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Cost-effectiveness and Budget Impact of Introducing Heat-stable Carbetocin for Postpartum Hemorrhage Prevention in Nigeria
*Corresponding author: Olatunde Ayodele Amode, Sexual Reproductive, Maternal and Newborn Care, and Family Planning Program, Clinton Health Access Initiative Nigeria, Minna, Nigeria. oamode@clintonhealthaccess.org;
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Received: ,
Accepted: ,
How to cite this article: Amode OA, Oyedele DK, Salele H, Adekeye O, Igbokwe U, Ameyan L, et al. Cost-effectiveness and budget impact of introducing heat-stable carbetocin for postpartum hemorrhage prevention in Nigeria. Int J Matern Child Health AIDS. 2025. 2025;14:e025. doi: 10.25259/IJMA_51_2024
Abstract
Background and Objective:
Nigeria accounts for about 28.5% of the global maternal death burden, with 22% of these deaths caused by postpartum hemorrhage (PPH). The high prevalence of poor-quality uterotonics, particularly oxytocin and misoprostol, results in more PPH cases. Heat-stable carbetocin (HSC), a thermo-stable analog of oxytocin, is a suitable uterotonic option for preventing PPH, particularly in regions like Nigeria where the quality of oxytocin, the “gold standard uterotonic, ” cannot be assured.
Methods:
This evaluation assesses the cost-effectiveness, budget, and health impacts of introducing HSC compared to current prophylactic standards for PPH prevention among women delivering in public healthcare facilities in Nigeria. Quantitative data on direct healthcare system costs of using oxytocin, misoprostol, oxytocin– misoprostol combination, and HSC to prevent PPH collected from one state in each of six geopolitical zones in Nigeria served as inputs into a hierarchical decision-tree model built to generate public healthcare system perspective outputs on related PPH deaths and disabilities (disability-adjusted life-years), budget impact, and cost-effectiveness.
Results:
In a cohort of 2,548,136 deliveries, HSC may avert 111,652 PPH events when compared against oxytocin. This includes 12,873 PPH cases, 31,442 severe morbidities (disability-adjusted life years), and 1,165 deaths. These are associated with a 6% reduction in total cost to the health system and cost per woman, respectively. The budget impact analysis revealed a possible total cumulative savings to the public healthcare system of ₦352,798,943 (USD $ 235,199) if HSC is scaled up over 5 years to a 17% market share of prophylactic uterotonics administered.
Conclusion and Global Health Implications:
Introducing HSC for PPH prevention may be a cost-effective public health intervention in Nigeria when compared to oxytocin, the current standard of care to prevent PPH. Health-economic modeling projects HSC to be associated with lower costs to the health system while conferring better maternal health outcomes when compared to oxytocin or oxytocin–misoprostol combination.
Keywords
Cost-Effectiveness Analysis
Economic Evaluation
Heat-stable Carbetocin
Postpartum Hemorrhage
Uterotonics
INTRODUCTION
Background to the Study
Nigeria has the highest number of maternal deaths worldwide, with 82,000 (28.5%) deaths annually.[1] The country’s maternal mortality ratio (MMR) is 1,047 deaths for every 100,000 live births, meaning 1 in 5 Nigerian women is at a high risk of death during pregnancy.[1] Postpartum hemorrhage (PPH) remains the leading cause of maternal deaths, accounting for approximately 22% of these fatalities.[1,2] Progress towards attaining the Sustainable Development Goal (SDG) target of a global average of <70 maternal deaths per 100,000 live births, and <140 maternal deaths per 100,000 live births for Nigeria, remains painfully slow.[3]
A high proportion of mortalities and morbidities associated with PPH can be prevented with simple interventions such as prompt and consistent administration of good-quality uterotonics to address uterine atony, which causes 70% of PPH cases in Nigeria.[4] Oxytocin, the gold standard uterotonic, and misoprostol are the most commonly used for PPH prevention in Nigeria.[5]
Oxytocin must be stored and transported at 2–8°C, and misoprostol quickly degrades when exposed to humidity.[6] According to Anyakora et al., 74.5% of oxytocin and 33% of misoprostol tested from healthcare facilities and pharmaceutical outlets were found to be of sub-optimal quality.[7] Ejekam et al., found that only 52% of the 705 healthcare workers were aware that oxytocin should be stored at 2°C–8°C; 41% reported using 20 international unit (IU) and 10%, 30 IU–60 IU oxytocin for PPH prevention – dosing that is higher than the recommended prophylactic dose, and 13% of respondents thought that most oxytocin brands in use were ineffective.[8]
Investment in the supply of maternal and newborn health commodities by national and sub-national governments, funding and implementing partners, and the private sector is determined by factors such as financing, cost, quality, safety, effectiveness, and affordability. Cost, a key determinant of demand and supply-side cost-effectiveness thresholds, is affected by the availability of substitute medicines and product quality.[9] Availability of good quality maternal and newborn medicines is important to achieving the 2030 agenda.[10]
In 2018, the World Health Organization updated its recommendations on uterotonics for the prevention of PPH[11] based on a meta-analysis of 196 trials involving 135,559 women across 53 high-, middle-, and low-income countries. The study found that the ergometrine–oxytocin combination, oxytocin–misoprostol combination, and carbetocin are more effective than oxytocin and misoprostol for preventing PPH (≥500 mL of blood loss). While the two-combination therapies have significant side effects, the safety profile of carbetocin was similar to oxytocin.[5,12]
While previous cost-effectiveness studies on uterotonics focused on oxytocin and misoprostol,[13] this study evaluates the effectiveness of heat-stable carbetocin (HSC) for preventing PPH compared to commonly used uterotonics like oxytocin and misoprostol, and oxytocin–misoprostol combination. These and ergometrine are the common uterotonics for PPH management in Nigeria.[14] Using a predictive health economics model, we explored the business case for potential HSC introduction in Nigeria, demonstrating the cost-effectiveness and budget impact compared to oxytocin, misoprostol, and oxytocin– misoprostol combination in public facilities. The findings are essential for policymakers, government officials, funders, and health insurance schemes as they consider prioritization and inclusion of HSC in public health programming.
Study Aim
This study aims to determine the relative cost-effectiveness (clinical outcomes and associated costs) and budget impact of HSC compared with the current standard of care uterotonics for PPH prevention in Nigeria.
METHODS
Study Design and Participants
This health-economic evaluation analyzes the cost-effectiveness and budget impact of using uterotonics for PPH prevention in public health facilities. A decision-analytic model was used, targeted for low- and middle-income countries. Data were collected using a structured questionnaire across six Nigerian states: Kano, Lagos, Niger, Imo, Rivers, and Yobe, with one state selected from each geopolitical zone based on the high burden of maternal mortality relative to other states in their regions, and the high probability of early adoption for innovations [Figure 1]. Participants included clinicians from three public healthcare facilities (tertiary, secondary, and primary), Heads of billing/administration units in secondary and tertiary healthcare facilities, directors of finance and administration at the state ministries of health, primary healthcare (PHC) boards/agencies, drug management agencies, and hospital management boards. Private clinics and clinicians outside the field of obstetric care were excluded from the study. All study participants provided informed consent.
- Map of Nigeria showing the states where the study was conducted.
Decision-Tree Model Algorithm
The decision-tree model [Figure 2] compared outcome measures between HSC and three other uterotonics in use for PPH prevention: Oxytocin, misoprostol, and oxytocin–misoprostol combination during deliveries either through the vaginal or abdominal (cesarean section) route.
- The hierarchical decision tree model.
Definitions
PPH
The occurrence of PPH is defined as blood loss from the genital tract of ≥500 mL following delivery.[15] This model classifies PPH into mild/moderate (500 mL–1,000 mL of blood loss) and severe (≥1,000 mL of blood loss). Women who undergo cesarean sections and those with severe anemia are considered at higher risk of experiencing PPH and its associated complications, and the treatment setting, as captured by the model – primary, secondary, or tertiary level – significantly determines health outcomes related to PPH.
Cost-effectiveness
Cost-effectiveness refers to the comparison of the relative costs and effects of using HSC compared to oxytocin, misoprostol, and oxytocin–misoprostol combination for PPH prevention. Measured costs included direct costs to the health care system, and measured outcomes were cases averted and disability-adjusted life years (DALYs).
Budget impact
Specific to budget impact, defined as the total direct financial cost of introducing and incremental scaling-up HSC to 17% of the uterotonic market share over 5 years (2024–2028). We modeled the gradual introduction of HSC into the available uterotonic accessible to the birthing cohort of 2,548,136 (1,019,254 in primary, 637,034 in secondary, and 891,848 in tertiary healthcare treatment settings) as reported in the district health information software-2 (DHIS2) 2019. Undergoing vaginal and cesarean births. With the base model input showing that oxytocin, accounted for 65%, misoprostol 11.5% and oxytocin–misoprostol combination 23.5% of prophylactic uterotonics use, and with a yearly increase in the proportion of HSC use for PPH prevention from 3 to 5% (2025) up to a maximum of 17% by 2028, with current decrease in the proportion of the other uterotonics in the health benefits package in Nigeria to 54.5%, 9%, and 19.5%, respectively.
Model Inputs
Primary and secondary data were used in a model examining the cost-effectiveness of uterotonics for the prevention of PPH in India.[16] Model parameters were from published literature, expert opinions, local costing, and health facility utilization data. Data collection using structured questionnaires was conducted through a scoping exercise that included interviews with 84 key opinion leaders (KOLs), including doctors [obstetricians and non-specialist doctors], nurses, midwives, pharmacists, and administrators, all of whom provided informed consent. Secondary data sources included the Nigerian Demographic and Health Survey 2018 (NDHS 2018)[17] and the DHIS2.[18] along with information collected from Internet searches for articles, meta-analyses, and systematic reviews. All collected information was anonymized and coded, with data entry on Excel sheets stored securely by authorized interviewers and evaluation staff.
Data collected were summarized into weighted averages to produce nationally representative data categorized as general inputs (population, healthcare setting), clinical inputs (uterotonic dosing, efficacy, PPH management, disability, mortality risk), and economical inputs (drug and drug administration costs, healthcare resource use, cold-chain costs).
Population and delivery characteristics
We analyzed the distribution of facility-based births across the three healthcare settings nationwide. Of all deliveries, 40% occur at the PHC level, 25% at the secondary health care level, and 35% at the tertiary health care level. We obtained aggregate indicators, such as the proportion of institutional births and births in public facilities, from the NDHS and DHIS2.[17,18] Anemia rates collected from different tiers range between 60 and 67%,[19] as shown in Table 1.
| Variable | Value | Source |
|---|---|---|
| Total cohort size | 2,548,136 | DHIS2 Data - 2019 |
| Distribution of women giving birth per healthcare setting (%) | PHC: 40 | DHIS2 Data -2019 |
| SHF: 25 | ||
| THF: 35 | ||
| Percentage of women with anemia per healthcare setting | PHC: 60 | NDHS 2018 |
| SHF: 63 | ||
| THF: 67 | ||
| Percentage of women with secondary infections after SVD | PHC: 0 | KOL |
| SHF: 4 | ||
| THF: 5 | ||
| Percentage of women with secondary infections after C-section deliveries | PHC: 0 | KOL |
| SHF: 12 | ||
| THF: 12 | ||
| Proportion of C-section births (%) | 6 | DHIS2 Data - 2019 |
| MMR | 1047 | WHO 2023. Trends in maternal mortality 2000–2020: estimates by the WHO, UNICEF, UNFPA, World Bank group and the United Nations Population Division; Annex 4 |
| PPH-related mortality as a percentage of MMR | 22 | Federal Ministry of Health, Nigeria, 2019. Roadmap for the Accelerated Reduction of Maternal and Neonatal Mortality. |
| Willingness-to-pay threshold (in local currency) | ₦3,233,297 | World Bank Data (2019) CBN Exchange rate |
₦: Naira (Nigerian), DHIS2: District health information software-2, PHC: Primary health care, SHF: Secondary health facility, THF: Tertiary health facility, NDHS: Nigerian demographic and health survey, KOL: Key opinion leader, SVD: Spontaneous vaginal delivery, MM%ternal mortality ratio, PPH: Postpartum hemorrhage, WHO: World Health Organization, UNICEF: United nations children’s fund, UNFPA: United nations population fund, CBN: Central bank of Nigeria, C-section: Cesarean section
Efficacy of prophylactic uterotonics
Model input data on uterotonic efficacy were from the 2018 Cochrane Uterotonic Network Meta-Analysis, which ranked uterotonics for the prevention of PPH using data from 197 trials.[5]
Risk of mortality
For the risk of mortality due to PPH, we considered differences in healthcare settings and degree of anemia; Nyfløt et al. show that severe anemia is associated with a high risk of PPH at an odds ratio of 4.27 (95% confidence interval: 2.79–6.54).[20] Data input of MMR of 1,047 and the percentage of death resulting from PPH 22% are from the NDHS 2018, recent trends in maternal mortality[1,16] and the Nigerian Federal Ministry of Health Roadmap for the Accelerated Reduction of maternal and neonatal mortality 2019.[21]
Disability
The disability measure DALYs were employed for use in the model, with data from the Global Burden of Disease study and a study by Lubinga et al. used as inputs for disability weights and outcome measures.[13,22] The non-availability of related quality-adjusted life years prevented its use as a measure of disability in this study.
Healthcare resources use and costs
Clinical details on uterotonic administration were obtained from KOLs across primary, secondary, and tertiary healthcare facilities. This included information on healthcare resource use and drug and administration costs. Table 2 outlines the inputs affecting the cost of PPH care. Other costs considered in the model include the average salaries of healthcare providers, referral costs, the cost of a 1-day hospital stay, and follow-up expenses.
| Cost items | Heat-stablecarbetocin | Oxytocin | Misoprostol | Oxytocin±misoprostol |
|---|---|---|---|---|
| Drug dosage (Prevention) | 100 µg | 10 IU | 600 µg | 10 IU/600 µg |
| Cost per vial/tablet (in naira) | 1,450 | 465 | 120 | 465/120 |
| Cost per dose (in naira) | 1,450 | 465 | 360 | 825 |
| Proportion of women requiring additional uterotonics (vaginal births) (%) | 5.2 | 11.6 | 12.1 | 6.6 |
| Proportion of women requiring additional uterotonics (C-section births) (%) | 13.7 | 30.4 | 31.6 | 17.3 |
| Cost of additional uterotonics per woman (40 IU oxytocin and 800 µg misoprostol) (in naira) (%) | N/A | 1,860 | 480 | 2,340 |
PPH: Postpartum hemorrhage, C-section: Cesarean section, IU: International unit, N/A: Not applicable
Budget impact analysis
We modeled the gradual introduction and utilization of HSC over 5 years, from 0% in 2024 to a 17% utilization rate by 2028, as shown in Tables 3 and 4, to derive the yearly and cumulative budget impact.
| Intervention | 2024 | 2025 | 2026 | 2027 | 2028 |
|---|---|---|---|---|---|
| Heat-stable Carbetocin | N/A | N/A | N/A | N/A | N/A |
| Oxytocin (%) | 65.0 | 65.0 | 65.0 | 65.0 | 65.0 |
| Misoprostol (%) | 11.5 | 11.5 | 11.5 | 11.5 | 11.5 |
| Oxytocin±Misoprostol (%) | 23.5 | 23.5 | 23.5 | 23.5 | 23.5 |
N/A: Not applicable
| Intervention | 2024 (%) | 2025 (%) | 2026 (%) | 2027 (%) | 2028 (%) |
|---|---|---|---|---|---|
| Heat-stable Carbetocin | 1.5 | 4.0 | 8.0 | 13.0 | 17.0 |
| Oxytocin | 64.0 | 62.5 | 60.0 | 58.0 | 54.5 |
| Misoprostol | 11.0 | 10.5 | 10.0 | 9.0 | 9.0 |
| Oxytocin±Misoprostol | 23.5 | 23.0 | 22.0 | 20.0 | 19.5 |
Cost-effectiveness
We considered introducing HSC versus the other uterotonics for PPH prevention in the health system. To underscore the effects of the different inputs on results, we conducted scenario analysis by modifying different variables and comparing the cost-effectiveness of HSC to each of oxytocin, misoprostol, and oxytocin–misoprostol. A one-way sensitivity analysis (OWSA) was performed to assess the effect of changing input parameters on the results. The pair-wise sensitivity analysis (PSA) assessed the reliability of the study results, using oxytocin as the comparator to HSC at a willingness-topay threshold of Nigerian Naira (₦)3,233,297. The PSA ran through 5,000 iterations from the base case analysis.
RESULTS
Clinical Impact
Based on the total cohort of 2,548,136 women giving birth, the clinical impact analysis found that all PPH events, particularly severe PPH events and PPH deaths, will be significantly reduced with HSC introduction. There is a 39%, 50%, and 18% difference in all PPH events when HSC is administered prophylactically compared to oxytocin, misoprostol, and oxytocin–misoprostol combination, respectively, as shown in Table 5.
| Intervention (prophylactic) | Effectiveness of all PPH events | Incremental effectiveness of all PPH events | Percentage additional all PPH events (Comparator vs. HSC) (%) |
|---|---|---|---|
| HSC | 285,627 | ||
| Oxytocin | 397,279 | 111,652 | 39 |
| Misoprostol | 429,366 | 143,739 | 50 |
| Oxytocin± Misoprostol | 337,342 | 51,715 | 18 |
PPH: Postpartum hemorrhage, HSC: Heat-stablecarbetocin
This translates, as shown in Table 6, into a 15%, 38%, and 7% difference in severe PPH events and 21%, 41%, and 12% reduction in PPH deaths.
| Intervention (prophylactic) | Effectiveness of severe PPH events | Incremental effectiveness of severe PPH events | Percentage of additional severe PPH events (Comparator vs. HSC) (%) |
| HSC | 85,388 | ||
| Oxytocin | 98,261 | 12,873 | 15% |
| Misoprostol | 117,441 | 32,053 | 38% |
| Oxytocin±Misoprostol | 91,095 | 5,707 | 7% |
| Intervention (prophylactic) | Effectiveness death | Incremental effectiveness death | Percentage additional deaths (comparator vs. HSC) |
| HSC | 5,422 | ||
| Oxytocin | 6,587 | 1,165 | 21 |
| Misoprostol | 7,643 | 2,221 | 41 |
| Oxytocin±Misoprostol | 6,064 | 642 | 12 |
PPH: Postpartum hemorrhage, HSC: Heat-stablecarbetocin
Cost Impacts
Based on the same cohort, cost impact analysis shows a 6% lower cost attributed to HSC compared to oxytocin and oxytocin–misoprostol combination. However, despite a greater number of PPH cases averted, about a 3% higher cost is attributed to HSC compared to misoprostol [Table 7].
| Intervention (prophylactic) | Total costs (in Naira) | Incremental costs versus HSC (in Naira) | Percentage difference |
| HSC | 51,741, 431,419 | ||
| Oxytocin | 55,026,681,607 | +3,285,250,188 | +6.3 |
| Misoprostol | 50,366,650,788 | −1,374,780,631 | −2.7 |
| Oxytocin±Misoprostol | 54,794,993,036 | +3,053,561,618 | +5.9 |
| Intervention (prophylactic) | Costs/Woman (in Naira) | Incremental costs versus HSC | Percentage difference |
| HSC | ₦20,306 | ||
| Oxytocin | ₦21,595 | +₦1,289 | +6.3 |
| Misoprostol | ₦19,766 | −₦540 | −2.7 |
| Oxytocin±Misoprostol | ₦21,506 | + ₦1,200 | +5.9 |
PPH: Postpartum hemorrhage, HSC: Heat-stablecarbetocin, ₦: Naira (Nigerian)
Cost-Effectiveness
A comparison of HSC with each of the comparator uterotonics in this study found HSC to be dominant (more cost-effective) compared to oxytocin and oxytocin–misoprostol combination. However, when compared to misoprostol, the use of HSC came at a higher cost despite greater health benefits (number of PPH cases averted, DALYs averted, and deaths avoided) [Table 8].
| Intervention (prophylactic) | DALYs | DALYs Averted** | Deaths avoided** | Incremental costs (in NGN) per woman* | ICER DALYs averted |
|---|---|---|---|---|---|
| HSC | 145,013 | ||||
| Oxytocin | 176,455 | 0.012 | 0.00046 | −1,289 | HSC dominant |
| Misoprostol | 204,549 | 0.023 | 0.00087 | 540 | 23,092 |
| Oxytocin±Misoprostol | 162,085 | 0.007 | 0.00025 | −1,198 | HSC dominant |
Scenario Analyses
Results from changing key input assumptions in Table 9 show that, at base, HSC is dominant over oxytocin and oxytocin–misoprostol combination in terms of efficacy and cost. While in the case of misoprostol, it was more efficacious but less favorable cost-wise. Specifically, HSC outperformed oxytocin and oxytocin–misoprostol combination when the differential risk for anemia was excluded, input for the duration of the hospital stay is drawn from the CHAMPION trial, and when dosing for misoprostol is set at 400 mcg. In scenarios where cold-chain costs are excluded, when no higher-than-average dose of oxytocin is administered for prophylaxis to compensate for drug degradation, and where a discount is applied to the cost of oxytocin and misoprostol, oxytocin and oxytocin– misoprostol outperformed HSC.
| Intervention | ICER (DALYs) | NMB (N) |
|---|---|---|
| Base case | ||
| Oxytocin | HSC dominant | 41,185 |
| Misoprostol | 23,092 | 75,004 |
| Oxytocin±Misoprostol | HSC dominant | 22,861 |
| Exclude cold-chain costs | ||
| Oxytocin | 16,388 | 39,694 |
| Misoprostol | 27,602 | 74,898 |
| Oxytocin±Misoprostol | 37,979 | 21,408 |
| Source for efficacy: CHAMPION trial (vaginal births, additional uterotonics blood transfusions) | ||
| Oxytocin | 23,676 | 15,299 |
| Exclude differential risk for anemia. | ||
| Oxytocin | HSC dominant | 38,140 |
| Misoprostol | 28,188 | 70,734 |
| Oxytocin±Misoprostol | HSC dominant | 20,783 |
| No higher average dose of oxytocin for prophylaxis to compensate for the degradation of quality | ||
| Oxytocin | 5,752 | 39,825 |
| Misoprostol | 26,182 | 74,932 |
| Oxytocin±Misoprostol | 20,209 | 21,810 |
| Dosing for misoprostol prophylaxis: 400 mcg | ||
| Oxytocin | HSC dominant | 40,164 |
| Misoprostol | 31,289 | 74,812 |
| Oxytocin±Misoprostol | HSC dominant | 21,805 |
| The costing method applies a discount on the drug costs of oxytocin and misoprostol | ||
| Oxytocin | 155 | 39,894 |
| Misoprostol | 31,755 | 74,801 |
| Oxytocin±Misoprostol | 14,064 | 21,566 |
| Source of Duration of Hospital stay: CHAMPION | ||
| Oxytocin | HSC dominant | 40,011 |
| Misoprostol | 33,936 | 74,750 |
| Oxytocin±Misoprostol | HSC dominant | 21,810 |
PPH: Postpartum hemorrhage, HSC: Heat-stablecarbetocin, DALY: Disability-adjusted life year, ICER: Incremental cost-effectiveness ratio, NMB: Net monetary benefit
Sensitivity Analyses
From the OWSA, the most influential variables in order of importance are shown in Table 10. Parameters with the greatest impact on DALYs averted are predominantly related to cold-chain costs, administration of additional uterotonics, and the cost of hospital stay.
| Parameter name | Lower bound | Upper bound | Difference |
|---|---|---|---|
| Cold-chain costs: Transport, testing, and management | −819 | −1,496 | 677 |
| Oxytocin additional uterotonics required-vaginal births | −1,144 | −1,346 | 203 |
| Carbetocin additional uterotonics required-vaginal births | −1,354 | −1,263 | 91 |
| Duration of hospital stay after delivery (mild-to-moderate PPH)-SHC | −1,250 | −1,337 | 87 |
| Cold-chain costs: Percentage of vials disposed of | −1,230 | −1,311 | 81 |
| Cost of a 1-day hospital stay-SHC | −1,262 | −1,332 | 60 |
| Duration of hospital stay after delivery (no PPH)-SHC | −1,316 | −1,275 | 59 |
| Oxytocin additional uterotonics required-C-section | −1,264 | −1,298 | 34 |
| Proportion of C-section births | −1,262 | −1,291 | 28 |
| SHC-duration of hospital stay-mild-to-moderate PPH -C-section | −1,276 | −1,303 | 26 |
PPH: Postpartum hemorrhage, HSC: Heat-stablecarbetocin, OWSA: One-way sensitivity analysis, SHC: Secondary health care, C-section: Cesarean section
Results from the pairwise sensitivity analysis (PSA) found convergence across several parameters following 5000 iterations, as shown in Figure 3. There is a 99.8% probability that the results found in the base case are accurate (i.e., HSC has a lower incremental cost and higher DALYs averted compared to oxytocin). Tables 11 and 12 show that HSC is dominant when compared to oxytocin.
- Incremental cost-effectiveness scatter plot. PSA: Pair-wise sensitivity analysis, x-axis: Incremental effectiveness (DALYs averted), y-axis: Incremental changes in cost.
| Intervention | Total costs per woman (Naira) | DALYs | Incremental costs (Naira) | DALYs averted | ICER (Cost per DALYs averted) |
|---|---|---|---|---|---|
| Heat-stable Carbetocin | 21,595 | 0.069 | |||
| Oxytocin | 20,306 | 0.057 | −1,289 | 0.012 | HSC dominant |
DALY: Disability-adjusted life year, ICER: Incremental cost-effectiveness ratio
| Intervention | Total costs per woman (Naira) | DALYs | Incremental costs (Naira) | DALYs averted | ICER (Cost per DALYs averted) |
|---|---|---|---|---|---|
| Heat-stable Carbetocin | 21,570 | 0.068 | |||
| Oxytocin | 20,286 | 0.056 | −1,284 | 0.012 | HSC dominant |
DALY: Disability-adjusted life year, ICER: Incremental cost-effectiveness ratio, PSA: Pair-wise sensitivity analysis
Budget Impact
Introducing and scaling HSC from 0% to 17% market share of prophylactic uterotonic use over 5 years (2024–2028) was associated with a reduction in annual healthcare system expenditure on PPH care, driven by the reduction in overall PPH events, as shown in Tables 13 and 14. Specifically, these potential budgetary savings from 2024 to 2028, equal ₦352,798,943 (USD $ 238,186) (₦352,798,943) by 2028 and a total of NGN ₦691,917,648 (USD $466,881).
| 2024 | 2025 | 2026 | 2027 | 2028 | |
|---|---|---|---|---|---|
| Total PPH Cases (current scenario – excludes HSC) | 93,046 | 95,412 | 97,839 | 100,327 | 102,878 |
| Total PPH Cases (new scenario – includes HSC) | 92,574 | 94,304 | 95,770 | 97,223 | 98,591 |
| Clinical impact (Total PPH cases averted) | 473 | 1,108 | 2,069 | 3,104 | 4,287 |
| Cumulative PPH cases averted | 473 | 1,581 | 3,650 | 6,754 | 11,141 |
PPH: Postpartum hemorrhage, HSC: Heat-stablecarbetocin
| 2024 | 2025 | 2026 | 2027 | 2028 | |
|---|---|---|---|---|---|
| Total costs (current scenario) | 15,291,425,699 | 15,658,419,916 | 16,034,221,994 | 16,419,043,322 | 16,813,100,361 |
| Total costs (new scenario) | 15,283,901,043 | 15,632,060,851 | 15,971,855,252 | 16,313,833,924 | 16,661,761,281 |
| Budget impact (Savings) | 7,524,657 | 26,359,065 | 62,366,742 | 105,209,398 | 151,339,081 |
| Cumulative savings | 7,524,657 | 33,883,722 | 96,250,464 | 201,459,862 | 352,798,943 |
The current scenario excludes HSC; the New scenario includes HSC. HSC: Heat-stablecarbetocin
DISCUSSION
Nigeria continues to account for a significant number of maternal deaths globally. To address this, new initiatives like using HSC to prevent PPH, provision of bundled care for PPH treatment, promotion of local production of quality uterotonics, and training of healthcare workers for skilled birth attendance are being implemented. These efforts aim to significantly reduce PPH-related maternal mortality and morbidity.
Our study shows that using HSC as the main uterotonic for PPH prevention significantly reduces its incidence. This aligns with Matthijsse et al., who found a reduction of 3.42 in all PPH events.[23] Korb et al.[24] reported that introducing HSC for PPH prevention lowers costs per woman and overall health system expenses compared with oxytocin and oxytocin–misoprostol combination. However, despite greater health outcomes, HSC is more expensive compared to misoprostol. These cost savings in favor of HSC are highest when compared to oxytocin. Barrett et al. also noted that replacing oxytocin with HSC for PPH prevention could lead to annual savings in Canadian and Colombian healthcare systems for both low- and high-risk patients.[25,26]
Using a demand-side cost-effectiveness threshold, we found that HSC is more cost-effective and effective in preventing PPH than both oxytocin and the oxytocin–misoprostol combination. HSC offers better health outcomes at a lower cost to the health care system, similar to findings from Mexico.[27] Scenario analyses indicate that HSC consistently dominates oxytocin and oxytocin–misoprostol combination. However, it does not dominate misoprostol in most scenarios, except for one involving hospital stay duration based on CHAMPION data. In that scenario, while HSC had a higher total cost, it continued to reflect consistently favorable health outcomes compared to misoprostol.
Reducing the clinical burden of PPH benefits women, enhances society’s productivity, and lowers demand on the public health system. Cost-effectiveness analyses guide decision-makers in selecting interventions with higher health impact and cost benefits. HSC is suited to mitigate the current situation of sub-optimal uterotonic (oxytocin) efficacy due to fragile cold-chain infrastructure, poor electricity supply, and high heat and humidity.
HSC’s efficacy and heat-stable favorably impacts the Nigerian health system in a number of ways: (1) Aversion of PPH events; (2) cost-savings from reduced incidence of PPH events; (3) lowering the need for additional uterotonics; (4) consistency in uterotonic quality builds trust among providers and patients; and (5) promotes health equity by ensuring birthing women gain reliable access to a high-quality prophylactic uterotonic. Furthermore, our analysis suggests that as HSC scales, its health outcomes and cost savings increase, allowing for reinvestment in other important public health areas.
Limitations
The model considers solely direct costs to the healthcare system and does not consider indirect costs (e.g., healthcare provider training). It excludes non-pharmaceutical medical interventions such as uterine balloon tamponade, non-pneumatic antishock garment, and hysterectomy, which may result in an under-estimation of the total economic costs and health outcomes across all the interventions.
As found in other studies,[28] some data inputs had limitations due to the unavailability of data (e.g., hospital and cold-chain costs, time required by healthcare providers to manage PPH, amount of blood units needed for transfusion, and percentage of women receiving the oxytocin–misoprostol combination for prophylaxis), we therefore relied on subjective information from KOLs for these areas.
Ergometrine, as an alternative uterotonic for PPH prevention,[29] was excluded due to its limited use. Tranexamic acid alone or as part of the E-MOTIVE bundle to treat PPH[30] was also not included, suggesting an underestimation of the total cost estimates and health outcomes across all the interventions. Poor-quality misoprostol (e.g., additional dosing, wastage) was excluded, despite a 2020 WHO systematic review indicating nearly 40% failure rates for its use.[31]
CONCLUSION AND GLOBAL HEALTH IMPLICATIONS
The study outcomes provide key insights for decision-makers as they consider the most appropriate uterotonics to prevent PPH, reduce complications and costs related to PPH, and enhance financial management in healthcare. Improving PPH prevention and other complementary interventions will help attain SDG 3.1 and 3.8 for better maternal and newborn care outcomes.
The inclusion of HSC for PPH prevention in healthcare packages promotes health equity by ensuring high-quality products. It also reduces PPH-related health complications and maximizes the use of limited resources for greater public health benefits. Additionally, it addresses issues relating to evidence-based practice, quality of care, ethics, and universal health coverage principles.
Key Messages
(1) Heat-stable carbetocin is a highly cost-effective intervention for preventing postpartum hemorrhage compared to current standard of treatment. (2) Reduced cold-chain, and logistical costs and sustained efficacy at high temperature makes it particularly suitable for use in low-resource settings like Nigeria.
Acknowledgments:
(1) Dr. Oludemilade Effiong, Kehinde Muraina, Ledum Bwale, Isaac Erinfolami, Dr. Fatima Muhammad (Clinton Health Access Initiative). (2) John R. Cook (Economic Modeling, Complete HEOR Solutions, LLC, PA, USA) and Dr. Kunal Saxena (Center for Observational and Real-World Evidence, Merck and Co., Inc., NJ, USA) for their foundational work on the economic model structure. (3) Emily Crawford and Alana Garvin (Clinton Health Access Initiative) for their support on protocol development and creation of data collection tools, and data analysis.
COMPLIANCE WITH ETHICAL STANDARDS
Conflicts of Interest: The authors declare no competing interests; Financial Disclosure: Nothing to declare; Funding: The Smiles for Mothers program supports the Federal Ministry of Health in Nigeria and State governments of Kano, Lagos and Niger to reduce maternal deaths due to PPH through innovations in Service Delivery and Supply Chain Management. This analysis was supported by funding through MSD for Mothers, an initiative of Merck & Co., Inc., Rahway, NJ, U.S.A. The authors are solely responsible for the content of this manuscript. Ethics Approval: The study team adhered to the highest ethical standards and obtained all required federal and state-level scientific research ethics approvals for this study. All methods were carried out in accordance with relevant guidelines and regulations. Ethical approvals obtained for this study included from the National Health Research Ethics Committee of Nigeria (NHREC Approval number NHREC/01/01/2007-16/04/2021), Kano State Health Research Ethics Committee (Ref No: MOH/ off/797/T.I/2097), Lagos State Health Research Ethics Committee (Ref No: LREC/06/10/1499), Niger state Health Research Ethics Committee (Ref No: STA/495/vol/176) and Study participants provided informed consent after careful perusal of the consent form. All information about the participants and health facilities has been anonymized, and high protocol on confidentiality and safety has been maintained. Declaration of patient consent: Patient’s consent not required as there are no patients in this study. Use of artificial intelligence (AI)-assisted technology for manuscript preparation: The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript, and no images were manipulated using AI. Disclaimer: None.
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