based on 'node-splitting' which separates evidence on a particular comparison (node) into 'direct' and 'indirect' and can be applied to networks where trial-level data are available. Methods are illustrated with examples from the literature. We take a hierarchical Bayesian approach to MTC implemented using WinBUGS and R.We show that both methods are useful in identifying potential inconsistencies in different types of network and that they illustrate how the direct and indirect evidence combine to produce the posterior MTC estimates of relative treatment effects. This allows users to understand how MTC synthesis is pooling the data, and what is 'driving' the final estimates.We end with some considerations on the modelling assumptions being made, the problems with the extension of the back-calculation method to trial-level data and discuss our methods in the context of the existing literature.

Mixed treatment comparison meta-analysis of complex interventions: psychological interventions in coronary heart disease.

Meta-analyses of psychological interventions typically find a pooled effect of "psychological intervention" compared with usual care. This answers the research question, "Are psychological interventions in general effective?" In fact, psychological interventions are usually complex with several different components. The authors propose that mixed treatment comparison meta-analysis methods may be a valuable tool when exploring the efficacy of interventions with different components and combinations of components, as this allows one to answer the research question, "Are interventions with a particular component (or combination of components) effective?" The authors illustrate the methods using a meta-analysis of psychological interventions for patients with coronary heart disease for a variety of outcomes. The authors carried out systematic literature searches to update an earlier Cochrane review and classified components of interventions into 6 types: usual care, educational, behavioral, cognitive, relaxation, and support. Most interventions were a combination of these components. There was some evidence that psychological interventions were effective in reducing total cholesterol and standardized mean anxiety scores, that interventions with behavioral components were effective in reducing the odds of all-cause mortality and nonfatal myocardial infarction, and that interventions with behavioral and/or cognitive components were associated with reduced standardized mean depression scores.

Meta-analysis of mixed treatment comparisons at multiple follow-up times.

Mixed treatment comparisons (MTC) meta-analysis is a methodology for making inferences on relative treatment effects based on a synthesis of both direct and indirect evidence on multiple treatment contrasts. This is particularly useful in the context of cost-effectiveness analysis and medical decision making. Here, we extend these methods to a more complex situation where trials report results at one or more, different yet fixed, follow-up times. These methods are applied to an illustrative data set combining evidence on healing rates under six different treatments for gastro-esophageal reflux disease (GERD). A series of Bayesian hierarchical models based on piece-wise exponential hazards is developed that borrow strength across the MTC networks and also across time points. These include models for absolute and relative treatment effects, models with fixed or random effects over time, random walk models, and models with homogeneous or heterogeneous between-trials variation. The deviance information criterion (DIC) is used to guide model development and selection. Models for absolute treatment effects generate materially different rankings of the treatments than models that separate the trial-specific baselines from the relative treatment effects. The extent of between-trials heterogeneity in treatment effects depends on treatment contrast. In discussion we note that models of this type have a very wide potential application.

Rapid diagnosis of thoracic aortic transection using intravenous digital subtraction angiography.

Rupture of the thoracic aorta associated with blunt trauma remains a frequently lethal injury. Although increasing numbers of patients with ruptured aortas are surviving to reach the hospital, the in-hospital mortality attending this injury remains high. Death due to transected aorta has been related to a delay in diagnosis. In an attempt to decrease the time necessary for diagnosis of this injury, we studied 50 patients using intravenous digital subtraction angiography (IVDSA) and conventional biplane angiography. We found that IVDSA was significantly faster than conventional biplane angiography, and that when IVDSA films are of diagnostic quality, they are sufficient to reliably demonstrate the presence of traumatic aortic transection. Our study was too small to establish whether IVDSA is a sufficiently sensitive test to exclude aortic injury. Further studies in this area need to be performed.

Selenium content of feeds and effect of dietary selenium on hair and blood serum.

A selenium depletion diet (.025 ppm selenium) was fed to two male Holstein calves for its effect on concentrations of selenium in serum. By 90 days, selenium in serum was depressed from .022 ppm to .013 ppm, and one of two calves had died of "possible white muscle disease." Repletion was rapid in that a diet containing .200 ppm selenium increased selenium in serum to .028 ppm within 2 wk. Dietary .280 ppm selenium increased it to .051 ppm in 1 wk. Eleven cows and eleven calves showed averages of .030 ppm in serum (range of .013 to .051 ppm) fed a diet of corn silage (.039 ppm) and supplement (.090 ppm). A sampling of feedstuffs showed a wide range of selenium among feedstuffs (.023 for corn cobs to 2.663 ppm for dried egg albumin) and a wide range within one type feedstuff (shelled corn, .017 to .219 ppm).