Cost effectiveness of nifedipine compared with atosiban in the treatment of threatened preterm birth (APOSTEL III trial).

OBJECTIVE: To assess the cost-effectiveness of treatment with nifedipine compared with atosiban in women with threatened preterm birth. DESIGN: An economic analysis alongside a randomised clinical trial (the APOSTEL III study). SETTING: Obstetric departments of 12 tertiary hospitals and seven secondary hospitals in the Netherlands and Belgium. POPULATION: Women with threatened preterm birth between 25 and 34 weeks of gestation, randomised for tocolysis with either nifedipine or atosiban. METHODS: We performed an economic analysis from a societal perspective. We estimated costs from randomisation until discharge. Analyses for singleton and multiple pregnancies were performed separately. The robustness of our findings was evaluated in sensitivity analyses. MAIN OUTCOME MEASURES: Mean costs and differences were calculated per woman treated with nifedipine or atosiban. Health outcomes were expressed as the prevalence of a composite of adverse perinatal outcomes. RESULTS: Mean costs per patients were significantly lower in the nifedipine group [singleton pregnancies: €34,897 versus €43,376, mean difference (MD) -€8479 [95% confidence interval (CI) -€14,327 to -€2016)]; multiple pregnancies: €90,248 versus €102,292, MD -€12,044 (95% CI -€21,607 to € -1671). There was a non-significantly higher death rate in the nifedipine group. The difference in costs was mainly driven by a lower neonatal intensive care unit admission (NICU) rate in the nifedipine group. CONCLUSION: Treatment with nifedipine in women with threatened preterm birth results in lower costs when compared with treatment with atosiban. However, the safety of nifedipine warrants further investigation. TWEETABLE ABSTRACT: In women with threatened preterm birth, tocolysis using nifedipine results in lower costs when compared with atosiban.

[Fibronectin test in threatened preterm labour: cost-saving but not yet widely implemented in the Netherlands]. / Fibronectinetest bij dreigende vroeggeboorte.

OBJECTIVE: Analysis of national implementation of the foetal fibronectin test in the diagnostics of threatened preterm labour in the Netherlands, and indication of the possible obstacles and consequences of implementation or no implementation. DESIGN: National questionnaire, retrospective cohort study and cost-effectiveness calculation. METHODS: We approached all hospitals in the Netherlands (n = 86) with a questionnaire on use of the fibronectin test. We also collected data on women who were referred to the Academic Medical Center (AMC), a tertiary care centre in Amsterdam, with symptoms of threatened preterm labour. We investigated whether the referred patients gave birth within 7 days, and whether unnecessary transfer to a centre with a neonatal intensive care unit (NICU) could have been avoided by implementation of the fibronectin test in the referring hospital. RESULTS: The fibronectin test was used in 34% of the hospitals and an additional 17% were in the process of implementation. The most important reasons not to use the fibronectin test were of a financial nature (50%). The cohort study included 96 women who were referred from secondary care. In our cohort, 36% of all transfers could have been avoided by implementation of the fibronectin test in secondary care. CONCLUSION: The fibronectin test can greatly reduce overtreatment and unnecessary transfer in threatened preterm labour, but implementation remains limited. Costs of the test are an obstacle for the referring hospitals, while implementation prevents unnecessary transport, admission and treatment of pregnant women, giving a potential saving of at least EUR 1,027,930 per year. Inclusion in the Netherlands Society for Obstetrics and Gynaecology (Nederlandse Vereniging voor Obstetrie en Gynaecologie, NVOG) guidelines would be a first step towards wider implementation. Slow implementation exemplifies a more widespread problem: the current reimbursement system does not stimulate such cost-saving innovations.

Comparing induction of labour with oral misoprostol or Foley catheter at term: cost-effectiveness analysis of a randomised controlled multi-centre non-inferiority trial.

OBJECTIVE: To assess the costs of labour induction with oral misoprostol versus Foley catheter. DESIGN: Economic evaluation alongside a randomised controlled trial. SETTING: Obstetric departments of six tertiary and 23 secondary care hospitals in the Netherlands. POPULATION: Women with a viable term singleton pregnancy in cephalic presentation, intact membranes, an unfavourable cervix (Bishop score <6) without a previous caesarean section, were randomised for labour induction with oral misoprostol (n = 924) or Foley catheter (n = 921). METHODS: We performed economic analysis from a hospital perspective. We estimated direct medical costs associated with healthcare utilisation from randomisation until discharge. The robustness of our findings was evaluated in sensitivity analyses. MAIN OUTCOME MEASURES: Mean costs and differences were calculated per women induced with oral misoprostol or Foley catheter. RESULTS: Mean costs per woman in the oral misoprostol group and Foley catheter group were €4470 versus €4158, respectively [mean difference €312, 95% confidence interval (CI) -€508 to €1063]. Multiple sensitivity analyses did not change these conclusions. However, if cervical ripening for low-risk pregnancies in the Foley catheter group was carried out in an outpatient setting, with admittance to labour ward only at start of active labour, the difference would be €4470 versus €3489, respectively (mean difference €981, 95% CI €225-1817). CONCLUSIONS: Oral misoprostol and Foley catheter generate comparable costs. Cervical ripening outside labour ward with a Foley catheter could potentially save almost €1000 per woman. TWEETABLE ABSTRACT: Oral misoprostol or Foley catheter for induction of labour generates comparable costs.

Cost-effectiveness of diagnostic testing strategies including cervical-length measurement and fibronectin testing in women with symptoms of preterm labor.

OBJECTIVE: To evaluate the cost-effectiveness of combining cervical-length (CL) measurement and fetal fibronectin (fFN) testing in women with symptoms of preterm labor between 24 and 34 weeks' gestation. METHODS: This was a model-based cost-effectiveness analysis evaluating seven test-treatment strategies based on CL measurement and/or fFN testing in women with symptoms of preterm labor from a societal perspective, in which neonatal outcomes and costs were weighted. Estimates of disease prevalence, test accuracy and costs were based on two recently performed nationwide cohort studies in The Netherlands. RESULTS: Strategies using fFN testing and CL measurement separately to predict preterm delivery are associated with higher costs and incidence of adverse neonatal outcomes compared with strategies that combine both tests. Additional fFN testing when CL is 15-30 mm was considered cost effective, leading to a cost saving of €3919 per woman when compared with a treat-all strategy, with a small deterioration in neonatal health outcomes, namely one additional perinatal death and 21 adverse outcomes per 10 000 women with signs of preterm labor (incremental cost-effectiveness ratios €39 million and €1.9 million, respectively). Implementing this strategy in The Netherlands, a country with about 180 000 deliveries annually, could lead to an annual cost saving of between €2.4 million and €7.6 million, with only a small deterioration in neonatal health outcomes. CONCLUSION: In women with symptoms of preterm labor at 24-34 weeks' gestation, performing additional fFN testing when CL is between 15 and 30 mm is a viable and cost-saving strategy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Cost-effectiveness of simulation-based team training in obstetric emergencies (TOSTI study).

OBJECTIVE: Team training is frequently applied in obstetrics. We aimed to evaluate the cost-effectiveness of obstetric multi-professional team training in a medical simulation centre. STUDY DESIGN: We performed a model-based cost-effectiveness analysis to evaluate four strategies for obstetric team training from a hospital perspective (no training, training without on-site repetition and training with 6 month or 3-6-9 month repetition). Data were retrieved from the TOSTI study, a randomised controlled trial evaluating team training in a medical simulation centre. We calculated the incremental cost-effectiveness ratio (ICER), which represent the costs to prevent the adverse outcome, here (1) the composite outcome of obstetric complications and (2) specifically neonatal trauma due to shoulder dystocia. RESULTS: Mean costs of a one-day multi-professional team training in a medical simulation centre were €25,546 to train all personnel of one hospital. A single training in a medical simulation centre was less effective and more costly compared to strategies that included repetition training. Compared to no training, the ICERs to prevent a composite outcome of obstetric complications were €3432 for a single repetition training course on-site six months after the initial training and €5115 for a three monthly repetition training course on-site after the initial training during one year. When we considered neonatal trauma due to shoulder dystocia, a three monthly repetition training course on-site after the initial training had an ICER of €22,878. CONCLUSION: Multi-professional team training in a medical simulation centre is cost-effective in a scenario where repetition training sessions are performed on-site.

An economic analysis of immediate delivery and expectant monitoring in women with hypertensive disorders of pregnancy, between 34 and 37 weeks of gestation (HYPITAT-II).

OBJECTIVE: To assess the economic consequences of immediate delivery compared with expectant monitoring in women with preterm non-severe hypertensive disorders of pregnancy. DESIGN: A cost-effectiveness analysis alongside a randomised controlled trial (HYPITAT-II). SETTING: Obstetric departments of seven academic hospitals and 44 non-academic hospitals in the Netherlands. POPULATION: Women diagnosed with non-severe hypertensive disorders of pregnancy between 340/7 and 370/7  weeks of gestation, randomly allocated to either immediate delivery or expectant monitoring. METHODS: A trial-based cost-effectiveness analysis was performed from a healthcare perspective until final maternal and neonatal discharge. MAIN OUTCOME MEASURES: Health outcomes were expressed as the prevalence of respiratory distress syndrome, defined as the need for supplemental oxygen for >24 hours combined with radiographic findings typical for respiratory distress syndrome. Costs were estimated from a healthcare perspective until maternal and neonatal discharge. RESULTS: The average costs of immediate delivery (n = 352) were €10 245 versus €9563 for expectant monitoring (n = 351), with an average difference of €682 (95% confidence interval, 95% CI -€618 to €2126). This 7% difference predominantly originated from the neonatal admissions, which were €5672 in the immediate delivery arm and €3929 in the expectant monitoring arm. CONCLUSION: In women with mild hypertensive disorders between 340/7 and 370/7  weeks of gestation, immediate delivery is more costly than expectant monitoring as a result of differences in neonatal admissions. These findings support expectant monitoring, as the clinical outcomes of the trial demonstrated that expectant monitoring reduced respiratory distress syndrome for a slightly increased risk of maternal complications. TWEETABLE ABSTRACT: Expectant management in preterm hypertensive disorders is less costly compared with immediate delivery.

Quantitative fetal fibronectin testing in combination with cervical length measurement in the prediction of spontaneous preterm delivery in symptomatic women.

OBJECTIVE: To evaluate whether in symptomatic women, the combination of quantitative fetal fibronectin (fFN) testing and cervical length (CL) improves the prediction of preterm delivery (PTD) within 7 days compared with qualitative fFN and CL. DESIGN: Post hoc analysis of frozen fFN samples of a nationwide cohort study. SETTING: Ten perinatal centres in the Netherlands. POPULATION: Symptomatic women between 24 and 34 weeks of gestation. METHODS: The risk of PTD <7 days was estimated in predefined CL and fFN strata. We used logistic regression to develop a model including quantitative fFN and CL, and one including qualitative fFN (threshold 50 ng/ml) and CL. We compared the models' capacity to identify women at low risk (<5%) for delivery within 7 days using a reclassification table. MAIN OUTCOME MEASURES: Spontaneous delivery within 7 days after study entry. RESULTS: We studied 350 women, of whom 69 (20%) delivered within 7 days. The risk of PTD in <7 days ranged from 2% in the lowest fFN group (<10 ng/ml) to 71% in the highest group (>500 ng/ml). Multivariable logistic regression showed an increasing risk of PTD in <7 days with rising fFN concentration [10-49 ng/ml: odds ratio (OR) 1.3, 95% confidence interval (95% CI) 0.23-7.0; 50-199 ng/ml: OR 3.2, 95% CI 0.79-13; 200-499 ng/ml: OR 9.0, 95% CI 2.3-35; >500 ng/ml: OR 39, 95% CI 9.4-164] and shortening of the CL (OR 0.86 per mm, 95% CI 0.82-0.90). Use of quantitative fFN instead of qualitative fFN resulted in reclassification of 18 (5%) women from high to low risk, of whom one (6%) woman delivered within 7 days. CONCLUSION: In symptomatic women, quantitative fFN testing does not improve the prediction of PTD within 7 days compared with qualitative fFN testing in combination with CL measurement in terms of reclassification from high to low (<5%) risk, but it adds value across the risk range. TWEETABLE ABSTRACT: Quantitative fFN testing adds value to qualitative fFN testing with CL measurement in the prediction of PTD.

Economic analysis of use of pessary to prevent preterm birth in women with multiple pregnancy (ProTWIN trial).

OBJECTIVE: To assess the cost-effectiveness of a cervical pessary to prevent preterm delivery in women with a multiple pregnancy. METHODS: The study design comprised an economic analysis of data from a randomized clinical trial evaluating cervical pessaries (ProTWIN). Women with a multiple pregnancy were included and an economic evaluation was performed from a societal perspective. Costs were estimated between the time of randomization and 6 weeks postpartum. The prespecified subgroup of women with a cervical length (CL) < 25(th) centile (< 38 mm) was analyzed separately. The primary endpoint was poor perinatal outcome occurring up to 6 weeks postpartum. Direct medical costs and health outcomes were estimated and incremental cost-effectiveness ratios for costs to prevent one poor outcome were calculated. RESULTS: Mean costs in the pessary group (n = 401) were € 21,783 vs € 21,877 in the group in which no pessary was used (n = 407) (difference, -€ 94; 95% CI, -€ 5975 to € 5609). In the prespecified subgroup of women with a CL < 38 mm we demonstrated a significant reduction in poor perinatal outcome (12% vs 29%; RR, 0.40; 95% CI, 0.19-0.83). Mean costs in the pessary group (n = 78) were € 25,141 vs € 30,577 in the no-pessary group (n = 55) (difference, -€ 5436 (95% CI, -€ 11,001 to € 1456). In women with a CL < 38 mm, pessary treatment was the dominant strategy (more effective and less costly) with a probability of 94%. CONCLUSION: Cervical pessaries in women with a multiple pregnancy involve costs comparable to those in women without pessary treatment. However, in women with a CL < 38 mm, treatment with a cervical pessary appears to be highly cost-effective.

Cost-effectiveness of induction of labour at term with a Foley catheter compared to vaginal prostaglandin E2 gel (PROBAAT trial).

OBJECTIVE: To assess the economic consequences of labour induction with Foley catheter compared to prostaglandin E2 gel. DESIGN: Economic evaluation alongside a randomised controlled trial. SETTING: Obstetric departments of one university and 11 teaching hospitals in the Netherlands. POPULATION: Women scheduled for labour induction with a singleton pregnancy in cephalic presentation at term, intact membranes and an unfavourable cervix; and without previous caesarean section. METHODS: Cost-effectiveness analysis from a hospital perspective. MAIN OUTCOME MEASURES: We estimated direct medical costs associated with healthcare utilisation from randomisation to 6 weeks postpartum. For caesarean section rate, and maternal and neonatal morbidity we calculated the incremental cost-effectiveness ratios, which represent the costs to prevent one of these adverse outcomes. RESULTS: Mean costs per woman in the Foley catheter group (n = 411) and in the prostaglandin E2 gel group (n = 408), were €3297 versus €3075, respectively, with an average difference of €222 (95% confidence interval -€157 to €633). In the Foley catheter group we observed higher costs due to longer labour ward occupation and less cost related to induction material and neonatal admissions. Foley catheter induction showed a comparable caesarean section rate compared with prostaglandin induction, therefore the incremental cost-effectiveness ratio was not informative. Foley induction resulted in fewer neonatal admissions (incremental cost-effectiveness ratio €2708) and asphyxia/postpartum haemorrhage (incremental cost-effectiveness ratios €5257) compared with prostaglandin induction. CONCLUSIONS: Foley catheter and prostaglandin E2 labour induction generate comparable costs.