Tratamiento médico del aborto del primer trimestre: igual eficacia, más eficiencia / Medical treatment of abortion in the first trimester: Equal effectiveness, more efficiency

Antecedentes: La pérdida gestacional precoz acontece en el 10-20% de todas las gestaciones clínicas, siendo el 85% previos a la semana 12 de amenorrea. El aborto involuntario conlleva una carga muy significativa en los recursos destinados a sanidad, alcanzado un coste económico nacional en Reino Unido de 471 millones de libras esterlinas por año (533,06 millones de euros), cifra extrapolable a otros países industrializados. Según una revisión sistemática reciente no hay ensayos bien diseñados en gestaciones del primer trimestre que arrojen una evidencia consolidada sobre cuál es el mejor método de tratamiento de aborto del primer trimestre y existen diferentes estudios que han tratado de evidenciar reducción de costes con resultados contradictorios. Material y métodos: Se realiza un estudio de diseño observacional, retrospectivo y longitudinal. Se revisaron 892 pacientes diagnosticadas de aborto espontáneo durante el primer trimestre de gestación, en el periodo comprendido entre enero de 2013 y diciembre de 2016. En nuestro estudio hemos querido evaluar la efectividad del misoprostol vaginal como tratamiento médico para el aborto espontáneo en el primer trimestre, en comparación con el legrado obstétrico/evacuador y, cuantificar la diferencia en los costos de ambos procedimientos a través de un estudio de minimización de costes. Resultados: De las 892 pacientes reclutadas, se realizó tratamiento médico con misoprostol en 517 (57,95%) y tratamiento quirúrgico mediante legrado evacuador en 375 (42,05%). La efectividad del tratamiento médico fue del 82% (426/517). Con respecto al tratamiento quirúrgico la efectividad resultó del 100%. La tasa de éxito del tratamiento médico fue superior en el subgrupo de pacientes con aborto incompleto (92,9%), en comparación con los grupos de gestación anembrionada (85,7%) y aborto diferido (78,2%). Conclusiones: El tratamiento médico del aborto es un manejo seguro y aceptado por las pacientes...(AU)

Background: Early pregnancy loss occurs in 10-20% of all clinical pregnancies, 85% being prior to week 12 of amenorrhea. Miscarriage entails a very significant burden on healthcare resources, reaching a national economic cost in the United Kingdom of £471 million per year (€533.06 million), a figure that can be extrapolated to other industrialized countries. According to a recent systematic review, there are no well-designed trials in first-trimester pregnancies that provide consolidated evidence on what is the best first-trimester abortion treatment method, and there are different studies that have tried to demonstrate cost reduction with contradictory results. Material and methods: An observational, retrospective and longitudinal design study was carried out. 892 patients diagnosed with spontaneous abortion during the first trimester of pregnancy were reviewed, in the period between January 2013 and December 2016. In our study, we wanted to evaluate the efficacy of vaginal misoprostol as a medical treatment for spontaneous abortion in the first trimester, in comparison with obstetric curettage-evacuator, and to quantify the difference in the costs of both procedures through a cost minimization study. costs. Results: Of the 892 recruited patients, medical treatment with misoprostol was performed in 517 (57.95%) and surgical treatment by curettage in 375 (42.05%). The effectiveness of medical treatment was 82% (426/517). With respect to surgical treatment the effectiveness of 100%. The success rate of medical treatment was higher in the subgroup of patients with incomplete abortion (92.9%), compared to the anembryonic gestation (85.7%) and delayed abortion (78.2%) groups. Conclusions: The medical treatment of abortion is a safe management and accepted by the patients. The adequate selection of candidate patients leads to an increase in the success rate and a decrease in costs...(AU)

Cost-effectiveness of mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage: an economic evaluation based on the MifeMiso trial.

OBJECTIVE: To assess the cost-effectiveness of mifepristone and misoprostol (MifeMiso) compared with misoprostol only for the medical management of a missed miscarriage. DESIGN: Within-trial economic evaluation and model-based analysis to set the findings in the context of the wider economic evidence for a range of comparators. Incremental costs and outcomes were calculated using nonparametric bootstrapping and reported using cost-effectiveness acceptability curves. Analyses were performed from the perspective of the UK's National Health Service (NHS). SETTING: Twenty-eight UK NHS early pregnancy units. SAMPLE: A cohort of 711 women aged 16-39 years with ultrasound evidence of a missed miscarriage. METHODS: Treatment with mifepristone and misoprostol or with matched placebo and misoprostol tablets. MAIN OUTCOME MEASURES: Cost per additional successfully managed miscarriage and quality-adjusted life years (QALYs). RESULTS: For the within-trial analysis, MifeMiso intervention resulted in an absolute effect difference of 6.6% (95% CI 0.7-12.5%) per successfully managed miscarriage and a QALYs difference of 0.04% (95% CI -0.01 to 0.1%). The average cost per successfully managed miscarriage was lower in the MifeMiso arm than in the placebo and misoprostol arm, with a cost saving of £182 (95% CI £26-£338). Hence, the MifeMiso intervention dominated the use of misoprostol alone. The model-based analysis showed that the MifeMiso intervention is preferable, compared with expectant management, and this is the current medical management strategy. However, the model-based evidence suggests that the intervention is a less effective but less costly strategy than surgical management. CONCLUSIONS: The within-trial analysis found that based on cost-effectiveness grounds, the MifeMiso intervention is likely to be recommended by decision makers for the medical management of women presenting with a missed miscarriage. TWEETABLE ABSTRACT: The combination of mifepristone and misoprostol is more effective and less costly than misoprostol alone for the management of missed miscarriages.

A Retrospective Cost-Effectiveness Analysis of Mifepristone-Misoprostol Medical Abortions in the First Year at the Regina General Hospital.

OBJECTIVE: In July 2017, mifepristone-misoprostol (mife/miso) became available for medical abortion at the Regina General Hospital's Women's Health Centre (RGH WHC). We investigated whether the proportion of abortions performed medically changed as a result of the introduction of mife/miso, whether using mife/miso instead of the surgical alternative would result in cost savings to the health care system, and whether abortion type differed between patients residing in and outside of Regina. METHODS: We conducted a retrospective chart review of all 306 medical abortions from the RGH WHC between July 1, 2017 and June 30, 2018. We obtained medical and surgical abortion information from that year and the preceding one from an administrative database. Statistical methods were used to calculate the costs of mife/miso, methotrexate-misoprostol (MTX/miso) and surgical abortion, as well as cost-effectiveness ratios. RESULTS: The proportion of medical abortions increased from 15.4% in 2016/2017 to 28.7% in 2017/2018 (χ21 = 54.629; P < 0.001). Calculated costs for mife/miso, with and without complications were CAD $1173.70 and CAD $1708.90, respectively, versus CAD $871.10 and CAD $1204.10, respectively, for MTX/miso, and CAD $1445.95 and CAD $2261.95, respectively, for hospital-based vacuum aspiration. At a willingness-to-pay threshold of CAD $318 (the cost of mife/miso), statistical modelling showed a 61.3% chance that mife/miso was more cost-effective than surgical abortion and a 90.8% chance that it was more cost-effective than MTX/miso. Patients from Regina were significantly more likely (χ21 = 29.406; P < 0.001) to receive a medical abortion (34.9% of abortions) than those living outside of Regina (19.6% of abortions). CONCLUSION: The proportion of abortions completed medically increased significantly over the period studied. Patients from Regina were more likely to receive medical abortion during both time periods. Mife/miso had a >50% probability of cost-effectiveness over both surgical and MTX/miso options.

Cost of goods sold analysis and recommendations to reduce costs of co-packaged mifepristone-misoprostol for medical abortion.

OBJECTIVE: Understanding the price components of the mifepristone/misoprostol (combi-pack) for medical abortion to improve access is critical for identifying strategies to reduce product costs for quality-assured formulations and expanding its availability and use. METHODS: We constructed a cost of goods sold analysis using data collected from manufacturing companies in Bangladesh, China and India supported by publicly available information related to the product formulation, active pharmaceutical ingredients (API), manufacturing location, manufacturer profiles and other individual model components. Key model components were the active pharmaceutical ingredients (quality-assured or not), excipients, labour cost, operating cost and packaging. RESULTS: Combi-pack direct production cost ranges from US$1.08 for finished products which are not quality assured to US$3.05 for products containing quality assured active pharmaceutical ingredients, which means that with a 30% administrative fee applied to those prices, it could be made available between US$1.40 and US$3.97 depending on location, manufacturer's profile, optimal market situation and the quality of the active pharmaceutical ingredients. The main model component impacting on the cost range is the purchase price of mifepristone active pharmaceutical ingredient and the current differential between quality-assured material supported by adequate documentation and API for which quality assurance cannot be demonstrated. Compared to India cost of goods sold is lower in Bangladesh primarily due to lower operating costs, including the cost of labour. CONCLUSIONS: It is feasible to lower the cost of quality-assured combi-packs, through reducing mifepristone API cost and selection of the manufacturing location. However, manufacturers need to be incentivised to achieve WHO pre-qualification with a carefully built business case and require support in identifying and sourcing competitively priced material and manufacturing products to the necessary standard.

Online Abortion Drug Sales in Indonesia: A Quality of Care Assessment.

This study sought to understand the experience of buying misoprostol online for pregnancy termination in Indonesia. We conducted a mystery client study August through October, 2019. Interactions were analyzed quantitatively and qualitatively, along with the contents of the packages. One hundred ten sellers were contacted, from whom mystery clients made 76 purchases and received 64 drug packages. Almost all sellers sold "packets" containing multiple drugs; 73 percent of packets contained misoprostol, and 47 percent contained at least 800 mcg of misoprostol. Thirty-four packets contained insufficient drugs to complete an abortion. When compared to WHO standards, 87 percent of sellers imparted incomplete information about potential physical effects; no seller provided information about possible complications. Women buying misoprostol from informal online drugs sellers will be underprepared for understanding potential side effects and complications. Educational activities are needed to increase women's access to information about safe use of misoprostol as a harm reduction strategy.

Mifepristone Combination Therapy Compared With Misoprostol Monotherapy for the Management of Miscarriage: A Cost-Effectiveness Analysis.

OBJECTIVE: To assess whether mifepristone pretreatment adversely affects the cost of medical management of miscarriage. METHODS: Decision tree analyses were constructed, and Monte Carlo simulations were run comparing costs of combination therapy (mifepristone and misoprostol) with monotherapy (misoprostol alone) for medical management of miscarriage in multiple scenarios weighing clinical practice, patient income, and surgical evacuation modalities for failed medical management. Rates of completed medical evacuation for each were obtained from a recent randomized controlled trial. RESULTS: In every scenario, combination therapy offered a significant cost advantage over monotherapy. Using a Monte Carlo analysis, cost differences favoring combination therapy ranged from 6.3% to 19.5% in patients making federal minimum wage. The cost savings associated with combination therapy were greatest in scenarios using a staged approach to misoprostol administration and in scenarios using in-operating room dilation and curettage as the only modality for uterine evacuation, a savings of $190.20 (99% CI 189.35-191.07) and $217.85 (99% CI 217.19-218.50) per patient in a low-income wage group, respectively. A smaller difference was seen in scenarios using in-office manual vacuum aspiration to complete medical management failures. As patients' wages increased, the difference in cost between combination therapy and monotherapy increased. CONCLUSION: Mifepristone combined with misoprostol is, overall, more cost effective than monotherapy, and therefore cost should not be a deterrent to its adoption in the management of miscarriage.

Cost-effectiveness of Mifepristone Pretreatment for the Medical Management of Nonviable Early Pregnancy: Secondary Analysis of a Randomized Clinical Trial.

Importance: Early pregnancy loss (EPL) is the most common complication of pregnancy. A multicenter randomized clinical trial compared 2 strategies for medical management and found that mifepristone pretreatment is 25% more effective than the standard of care, misoprostol alone. The cost of mifepristone may be a barrier to implementation of the regimen. Objective: To assess the cost-effectiveness of medical management of EPL with mifepristone pretreatment plus misoprostol vs misoprostol alone in the United States. Design, Setting, and Participants: This preplanned. prospective economic evaluation was performed concurrently with a randomized clinical trial in 3 US sites from May 1, 2014, through April 30, 2017. Participants included 300 women with anembryonic gestation or embryonic or fetal demise. Cost-effectiveness was computed from the health care sector and societal perspectives, with a 30-day time horizon. Data were analyzed from July 1, 2018, to July 3, 2019. Interventions: Mifepristone pretreatment plus misoprostol administration vs misoprostol alone. Main Outcomes and Measures: Costs in 2018 US dollars, effectiveness in quality-adjusted life-years (QALYs), and treatment efficacy. Incremental cost-effectiveness ratios (ICERs) of mifepristone and misoprostol vs misoprostol alone were calculated, and cost-effectiveness acceptability curves were generated. Results: Among the 300 women included in the randomized clinical trial (mean [SD] age, 30.4 [6.2] years), mean costs were similar for groups receiving mifepristone pretreatment and misoprostol alone from the health care sector perspective ($696.75 [95% CI, $591.88-$801.62] vs $690.88 [95% CI, $562.38-$819.38]; P = .94) and the societal perspective ($3846.30 [95% CI, $2783.01-$4909.58] vs $4845.62 [95% CI, $3186.84-$6504.41]; P = .32). The mifepristone pretreatment group had higher QALYs (0.0820 [95% CI, 0.0815-0.0825] vs 0.0806 [95% CI, 0.0800-0.0812]; P = .001) and a higher completion rate after first treatment (83.8% vs 67.1%; P < .001) than the group receiving misoprostol alone. From the health care sector perspective, mifepristone pretreatment was cost-effective relative to misoprostol alone with an ICER of $4225.43 (95% CI, -$195 053.30 to $367 625.10) per QALY gained. From the societal perspective, mifepristone pretreatment dominated misoprostol alone (95% CI, -$5 111 629 to $1 801 384). The probabilities that mifepristone pretreatment was cost-effective compared with misoprostol alone at a willingness-to-pay of $150 000 per QALY gained from the health care sector and societal perspectives were approximately 90% and 80%, respectively. Conclusions and Relevance: This study found that medical management of EPL with mifepristone pretreatment was cost-effective when compared with misoprostol alone. Trial Registration: ClinicalTrials.gov Identifier: NCT02012491.

Stocking and over-the-counter sale of misoprostol for medical abortion in Ghana's community pharmacies: comparison of questionnaire and mystery client survey.

OBJECTIVES: In many sub-Saharan African countries with restricted safe abortion services, community pharmacies are important sources of abortifacients. However, data on stocking and over-the-counter sale of abortifacients in community pharmacies are often limited. The main objective of this study was to compare stocking and over-the-counter sale of misoprostol at community pharmacies using questionnaire and mystery client surveys in Ghana. METHODS: A cross-sectional questionnaire-based survey, complemented with a mystery client survey, was conducted at 165 randomly selected community pharmacies in Accra, Ghana. Structured questionnaires were administered to pharmacists/pharmacy workers. A mystery client survey to each of these pharmacies was also undertaken. Descriptive statistical techniques (frequencies and proportions) were used to estimate and compare stocking and over-the-counter sale of misoprostol at community pharmacies from the two data collection methods. KEY FINDINGS: Some 50.3% (83) of community pharmacists/pharmacy workers reported stocking misoprostol and selling it over-the-counter for medical abortion in the questionnaire-based survey. However, in the mystery client survey, 122 (74%) pharmacists/pharmacy workers reported stocking misoprostol and actually selling it over-the-counter to the mystery clients. Thus approximately 39 (24%) more pharmacies stocked misoprostol and sold it over-the-counter even though they originally denied stocking the drug in the questionnaire survey. Also, the drug was often sold without a prescription, and many did so without asking for a confirmatory pregnancy test or gestational age. CONCLUSIONS: In contexts where access to safe abortion services is restricted, mystery client surveys, rather than conventional questionnaire-based survey techniques, may better illuminate stocking and over-the-counter sale of abortifacients at community pharmacies.

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.

Medical versus surgical treatment of first trimester spontaneous abortion: A cost-minimization analysis.

BACKGROUND: Traditionally the gold-standard technique for the treatment of spontaneous abortion has been uterine evacuation by aspiration curettage. However, many studies have proposed medical treatment with misoprostol as an alternative to the conventional surgical treatment. The aim of this study was to apply cost minimization methods to compare the cost and effectiveness of the use of vaginal misoprostol as a medical treatment for first trimester spontaneous abortion with those of evacuation curettage as a surgical treatment. METHODOLOGY/PRINCIPAL FINDINGS: We present a longitudinal, prospective and quasi-experimental research study including a total of 547 patients diagnosed with first-trimester spontaneous abortion, in the period from January 2013 to December 2015. Patients were offered medical treatment with 800 mg vaginal misoprostol or evacuation curettage. Patients treated with misoprostol were followed-up at 7 days and a transvaginal ultrasound was performed to confirm the success of the treatment. If it failed, a second dose of 800 mg of vaginal misoprostol was prescribed and a new control ultrasound was performed. In case of failure of medical treatment after the second dose of misoprostol, evacuation curettage was indicated. The effectiveness of each of the treatment options was calculated using a decision tree. The cost minimization study was carried out by weighting each cost according to the effectiveness of each branch of the treatment. Of the 547 patients who participated in the study, 348 (64%) chose medical treatment and 199 (36%) chose surgical treatment. The overall effectiveness of medical treatment was 81% (283/348) and surgical treatment of 100%. The estimated final cost for medical treatment was € 461.92 compared to € 2038.72 for surgical treatment, which represents an estimated average saving per patient of € 1576.8. CONCLUSIONS/SIGNIFICANCE: Medical treatment with misoprostol is a cheaper alternative to surgery: in the Spanish Public Healthcare System, it is five times more inexpensive than curettage. Given its success rates higher than 80%, mild side effects, controllable with additional medication and the high degree of overall satisfaction, it should be prioritized over the evacuation curettage in patients who meet the treatment criteria.

The costs and cost effectiveness of providing second-trimester medical and surgical safe abortion services in Western Cape Province, South Africa.

BACKGROUND: In South Africa, access to second-trimester abortion services, which are generally performed using medical induction with misoprostol alone, is challenging for many women. We aimed to estimate the costs and cost effectiveness of providing three safe second-trimester abortion services (dilation and evacuation (D&E)), medical induction with mifepristone and misoprostol (MI-combined), or medical induction with misoprostol alone (MI-misoprostol)) in Western Cape Province, South Africa to aid policymakers with planning for service provision in South Africa and similar settings. METHODS: We derived clinical outcomes data for this economic evaluation from two previously conducted clinical studies. In 2013-2014, we collected cost data from three public hospitals where the studies took place. We collected cost data from the health service perspective through micro-costing activities, including discussions with site staff. We used decision tree analysis to estimate average costs per patient interaction (e.g. first visit, procedure visit, etc.), the total average cost per procedure, and cost-effectiveness in terms of the cost per complete abortion. We discounted equipment costs at 3%, and present the results in 2015 US dollars. RESULTS: D&E services were the least costly and the most cost-effective at $91.17 per complete abortion. MI-combined was also less costly and more cost-effective (at $298.03 per complete abortion) than MI-misoprostol (at $375.31 per complete abortion), in part due to a shortened inpatient stay. However, an overlap in the plausible cost ranges for the two medical procedures suggests that the two may have equivalent costs in some circumstances. CONCLUSION: D&E was most cost-effective in this analysis. However, due to resistance from health care providers and other barriers, these services are not widely available and scale-up is challenging. Given South Africa's reliance on medical induction, switching to the combined regimen could result in greater access to second-trimester services due to shorter inpatient stays without increasing costs.

Foley catheter vs. oral misoprostol to induce labour among hypertensive women in India: a cost-consequence analysis alongside a clinical trial.

OBJECTIVE: To determine the effectiveness and economic impact of two methods for induction of labour in hypertensive women, in low-resource settings. DESIGN: Cost-consequence analysis of a previously reported multicentre, parallel, open-label randomised trial. SETTING & POPULATION: A total of 602 women with a live fetus, aged ≥18 years requiring delivery for pre-eclampsia or hypertension, in two public hospitals in Nagpur, India. METHODS: We performed a formal economic evaluation alongside the INFORM clinical trial. Women were randomised to receive transcervical Foley catheterisation or oral misoprostol 25 mcg. Healthcare expenditure was calculated using a provider-side microcosting approach. MAIN OUTCOME MEASURES: Rates of vaginal this delivery within 24 hours of induction, healthcare expenditure per completed treatment episode. RESULTS: Induction with oral misoprostol resulted in a (mean difference) $20.6USD reduction in healthcare expenditure [95% CI (-) $123.59 (-) $72.49], and improved achievement of vaginal delivery within 24 hours of induction, mean difference 10% [95% CI (-2 to 17.9%), P = 0.016]. Oxytocin administration time was reduced by 135.3 minutes [95% CI (84.4-186.2 minutes), P < 0.01] and caesarean sections by 9.1% [95% CI (1.1-17%), P = 0.025] for those receiving oral misoprostol. Following probabilistic sensitivity analysis, oral misoprostol was cost-saving in 63% of 5,000 bootstrap replications and achieved superior rates of vaginal delivery, delivery within 24 hours of induction and vaginal delivery within 24 hours of induction in 98.7%, 90.7%, and 99.4% of bootstrap simulations. Based on univariate threshold analysis, the unit price of oral misoprostol 25 mcg could feasibly increase 31-fold from $0.24 to $7.50 per 25 mcg tablet and remain cost-saving. CONCLUSION: Compared to Foley catheterisation for the induction of high-risk hypertensive women, oral misoprostol improves rates of vaginal delivery within 24 hours of induction and may also reduce costs. Additional research performed in other low-resource settings is required to determine their relative cost-effectiveness. TWEETABLE ABSTRACT: Oral misoprostol less costly and more effective than Foley catheter for labour induction in hypertension.

Exploring the feasibility of obtaining mifepristone and misoprostol from the internet.

OBJECTIVES: We aimed to document the experience of buying abortion pills from online vendors that do not require a prescription and to evaluate the active ingredient content of the pills received. STUDY DESIGN: We searched the internet to identify a convenience sample of websites that sold mifepristone and misoprostol to purchasers in the United States and attempted to order these products. We documented price, shipping time and other aspects of ordering. We sent the samples received to a testing laboratory that measured the amount of active ingredient in individual tablets. RESULTS: We identified 18 websites and ordered 22 products: 20 mifepristone-misoprostol combination products and 2 that contained only misoprostol. We received 18 combination products and the 2 misoprostol products from 16 different sites. No site required a prescription or any relevant medical information. The time between order and receipt of the 20 products ranged from 3 to 21 business days (median 9.5 days). The price for the 18 combination products ranged from $110 to $360, including shipping and fees; the products without mifepristone cost less. Chemical assays found that the 18 tablets labeled 200 mg mifepristone contained between 184.3 mg and 204.1 mg mifepristone, while the 20 tablets labeled 200 mcg misoprostol contained between 34.1 mcg and 201.4 mcg of the active ingredient. CONCLUSIONS: Obtaining abortion medications from online pharmaceutical websites is feasible in the United States. The mifepristone tablets received contained within 8% of the labeled amount of active agent. The misoprostol tablets all contained that compound but usually less than labeled. IMPLICATIONS STATEMENT: Given our findings, we expect that some people for whom clinic-based abortion is not easily available or acceptable may consider self-sourcing pills from the internet to be a rational option.

What can we do to reduce the associated costs in induction of labour of intrauterine growth restriction foetuses at term? A cost-analysis study.

OBJECTIVE: To evaluate the costs associated with induction of labour in intrauterine growth restriction fetuses comparing different procedures. STUDY DESIGN: 150 pregnancies at term diagnosed with intrauterine growth restriction and indication for induction of labour were included. 24 were ripened with misoprostol 25 µg tablets, 24 with dinoprostone 10 mg vaginal insert, and 77 with Cook® cervical ripening balloon. To determine the costs of induction of labour, method of induction, intrapartum medication, epidural analgesia, type of delivery, and maternal and neonatal admissions were considered. Statistical analysis was performed using the G-Stat 2.0 free statistical software. ANOVA test was used for comparisons between quantitative parametric variables. Chi-squared test or Fisher test was used for qualitative variables. A value of p < 0.05 was considered statistically significant. RESULTS: Up to 70.83% women in dinoprostone group gave birth within the first 24 h compared to 42.66% in misoprostol group and 36.36% in CG (p < 0.01). Misoprostol tablets were cheaper (9.45 ± 1.52 US dollars) than dinoprostone or Cook® balloon (41.67 ± 0 and 59.85 ± 0 54.45 ± 0 US dollars, respectively) (p < 0.01). Costs related to maternal admissions were higher in CG (475.13 ± 146.95$) than dinoprostone group (475.13 ± 146.95$) or MG (427.97 ± 112.65$) (p = 0.03). Total costs in misoprostol group (2765.18 ± 495.38$) were lower than in the dinoprostone group (3075.774 ± 896.14$) or Cook® balloon group (3228.02 ± 902.06$) groups. CONCLUSIONS: Misoprostol for induction of labour had lower related costs than dinoprostone or Cook® balloon, with similar obstetrical and perinatal outcomes.

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.

Update on second-trimester surgical abortion.

PURPOSE OF REVIEW: To review the recent literature on surgical second-trimester abortion, with specific attention to cervical preparation techniques. RECENT FINDINGS: Confirming previous studies, a recent retrospective observational cohort study, including 54 911 abortions, estimated the total abortion-related complication rate to be 0.41% for second-trimester or later procedures. Cervical preparation is known to reduce risks associated with second-trimester dilation and evacuation (D&E). When considering adjuncts to osmotic dilators for cervical preparation prior to D&E after 16 weeks, both misoprostol and mifepristone are effective alone and in combination or as adjuncts to osmotic dilators. Misoprostol consistently has been shown to cause more pain and cramping than placebo, but is an effective adjunct to osmotic dilators after 16 weeks. Although mifepristone has fewer side-effects, at its current price, it may not be as cost-effective as misoprostol. SUMMARY: Second-trimester abortion is safe. The use of mifepristone and misoprostol for second-trimester abortion has improved safety and efficacy of medical and surgical methods when used alone or in combination and as adjuncts to osmotic dilators. An important aspect of D&E, cervical preparation, is not a one-size-fits-all practice; the approach and methods are contingent on patient, provider and setting and should consider all the evidence-based options.

Misoprostol Vaginal Insert in Labor Induction: A Cost-Consequences Model for 5 European Countries-An Economic Evaluation Supported with Literature Review and Retrospective Data Collection.

INTRODUCTION: The present study aimed to assess the costs and consequences of using an innovative medical technology, misoprostol vaginal insert (MVI), for the induction of labor (IOL), in place of alternative technologies used as a standard of care. METHODS: This was a retrospective study on cost and resource utilization connected with economic model development. Target population were women with an unfavorable cervix, from 36 weeks of gestation, for whom IOL is clinically indicated. Data on costs and resources was gathered via a dedicated questionnaire, delivered to clinical experts in five EU countries. The five countries participating in the project and providing completed questionnaires were Austria, Poland, Romania, Russia and Slovakia. A targeted literature review in Medline and Cochrane was conducted to identify randomized clinical trials meeting inclusion criteria and to obtain relative effectiveness data on MVI and the alternative technologies. A hospital perspective was considered as most relevant for the study. The economic model was developed to connect data on clinical effectiveness and safety from randomized clinical trials with real life data from local clinical practice. RESULTS: The use of MVI in most scenarios was related to a reduced consumption of hospital staff time and reduced length of patients' stay in hospital wards, leading to lower total costs with MVI when compared to local comparators. CONCLUSIONS: IOL with the use of MVI generated savings from a hospital perspective in most countries and scenarios, in comparison to alternative technologies. FUNDING: Sponsorship, article processing charges, and the open access charge for this study were funded by Ferring Pharmaceuticals Poland.

Impacto del cambio de fármaco utilizado en la inducción del parto: misoprostol vaginal versus dinoprostona / Impact of changing the drug used in induction of labor: vaginal misoprostol versus dinoprostone

Objetivo: comparar la eficacia, seguridad y coste de dos pautas para la maduración cervical en la inducción del parto: misoprostol vaginal versus dinoprostona. Sujetos y método: comparación retrospectiva de dos cohortes de pacientes ingresadas en el primer y segundo semestre de 2013 (90 pacientes tratadas con dinoprostona y 89 con misoprostol). Resultados: no hemos encontrado diferencias estadísticamente significativas en cuanto al tipo de parto, ni el tiempo hasta el parto vaginal, tampoco en los resultados perinatales. Se ha objetivado menor necesidad de uso de oxitocina y una menor necesidad de retirada de la medicación o uso de tocólisis en el grupo de misoprostol. El coste ha sido menor con el uso de misoprostol. Conclusiones: el misoprostol es un fármaco eficaz, equiparable a la dinoprostona en los casos seleccionados, con mejor perfil de seguridad y más económico (AU)

Objetive: To compare the efficacy, safety and cost of two different methods for cervical priming before induction vaginal misoprostol vs. dinoprostone Material and methods: Retrospective cohort study in two groups of patients: 90 patients (group 1) with dinoprostone and 89 patients (group 2) with misoprostol. Results: No significant differences were found in the route of delivery, mean time to vaginal delivery, or neonatal outcomes. The misoprostol group had significantly lower oxytocin infusion requirements and less need for removal of vaginal medication or tocolysis. The cost was also lower with the use of misoprostol Conclusions: Misoprostol is an effective drug, similar to dinoprostone in selected patients, and is safer and more cost-effective (AU)

Medical Abortion Provided by Nurse-Midwives or Physicians in a High Resource Setting: A Cost-Effectiveness Analysis.

OBJECTIVE: The objective of the present study is to calculate the cost-effectiveness of early medical abortion performed by nurse-midwifes in comparison to physicians in a high resource setting where ultrasound dating is part of the protocol. Non-physician health care professionals have previously been shown to provide medical abortion as effectively and safely as physicians, but the cost-effectiveness of such task shifting remains to be established. STUDY DESIGN: A cost effectiveness analysis was conducted based on data from a previously published randomized-controlled equivalence study including 1180 healthy women randomized to the standard procedure, early medical abortion provided by physicians, or the intervention, provision by nurse-midwifes. A 1.6% risk difference for efficacy defined as complete abortion without surgical interventions in favor of midwife provision was established which means that for every 100 procedures, the intervention treatment resulted in 1.6 fewer incomplete abortions needing surgical intervention than the standard treatment. The average direct and indirect costs and the incremental cost-effectiveness ratio (ICER) were calculated. The study was conducted at a university hospital in Stockholm, Sweden. RESULTS: The average direct costs per procedure were EUR 45 for the intervention compared to EUR 58.3 for the standard procedure. Both the cost and the efficacy of the intervention were superior to the standard treatment resulting in a negative ICER at EUR -831 based on direct costs and EUR -1769 considering total costs per surgical intervention avoided. CONCLUSION: Early medical abortion provided by nurse-midwives is more cost-effective than provision by physicians. This evidence provides clinicians and decision makers with an important tool that may influence policy and clinical practice and eventually increase numbers of abortion providers and reduce one barrier to women's access to safe abortion.

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.