Cost Implications of Using Carbetocin Injection to Prevent Postpartum Hemorrhage in a Canadian Urban Hospital.

OBJECTIVE: Recent World Health Organization (WHO) recommendations regarding uterotonics for the prevention of postpartum hemorrhage (PPH) state that carbetocin should be considered a first-line prophylactic agent for all births where its cost is comparable to other effective uterotonics. This study evaluated whether a room temperature stable formulation of carbetocin met this recommendation in a Canadian urban hospital setting. METHODS: A decision tree model was developed to assess the financial implications of replacing oxytocin with carbetocin as a first-line prophylactic agent for PPH prevention in a Greater Toronto Area (GTA) hospital. The analysis accounted for the mode of delivery, efficacies of carbetocin and oxytocin in PPH prevention, occurrence of PPH-related health outcomes, and health care resource costs for PPH interventions. RESULTS: This study found that a GTA hospital, with 3242 deliveries per year, could save over CAD $349 000 annually by switching to room temperature stable carbetocin for PPH prevention. Carbetocin was able to lower institution costs by reducing the use of health care resources for PPH management in low-risk and high-risk PPH patients. The cost-saving potential of carbetocin relative to oxytocin was largely attributed to its greater efficacy in preventing the consequences of PPH. CONCLUSION: The use of room temperature stable carbetocin as a first-line prophylactic agent for PPH prevention meets WHO recommendations regarding uterotonics for PPH in a GTA hospital. The model from this study can be used to determine the financial impact of switching from oxytocin to carbetocin in other jurisdictions while diversifying a hospital's pool of PPH prophylactic agents.

Cost-effectiveness of inhaled oxytocin for prevention of postpartum haemorrhage: a modelling study applied to two high burden settings.

BACKGROUND: Access to oxytocin for prevention of postpartum haemorrhage (PPH) in resource-poor settings is limited by the requirement for a consistent cold chain and for a skilled attendant to administer the injection. To overcome these barriers, heat-stable, non-injectable formulations of oxytocin are under development, including oxytocin for inhalation. This study modelled the cost-effectiveness of an inhaled oxytocin product (IHO) in Bangladesh and Ethiopia. METHODS: A decision analytic model was developed to assess the cost-effectiveness of IHO for the prevention of PPH compared to the standard of care in Bangladesh and Ethiopia. In Bangladesh, introduction of IHO was modelled in all public facilities and home deliveries with or without a skilled attendant. In Ethiopia, IHO was modelled in all public facilities and home deliveries with health extension workers. Costs (costs of introduction, PPH prevention and PPH treatment) and effects (PPH cases averted, deaths averted) were modelled over a 12-month program. Life years gained were modelled over a lifetime horizon (discounted at 3%). Cost of maintaining the cold chain or effects of compromised oxytocin quality (in the absence of a cold chain) were not modelled. RESULTS: In Bangladesh, IHO was estimated to avert 18,644 cases of PPH, 76 maternal deaths and 1954 maternal life years lost. This also yielded a cost-saving, with the majority of gains occurring among home deliveries where IHO would replace misoprostol. In Ethiopia, IHO averted 3111 PPH cases, 30 maternal deaths and 767 maternal life years lost. The full IHO introduction program bears an incremental cost-effectiveness ratio (ICER) of between 2 and 3 times the per-capita Gross Domestic Product (GDP) ($1880 USD per maternal life year lost) and thus is unlikely to be considered cost-effective in Ethiopia. However, the ICER of routine IHO administration considering recurring cost alone falls under 25% of per-capita GDP ($175 USD per maternal life-year saved). CONCLUSIONS: IHO has the potential to expand access to uterotonics and reduce PPH-associated morbidity and mortality in high burden settings. This can facilitate reduced spending on PPH management, making the product highly cost-effective in settings where coverage of institutional delivery is lagging.

Carbetocin: Worth the extra expense?

Every six minutes, a mother dies from post-partum haemorrhage (PPH) in low- and middle-income countries, often in the prime of her life and often leaving behind a young family. To prevent PPH, the routine administration of a uterus-contracting ('uterotonic') agent is a standard practice across the world. Oxytocin is the standard uterotonic agent recommended for this purpose, and is recommended for all women giving birth. Oxytocin is problematic as it requires cold storage and transport, and in low-resource settings, the cold chain is not commonly available. Hence, using heat-stable carbetocin in these settings can be advantageous. Heat-stable carbetocin is a promising alternative to oxytocin. Because of its heat stability, it can overcome the persistent problems with oxytocin quality as it does not require cold chain for storage and transport. Considering the totality of the evidence, it appears to have some additional desirable effects compared with oxytocin and a very favourable side effect profile similar to oxytocin. However, because carbetocin costs 20 times more than oxytocin and is not widely available yet, oxytocin remains the mainstay for prevention of PPH. However, this may change as WHO has signed a memorandum of understanding with the manufacturer to provide carbetocin for the public sector of LMIC at a similar price level to that of oxytocin. Currently, carbetocin is being registered in 90 low- and middle-income countries to be made available and improve access to this life-saving uterotonic agent.

A systematic review of the cost-effectiveness of uterotonic agents for the prevention of postpartum hemorrhage.

BACKGROUND: Several uterotonic options exist for prevention of postpartum hemorrhage (PPH); hence, cost-effectiveness is an important decision-making criterion affecting uterotonic choice. OBJECTIVE: To conduct a systematic review of cost-effectiveness of uterotonics for PPH prevention to support a WHO guideline update. SEARCH STRATEGY: We searched major databases from 1980 to June 2018 and the National Health Services Economic Evaluation (NHS EED) database from inception (1995) to March 2015 for eligible studies. SELECTION CRITERIA: We included comparative economic evaluations, cost-utility analyses, and resource-utilization studies. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed studies and extracted data organized by birth mode and setting. MAIN RESULTS: We included 15 studies across all income categories that compared misoprostol versus no uterotonic (five studies) or versus oxytocin (one study), carbetocin versus oxytocin (eight studies), and one study comparing numerous uterotonics. In specific low-resource contexts, we found reasonably good evidence that misoprostol was cost-effective compared with no uterotonic. In the context of cesarean delivery, carbetocin was more cost favorable than oxytocin but certainty of this evidence was low. CONCLUSIONS: Evidence on the cost-effectiveness of various uterotonic agents was not generalizable. As the number of competing uterotonics increases, rigorous economic evaluations including contextual factors are needed.

Clinical and financial evaluation of carbetocin as postpartum haemorrhage prophylaxis at caesarean section: A retrospective cohort study.

BACKGROUND: The long-acting oxytocic agent; carbetocin, has been consistently shown to reduce the need for additional uterotonics at caesarean section, but not postpartum haemorrhage (PPH). While promising, current evidence is limited by heterogenicity in study design and findings. AIMS: To examine whether carbetocin confers clinical or economic benefit compared to oxytocin at caesarean section in an all-risk Australian population. MATERIALS AND METHODS: A retrospective cohort study was undertaken of all singleton caesarean sections at a public tertiary hospital from 2008 to 2010 (n = 2499). From 1 January 2008 to 24 March 2009 all women received prophylactic oxytocin 5-10 units slow push intravenously at delivery, after which all patients received 100 µg intravenous carbetocin. Outcomes were PPH (≥1000 mL) and the requirement of secondary uterotonics. A post hoc cost analysis was also performed. RESULTS: A total of 1467 and 1024 patients received carbetocin and oxytocin, respectively. Incidence of PPH ≥1000 mL was 7.8% for carbetocin compared to and 9.7% for oxytocin (odds ratio (OR) 0.79, 95% CI 0.59-1.05). Moderate blood loss >500 mL was significantly reduced with carbetocin; occurring in 27.3% versus 39.4% (OR 0.57, 95% CI 0.49-0.68). There was a 20.0% reduction in secondary uterotonic treatment with carbetocin (OR 0.42, 95% CI 0.35-0.49). Average drug costs were lower with oxytocin at $4.74 versus $36.42/patient. However, the 1.9% reduction in PPH with carbetocin resulted in a $63.46 reduction in cost per patient, with a cost-effectiveness ratio of $1667 to prevent one case of PPH ≥1000 mL. CONCLUSIONS: Carbetocin reduced moderate blood loss >500 mL, but not PPH ≥1000 mL. Carbetocin conferred a 20% reduction in secondary uterotonic treatment, as well as lowering direct medical costs.

Cost-effectiveness of Carbetocin versus Oxytocin for Prevention of Postpartum Hemorrhage Resulting from Uterine Atony in Women at high-risk for bleeding in Colombia.

OBJECTIVE: To assess the cost-effectiveness of carbetocin versus oxytocin for prevention of postpartum hemorrhage (PPH) due to uterine atony after vaginal delivery/cesarean section in women with risk factors for bleeding. METHODS: A decision tree was developed for vaginal delivery and another one for cesarean, in which a sequential analysis of the results was obtained with the use of carbetocin and oxytocin for prevention of PPH and related consequences. A third-party payer perspective was used; only direct medical costs were considered. Incremental costs and effectiveness in terms of quality-adjusted life years (QALYs) were evaluated for a one-year time horizon. The costs were expressed in 2016 Colombian pesos (1 USD = 3,051 Col$). RESULTS: In the vaginal delivery model, the average cost of care for a patient receiving prophylaxis with uterotonic agents was Col$ 347,750 with carbetocin and Col$ 262,491 with oxytocin, while the QALYs were 0.9980 and 0.9979, respectively. The incremental cost-effectiveness ratio is above the cost-effectiveness threshold adopted by Colombia. In the model developed for cesarean section, the average cost of a patient receiving prophylaxis with uterotonics was Col$ 461,750 with carbetocin, and Col$ 481,866 with oxytocin, and the QALYs were 0.9959 and 0.9926, respectively. Carbetocin has lower cost and is more effective, with a saving of Col$ 94,887 per avoided hemorrhagic event. CONCLUSION: In case of elective cesarean delivery, carbetocin is a dominant alternative in the prevention of PPH compared with oxytocin; however, it presents higher costs than oxytocin, with similar effectiveness, in cases of vaginal delivery.

OBJETIVO: Avaliar a relação custo-eficácia da carbetocina versus oxitocina para prevenção de hemorragia pós-parto (HPP) vaginal e cesariana devido à atonia uterina em mulheres com fatores de risco para desenvolver sangramento. MéTODOS: Foram desenvolvidos protocolos de manejo para parto vaginal e outra para parto por cesárea e analisados resultados obtidos com carbetocina e oxitocina na prevenção de HPP, assim como, consequências relacionadas à ocorrência do evento hemorrágico. A perspectiva utilizada foi a do terceiro pagador, portanto, apenas os custos médicos diretos foram levados em consideração. Os custos incrementais e a eficácia em termos de anos de vida ajustados pela qualidade (QALY) foram avaliados para um horizonte de tempo de um ano. Os custos foram expressos em pesos colombianos de 2016 (1 USD = 3.051 Col$). RESULTADOS: No modelo de parto vaginal, o custo médio de cuidados para um paciente que recebeu profilaxia com agentes uterotônicos foi de Col$ 347.750 com carbetocina e Col$ 262.491 com oxitocina, enquanto os QALYs foram 0,9980 e 0,9979, respectivamente. O índice incremental de custo-efetividade está acima do limite de custo-efetividade adotado pela Colômbia. No modelo desenvolvido para parto por cesárea, o custo médio do paciente que recebeu profilaxia com terapia uterotônica foi de Col$ 461.750 com carbetocina e Col$ 481.866 com oxitocina e os QALYs foram 0,9959 e 0,9926, respectivamente. A carbetocina foi a alternativa com menor custo e maior efetividade com uma economia de $94.887 por evento hemorrágico evitado. CONCLUSãO: A carbetocina no parto eletivo por cesárea é uma alternativa dominante na prevenção da PPH em relação à oxitocina; porém representa custos mais altos com uma eficácia similar à da oxitocina no caso de parto vaginal.

Cost-effectiveness of carbetocin versus oxytocin for prevention of postpartum hemorrhage resulting from uterine atony in women at high-risk for bleeding in Colombia / Rendimento da carbetocina versus oxitocina para a prevenção da hemorragia pós-parto resultante da atonia uterina em mulheres com alto risco de sangramento na Colômbia

Abstract Objective To assess the cost-effectiveness of carbetocin versus oxytocin for prevention of postpartum hemorrhage (PPH) due to uterine atony after vaginal delivery/ cesarean section in women with risk factors for bleeding. Methods A decision treewas developed for vaginal delivery andanother one for cesarean, in which a sequential analysis of the results was obtained with the use of carbetocin and oxytocin for prevention of PPH and related consequences. A third-party payer perspective was used; only directmedical costs were considered. Incremental costs and effectiveness in terms of quality-adjusted life years (QALYs) were evaluated for a one-year timehorizon. The costs were expressed in 2016 Colombian pesos (1 USD = 3,051 Col$). Results In the vaginal delivery model, the average cost of care for a patient receiving prophylaxis with uterotonic agents was Col$ 347,750 with carbetocin and Col$ 262,491 with oxytocin,while theQALYs were 0.9980 and 0.9979, respectively. The incremental costeffectiveness ratio is above the cost-effectiveness threshold adopted by Colombia. In the model developed for cesarean section, the average cost of a patient receiving prophylaxis with uterotonics was Col$ 461,750 with carbetocin, and Col$ 481,866 with oxytocin, and the QALYs were 0.9959 and 0.9926, respectively. Carbetocin has lower cost and is more effective, with a saving of Col$ 94,887 per avoided hemorrhagic event. Conclusion In case of elective cesarean delivery, carbetocin is a dominant alternative in the prevention of PPH compared with oxytocin; however, it presents higher costs than oxytocin, with similar effectiveness, in cases of vaginal delivery.

Resumo Objetivo Avaliar a relação custo-eficácia da carbetocina versus oxitocina para prevenção de hemorragia pós-parto (HPP) vaginal e cesariana devido à atonia uterina em mulheres com fatores de risco para desenvolver sangramento. Métodos Foram desenvolvidos protocolos de manejo para parto vaginal e outra para parto por cesárea e analisados resultados obtidos com carbetocina e oxitocina na prevenção de HPP, assim como, consequências relacionadas à ocorrência do evento hemorrágico. A perspectiva utilizada foi a do terceiro pagador, portanto, apenas os custos médicos diretos foram levados em consideração. Os custos incrementais e a eficácia em termos de anos de vida ajustados pela qualidade (QALY) foram avaliados para um horizonte de tempo de um ano. Os custos foram expressos em pesos colombianos de 2016 (1 USD = 3.051 Col$). Resultados No modelo de parto vaginal, o customédio de cuidados para um paciente que recebeu profilaxia com agentes uterotônicos foi de Col$ 347.750 com carbetocina e Col$ 262.491 com oxitocina, enquanto os QALYs foram 0,9980 e 0,9979, respectivamente. O índice incremental de custo-efetividade está acima do limite de custoefetividade adotado pela Colômbia. No modelo desenvolvido para parto por cesárea, o custo médio do paciente que recebeu profilaxia com terapia uterotônica foi de Col$ 461.750 com carbetocina e Col$ 481.866 com oxitocina e os QALYs foram 0,9959 e 0,9926, respectivamente. A carbetocina foi a alternativa com menor custo e maior efetividade com uma economia de $94.887 por evento hemorrágico evitado. Conclusão A carbetocina no parto eletivo por cesárea é uma alternativa dominante na prevenção da PPH em relação à oxitocina; porém representa custos mais altos com uma eficácia similar à da oxitocina no caso de parto vaginal.

Cost effectiveness analysis of carbetocin during cesarean section in a high volume maternity unit.

AIM: To evaluate the cost effectiveness of carbetocin compared to oxytocin when used as prophylaxis against post-partum hemorrhage (PPH) during cesarean deliveries. METHODS: A systematic review of the literature was performed to identify randomized controlled trials that compared the use of carbetocin to oxytocin in the context of cesarean deliveries. Cost effectiveness analysis was then performed using secondary data from the perspective of a maternity unit within the Malaysian Ministry of Health, over a 24 h time period. RESULTS: Seven randomized controlled trials with over 2000 patients comparing carbetocin with oxytocin during cesarean section were identified. The use of carbetocin in our center, which has an average of 3000 cesarean deliveries annually, would have prevented 108 episodes of PPH, 104 episodes of transfusion and reduced the need for additional uterotonics in 455 patients. The incremental cost effectiveness ratio of carbetocin for averting an episode of PPH was US$278.70. CONCLUSION: Reduction in retreatment, staffing requirements, transfusion and potential medication errors mitigates the higher index cost of carbetocin. From a pharmacoeconomic perspective, in the context of cesarean section, carbetocin was cost effective as prophylaxis against PPH. Ultimately, the relative value placed on the outcomes above and the individual unit's resources would influence the choice of uterotonic.

Pharmacoeconomic study comparing carbetocin with oxytocin for the prevention of hemorrhage following cesarean delivery in Lima, Peru.

Postpartum hemorrhage is one of the main causes of maternal death. Oxytocin has traditionally been used to prevent postpartum hemorrhage. AIM: To compare oxytocin with carbetocin, a long-acting analog of oxytocin, for prevention of uterine hemorrhage after cesarean delivery. MATERIALS & METHODS: Clinical data were retrieved from the 2012 Cochrane meta-analysis "Carbetocin for preventing postpartum hemorrhage". A decision tree was constructed. The direct costs were those of medications from the Peruvian official price list (DIGEMID). Costs associated with additional oxytocic drugs, blood transfusions, postpartum hemorrhage kits and hysterectomy were obtained from Hospital Nacional Edgardo Rebagliati Martins. The perspective of the study was that of the payer. The time horizon for calculating quality-adjusted life years (QALYs) was 1 year (2015). RESULTS: Patients who received carbetocin required fewer additional uterotonic agents, had fewer hemorrhages and received fewer blood transfusions. Therefore, the costs associated with these interventions were lower. The incremental cost-effectiveness ratio was S/. 49,918 per QALY gained, which is lower than the threshold we estimated for Peru. CONCLUSION: Carbetocin is more cost-effective than oxytocin for prevention of uterine hemorrhage after cesarean delivery.

Analysis of the cost-effectiveness of carbetocin for the prevention of hemorrhage following cesarean delivery in Ecuador.

AIM: To compare the cost of carbetocin with that of oxytocin for the prevention and management of hemorrhage following cesarean delivery in Ecuador. MATERIALS & METHODS: We developed a decision tree based cost-effectiveness model to compare carbetocin with oxytocin in the prevention of hemorrhage following cesarean delivery in Ecuador. Our model was run from a third party payer perspective and was validated by local experts in the field. The efficacy of the interventions was determined based on a systematic review of the literature. Direct costs were calculated based on current National Health Service price lists and retail price. Since the period covered by the analysis was 1 year, costs and health effects were not discounted. RESULTS: The difference in costs between the interventions was US$16.26, with a difference in effectiveness of 0.0067 disability adjusted life years averted. The incremental cost-effectiveness ratio for carbetocin compared with oxytocin for prevention of hemorrhage following cesarean delivery was US$2432.89 per disability adjusted life year averted. CONCLUSION: Carbetocin is as efficacious and safe as oxytocin for primary prevention of hemorrhage in cesarean delivery in Ecuador. It is highly cost effective for reducing the need for additional uterotonic drugs in both emergency and elective cesarean delivery.

A prospective cohort study evaluating the cost-effectiveness of carbetocin for prevention of postpartum haemorrhage in caesarean sections.

Postpartum haemorrhage (PPH) is the leading cause of maternal mortality worldwide. Prophylaxis with oxytocic medication is recommended by the WHO to prevent its occurrence. Carbetocin is a newer oxytocic, with potential to lower PPH rates, reduce the total use of oxytocic drugs and lead to financial savings. Meta-analyses have confirmed a reduction in the use of additional oxytocic medication with the use of carbetocin compared to oxytocin. However, there are few studies evaluating the costs of carbetocin prophylaxis. We carried out a prospective cohort study evaluating the financial impact of carbetocin, following its introduction at our centre for caesarean section. We collected data for 400 patients in total, making this, to our knowledge, the largest study conducted on this topic. We found a significant reduction in PPH rates and the use of additional oxytocics with projected overall financial savings of £68.93 per patient with the use of carbetocin. Impact statement It is well established that carbetocin reduces the use of secondary oxytocics compared to oxytocin alone in the active management of the third stage of labour. Evidence for reduction of post-partum haemorrhage and its cost effectiveness are more equivocal. Our study demonstrates that carbetocin also reduces post-partum haemorrhage, use of blood and blood products and midwifery recovery time in the setting of caesarean section. We have also demonstrated that despite the increased index cost of carbetocin it delivers an overall substantial cost benefit. The implications of these findings are of reduced morbidity, faster recovery and cost savings in these times of austerity in the UK. It allows more efficient labour distribution of midwives, particularly in the setting of staff shortages across the NHS. A randomised control trial in this area needs to be conducted to determine the cost benefit of carbetocin and with this and post-partum haemorrhage rates as the primary outcome measures.

Carbetocin versus oxytocin for prevention of post-partum haemorrhage at caesarean section in the United Kingdom: An economic impact analysis.

OBJECTIVE: To determine the economic impact of the introduction of carbetocin for the prevention of postpartum haemorrhage (PPH) at caesarean section, compared to oxytocin. STUDY DESIGN: The model is a decision tree conducted from a UK National Health Service perspective. 1500 caesarean sections (both elective and emergency) were modelled over a 12 month period. Efficacy data was taken from a published Cochrane meta-analysis, and costs from NHS Reference costs, the British National Formulary and the NHS electronic Medicines Information Tool. A combination of hospital audit data and expert input from an advisory board of clinicians was used to inform resource use estimates. The main outcome measures were the incidence of PPH and total cost over a one year time horizon, as a result of using carbetocin compared to oxytocin for prevention of PPH at caesarean section. RESULTS: The use of carbetocin compared to oxytocin for prevention of PPH at caesarean section was associated with a reduction of 30 (88 vs 58) PPH events (>500ml blood loss), and a cost saving of £27,518. In probabilistic sensitivity analysis, carbetocin had a 91.5% probability of producing better outcomes, and a 69.4% chance of being dominant (both cheaper and more effective) compared to oxytocin. CONCLUSION: At list price, the introduction of carbetocin appears to provide improved clinical outcomes along with cost savings, though this is subject to uncertainty regarding the underlying data in efficacy, resource use, and cost.

Costs of the use of carbetocin in the prevention of uterine atony following delivery of the infant by Caesarean section - retrospective multicenter study.

OBJECTIVES: The aim of this study was to compare the costs of using carbetocin in the prevention of uterine atony following delivery of the infant by Cesarean section (C-section) under epidural or spinal anesthesia with standard methods of prevention (SMP). MATERIAL AND METHODS: This retrospective multicenter study was based on data from three medical centers. A questionnaire was developed to gather patient records on consumption and costs of resources related to C-section, prevention of uterine atony and postpartum hemorrhage (PPH) treatment. Six subpopulations were considered, depending on patient characteristics. The analysis covered two perspectives: that of the hospital and of the public payer. RESULTS: The subpopulations were homogenous, which was a premise for pooling the data. The use of carbetocin in the prevention of uterine atony following Cesarean section generates savings for hospital in comparison with SMP (oxytocin) in 5 of 6 subpopulations. The biggest savings were observed amongst patients who experienced severe PPH and reached 2.6-6.2 thousand PLN per patient. Costs of services related to C-section borne by the hospitals were higher than the refund received from a public payer. The greatest underestimation reached 12.1 thousand PLN per patient. Nevertheless, loss generated by this underfunding was lower in carbetocin versus oxytocin group. CONCLUSIONS: The use of carbetocin instead of SMP gives hospitals an opportunity to make savings as well as to reduce losses resulting from the underfunding of the services provided by the National Health Fund.

Which method is best for the induction of labour? A systematic review, network meta-analysis and cost-effectiveness analysis.

BACKGROUND: More 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. OBJECTIVE: To assess the relative effectiveness, safety and cost-effectiveness of labour induction methods and, data permitting, effects in different clinical subgroups. METHODS: We 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. RESULTS: We 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. LIMITATIONS: There was considerable uncertainty in findings and there were insufficient data for some planned subgroup analyses. CONCLUSIONS: Overall, 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 WORK: Future trials should be powered to detect a method that is more cost-effective than misoprostol solution and report outcomes included in this NMA. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013005116. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Cost-effectiveness of two interventions for the prevention of postpartum hemorrhage in Senegal.

OBJECTIVE: To compare, at the community level, the cost-effectiveness of oxytocin and misoprostol for the prevention of postpartum hemorrhage (PPH). METHODS: The present cost-effectiveness study used data collected during a randomized trial that compared the prophylactic effectiveness of misoprostol and oxytocin for the prevention of PPH in a rural setting in Senegal between June 6 and September 21 2013. The two interventions were compared, with referral to a higher level facility owing to PPH being the outcome measure. The costs and effects were calculated for two hypothetical cohorts of patients delivering during a 1-year period, with each cohort receiving one intervention. A comparison with a third hypothetical cohort receiving the current standard of care was included. A sensitivity analysis was performed to estimate the impact of variations in model assumptions. RESULTS: The cost per PPH referral averted was US$ 38.96 for misoprostol and US$ 119.15 for oxytocin. In all the scenarios modeled the misoprostol intervention dominated, except in the worst-case scenario, where the oxytocin intervention demonstrated slightly better cost-effectiveness. CONCLUSION: The use of misoprostol for PPH prophylaxis could be cost effective and improve maternal outcomes in low-income settings.

Prevention of postpartum haemorrhage: cost consequences analysis of misoprostol in low-resource settings.

BACKGROUND: While inferior to oxytocin injection in both efficacy and safety, orally administered misoprostol has been included in the World Health Organization Model List of Essential Medicines for use in the prevention of postpartum haemorrhage (PPH) in low-resource settings. This study evaluates the costs and health outcomes of use of oral misoprostol to prevent PPH in settings where injectable uterotonics are not available. METHODS: A cost-consequences analysis was conducted from the international health system perspective, using data from a recent Cochrane systematic review and WHO's Mother-Baby Package Costing Spreadsheet in a hypothetical cohort of 1000 births in a mixed hospital (40% births)/community setting (60% births). Costs were estimated based on 2012 US dollars. RESULTS: Using oxytocin in the hospital setting and misoprostol in the community setting in a cohort of 1000 births, instead of oxytocin (hospital setting) and no treatment (community setting), 22 cases of PPH could be prevented. Six fewer women would require additional uterotonics and four fewer women a blood transfusion. An additional 130 women would experience shivering and an extra 42 women fever. Oxytocin/misoprostol was found to be cost saving (US$320) compared to oxytocin/no treatment. If misoprostol is used in both the hospital and community setting compared with no treatment (i.e. oxytocin not available in the hospital setting), 37 cases of PPH could be prevented; ten fewer women would require additional uterotonics; and six fewer women a blood transfusion. An additional 217 women would experience shivering and 70 fever. The cost savings would be US$533. Sensitivity analyses indicate that the results are sensitive to the incidence of PPH-related outcomes, drug costs and the proportion of hospital births. CONCLUSIONS: Our findings confirm that, even though misoprostol is not the optimum choice in the prevention of PPH, misoprostol could be an effective and cost-saving choice where oxytocin is not or cannot be used due to a lack of skilled birth attendants, inadequate transport and storage facilities or where a quality assured oxytocin product is not available. These benefits need to be weighed against the large number of additional side effects such as shivering and fever, which have been described as tolerable and of short duration.

[Clinical and pharmacological study of the efficacy of carbetocin in elective caesareans compared to low and usual doses of oxytocin]. / Estudio clínico y farmacoeconómico de la eficacia de la carbetocina en cesáreas electivas respecto a la oxitocina a dosis bajas y a dosis habituales.

OBJECTIVES: To evaluate uterine contractility, bleeding, haemodynamic performance, and side effects of different doses of oxytocin after delivery under spinal anaesthesia in caesarean section without prior labour in childbirth. We also perform a pharmacoeconomic evaluation. MATERIAL AND METHODS: A randomised, descriptive, observational and multicentre prospective study was conducted, which included 104 ASA 1 patients divided into 3 groups. Group 1 (n=52) received after removal of the foetus and coinciding with foetal umbilical cord clamping, 1 IU of oxytocin followed by an infusion of 2.5 UI×h(-1); Group 2 (n=52) a continuous infusion of 20IU oxytocin at a rate of 700mUI×min(-1) followed later by 10UI×h(-1), and group 3, 100µg bolus dose of carbetocin only. RESULTS: There were no statistical differences between groups in anthropometric, obstetric or anaesthetic variables. Significant differences in uterine contraction in vaginal bleeding and the incidence of side effects, particularly headache and tremor, were more pronounced in the carbetocin group. CONCLUSIONS: With these results, we cannot recommend the routine use of carbetocin in caesarean sections, because it is accompanied by an increased incidence of side effects without any improvement in the prevention of obstetric haemorrhage. Finally, it is economically more expensive than the use of low doses of oxytocin, which may be the trend that should be considered in the future, due to the clinical outcomes, and its lower cost.

Does carbetocin for prevention of postpartum haemorrhage at caesarean section provide clinical or financial benefit compared with oxytocin?

Postpartum haemorrhage is a major cause of maternal morbidity and mortality worldwide. A recent Cochrane review of carbetocin (long-acting oxytocin analogue) concluded that its use decreased additional uterotonic requirements, however, no included studies compared its use against intravenous bolus oxytocin. The majority of studies of carbetocin have considered its use in vaginal delivery; no studies have examined the economic implications of its use. This study describes a clinical and financial evaluation undertaken at a United Kingdom District General Hospital surrounding the introduction of carbetocin for prophylaxis against postpartum haemorrhage at caesarean deliveries. A range of clinical outcomes were observed including frequency of postpartum haemorrhage, estimated blood loss, transfusion requirements, change in haemoglobin or haemodynamics, use of additional uterotonics and perioperative recovery. Finally, a composite financial analysis was performed. No clinically significant benefit was found, however associated costs increased by £18.52/patient.

Cost-effectiveness analysis of active management of third-stage labour in Vietnam.

Active management of the third stage of labour (AMTSL) using oxytocin substantially reduces postpartum haemorrhage (PPH), a leading cause of maternal mortality. An economic analysis of the use of AMTSL was conducted as part of an intervention study in Thanh Hoa Province, Vietnam. A spreadsheet was used to calculate various scenarios and estimate the costs and outcomes of the routine use of AMTSL with oxytocin in Uniject compared with oxytocin in ampoules, and AMTSL compared with no AMTSL. We estimated the health outcomes from probabilities that were generated from the effectiveness portion of the AMTSL intervention project. The study also estimates the costs of treating PPH and the net incremental costs of AMTSL (costs and savings); examines the impact of different scenarios of PPH rate and Uniject cost; and estimates the potential cost per PPH case and PPH death averted. The additional net cost per woman of providing AMTSL with ampoules was just US dollar 0.20 in the base case; using Uniject devices added only US dollar 0.08 more per woman to the ampoule cost. Varying the rate of PPH had the biggest effect; if the underlying PPH rate were 8%, the incremental cost of AMTSL drops to just US dollar 0.07 per woman with ampoules and the cost to avert a case of PPH is US dollar 2.10 with ampoules and US dollar 4.52 with Uniject. The low net incremental cost of AMTSL suggests that the introduction of AMTSL in primary-level facilities in Vietnam can reduce the incidence of PPH and benefit women's health without adding much to national health care costs.