BackgroundMore than 150,000 pregnant women in England and Wales have their labour induced each year. Multiple pharmacological, mechanical and complementary methods are available to induce labour.ObjectiveTo assess the relative effectiveness, safety and cost-effectiveness of labour induction methods and, data permitting, effects in different clinical subgroups.MethodsWe carried out a systematic review using Cochrane methods. The Cochrane Pregnancy and Childbirth Group’s Trials Register was searched (March 2014). This contains over 22,000 reports of controlled trials (published from 1923 onwards) retrieved from weekly searches of OVID MEDLINE (1966 to current); Cochrane Central Register of Controlled Trials (The Cochrane Library); EMBASE (1982 to current); Cumulative Index to Nursing and Allied Health Literature (1984 to current); ClinicalTrials.gov; the World Health Organization International Clinical Trials Registry Portal; and hand-searching of relevant conference proceedings and journals. We included randomised controlled trials examining interventions to induce labour compared with placebo, no treatment or other interventions in women eligible for third-trimester induction. We included outcomes relating to efficacy, safety and acceptability to women. In addition, for the economic analysis we searched the Database of Abstracts of Reviews of Effects, and Economic Evaluations Databases, NHS Economic Evaluation Database and the Health Technology Assessment database. We carried out a network meta-analysis (NMA) using all of the available evidence, both direct and indirect, to produce estimates of the relative effects of each treatment compared with others in a network. We developed a de novo decision tree model to estimate the cost-effectiveness of various methods. The costs included were the intervention and other hospital costs incurred (price year 2012–13). We reviewed the literature to identify preference-based utilities for the health-related outcomes in the model. We calculated incremental cost-effectiveness ratios, expected costs, utilities and net benefit. We represent uncertainty in the optimal intervention using cost-effectiveness acceptability curves.ResultsWe identified 1190 studies; 611 were eligible for inclusion. The interventions most likely to achieve vaginal delivery (VD) within 24 hours were intravenous oxytocin with amniotomy [posterior rank 2; 95% credible intervals (CrIs) 1 to 9] and higher-dose (≥ 50 µg) vaginal misoprostol (rank 3; 95% CrI 1 to 6). Compared with placebo, several treatments reduced the odds of caesarean section, but we observed considerable uncertainty in treatment rankings. For uterine hyperstimulation, double-balloon catheter had the highest probability of being among the best three treatments, whereas vaginal misoprostol (≥ 50 µg) was most likely to increase the odds of excessive uterine activity. For other safety outcomes there were insufficient data or there was too much uncertainty to identify which treatments performed ‘best’. Few studies collected information on women’s views. Owing to incomplete reporting of the VD within 24 hours outcome, the cost-effectiveness analysis could compare only 20 interventions. The analysis suggested that most interventions have similar utility and differ mainly in cost. With a caveat of considerable uncertainty, titrated (low-dose) misoprostol solution and buccal/sublingual misoprostol had the highest likelihood of being cost-effective.LimitationsThere was considerable uncertainty in findings and there were insufficient data for some planned subgroup analyses.ConclusionsOverall, misoprostol and oxytocin with amniotomy (for women with favourable cervix) is more successful than other agents in achieving VD within 24 hours. The ranking according to safety of different methods was less clear. The cost-effectiveness analysis suggested that titrated (low-dose) oral misoprostol solution resulted in the highest utility, whereas buccal/sublingual misoprostol had the lowest cost. There was a high degree of uncertainty as to the most cost-effective intervention.Future workFuture trials should be powered to detect a method that is more cost-effective than misoprostol solution and report outcomes included in this NMA.Study registrationThis study is registered as PROSPERO CRD42013005116.FundingThe National Institute for Health Research Health Technology Assessment programme.

ObjeCtives To assess the effectiveness and safety of prostaglandins used for labour induction. Design Systematic review with Bayesian network metaanalysis Data sOurCesThe Cochrane Pregnancy and Childbirth Group's Database of Trials (which incorporates the results of a broad generic search for all pregnancy and postpartum trials). Sources included are CENTRAL, Medline, Embase, NHS Economic Evaluation Database, CINAHL, relevant journals, conference proceedings, and registries of ongoing trials.eligibility Criteria fOr seleCting stuDies Randomised clinical trials of prostaglandin or prostaglandin analogues used for third trimester cervical ripening or labour induction versus placebo or no treatment, alternative prostaglandin dose or administration, or a different type of prostaglandin. We included studies recruiting women with a viable fetus, but had no other restrictions relating to indication for labour induction or language of publication. Outcomes assessed were serious neonatal morbidity (trialist defined) or perinatal death; serious maternal morbidity (trialist defined) or death; vaginal delivery not achieved within 24 hours, caesarean section, and uterine hyperstimulation with fetal heart rate changes. results 280 randomised clinical trials were included (48 068 women) in the review. Maternal and neonatal mortality and serious morbidity were rarely reported and are summarized narratively. Unresolved inconsistency was observed for the hyperstimulation outcome. Relative to placebo, the odds of failing to achieve a vaginal delivery were lowest for vaginal misoprostol (≥ 50 μg) (odds ratio 0.06 (95% credible interval 0.02 to 0.12)), with a 39% absolute probability of event (95% credible interval 1% to 94%). Compared with placebo, odds of caesarean section were lowest for titrated oral misoprostol solution ( < 50 μg) (odds ratio 0.65 (0.49 to 0.83)), with an absolute probability of event of 15% (3% to 40%). COnClusiOnsLow dose( < 50 μg) titrated oral misoprostol solution had the lowest probability of caesarean section, whereas vaginal misprostol (≥50 μg) had the highest probability of achieving a vaginal delivery within 24 hours. These findings have important implications for a series of current national and international guidelines for induction of labour and future research in this area. systematiC review registratiOn PROSPERO 2013:CRD42013005116 IntroductionLabour inductions have increased steadily over the past two decades, with overall rates in many countries now exceeding 20% of all births. 1 2 Many different methods have been used, but prostaglandins remain a preferred method for cervical ripening and labour induction. 1 3 4 Although various prostaglandins have been tested in randomised trials, current recommendations have not been based on a quantitative overview of the accumulated evidence of their effectiveness and safety. Published meta-analyses have focused on pairwise "head to head" comparisons, 5-7 but clinicians, women, and policy makers tend to make informal indirect comparisons between dif...

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As more complex meta-analytical techniques such as network and multivariate meta-analyses become increasingly common, further pressures are placed on reviewers to extract data in a systematic and consistent manner. Failing to do this appropriately wastes time, resources and jeopardises accuracy. This guide (data extraction for complex meta-analysis (DECiMAL)) suggests a number of points to consider when collecting data, primarily aimed at systematic reviewers preparing data for meta-analysis. Network meta-analysis (NMA), multiple outcomes analysis and analysis combining different types of data are considered in a manner that can be useful across a range of data collection programmes. The guide has been shown to be both easy to learn and useful in a small pilot study.Electronic supplementary materialThe online version of this article (doi:10.1186/s13643-016-0368-4) contains supplementary material, which is available to authorized users.

ObjectivesTo compare the clinical effectiveness and cost‐effectiveness of labour induction methods.MethodsWe 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 resultsIn 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.ConclusionsFuture trials should be designed and powered to detect a method that is more cost‐effective than low‐dose titrated oral misoprostol.Tweetable abstractNew study ranks methods to induce labour in pregnant women on effectiveness and cost.