Introduction of Heat-Stable Carbetocin through a Public-Private Partnership Model in India: A Retrospective Study to Determine Feasibility and Its Optimal Use in Public Health Settings

Background of the Study

Childbirth is the most crucial time when pregnant women and newborn babies are at the highest risk of morbidity and mortality. Nearly 46% of all maternal deaths and 40% of neonatal deaths usually occur during labor or the first 24 hours after birth. Postpartum hemorrhage (PPH), hypertension, sepsis, and obstructed labor are the major causes of maternal deaths.^[1] Most of these deaths can be prevented by conducting evidence-based practices during the period around childbirth.

The PPH is a leading cause of maternal death globally, accounting for about one-quarter of all maternal deaths. India, with its high maternal mortality rate (97 deaths per 10,000 live births from 2018 to 2020)^[2] is no exception, as 38% of maternal deaths are due to PPH.^[3]

Oxytocin, a World Health Organization (WHO) recommended uterotonic drug is one of the most widely used drugs for preventing and managing PPH. Oxytocin has a short half-life of 1–6 minutes,^[4] making it a suitable drug for safely inducing or augmenting labor in specific clinical scenarios.^[5] However, oxytocin is not without its challenges. Oxytocin is heat-sensitive and must be stored at 2–8 degrees Celsius,^[4] which is difficult to maintain in many low- and middle-income countries (LMICs) like India because of their insufficient cold chain capacity. As a result, studies have shown that much of the oxytocin available in LMIC markets like India either does not meet drug quality standards or is stored improperly.^[6–8]

In response to global interest in developing a heat-stable alternative to oxytocin for preventing PPH, a new drug, Heat-Stable Carbetocin (HSC), has been shown to prevent PPH effectively.^[9–11] Unlike oxytocin, HSC is stable at 30 degrees Celsius, which is advantageous in areas without adequate cold chain capacity.^[9] This drug is new to the market and has been registered recently in India, and injectable HSC (100 μg/mL) was added to the WHO’s Model List of Essential Medicines in 2021.^[12] At the same time, WHO has recommended HSC in contexts where the quality of oxytocin cannot be guaranteed.^[4] HSC is contraindicated for inducing and augmenting labor due to its long half-life of 40 minutes.^[4,5] Oxytocin and HSC pose unique challenges, particularly in India, where misuse of oxytocin is rampant and there is a risk of inappropriate HSC use.^[13]

A recent study from India showed that HSC prevents more disability-adjusted life years (DALYs) and reduces costs to the public healthcare system of India.^[14] In 2020, the Drug Controller General of India (DGCI) approved the use of HSC for preventing PPH, in alignment with WHO recommendations. However, no studies have been conducted so far to test the feasibility and optimal use of HSC in the existing public health system. Further research is imperative to ensure the safe and appropriate utilization of HSC to guide policymakers before its widespread adoption as an alternative to oxytocin for PPH prevention, particularly in settings where oxytocin quality may be questionable.

Under the leadership of the National Health Mission (NHM) of the State of Madhya Pradesh (MP) in India, a public-private partnership (PPP) was forged through the United States Agency for International Development’s (USAID) India-awarded Systems Approach for Maternal, Newborn, and Child Health (MNCH) focusing on Vulnerable Geographies (SAMVEG) project. A consortium partnership was formed, including IPE Global Limited, DIMAGI, Inc., World Health Partners, and John Snow India Private Limited, to demonstrate an innovative model using HSC as an entry point for strengthening active management of the third stage of labor (AMTSL). Ferring Pharmaceutical, the manufacturer of HSC, was also engaged in selected health facilities for its commitment to supply HSC. The key steps involved in the development and implementation of HSC model is presented as Figure 1.

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Figure 1:

Key steps involved in the development and implementation of the Heat-stable carbetocin (HSC) model.

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Study Objectives

The objectives of the study were to (1) understand the feasibility of introducing HSC through an innovative PPP model in the First Referral Unit (FRU) and non-FRU-level public health facilities; (2) understand the clinical practices for prophylactic use of HSC; and (3) understand the factors that enable the appropriate use of uterotonics in public health settings.

Specific Aim

The study aimed to assess the acceptability and feasibility of introducing the HSC through a PPP model, ascertain its appropriate use, and derive learnings for its possible scale-up across similar settings. Additionally, the study also aimed to examine the key factors that facilitate or restrict the appropriate utilization of HSC in public health systems, as per WHO recommendations.

Study Design and Settings

This was a retrospective study wherein we analyzed facility-level data collected between August 2022 and July 2023 from the 15 selected health facilities in the Dewas district of MP, where HSC was introduced through a PPP model. The health facilities comprised two FRU-level facilities, that is, one district hospital and one community health center (CHC), along with 13 non-FRU facilities: three CHCs, eight Primary Health Centers (PHCs), and two Health and Wellness Centers (HWCs).

Data Collection

At the facility level, usually a standardized paper-based delivery register and a case sheet are used for each delivery. Based on the findings of the situational analysis, new fields in the case sheet and delivery register were added to record the timing of uterotonic administration (within one minute of delivery). To ensure data accuracy, all service providers received training on AMTSL and the appropriate use of HSC as well as recording and reporting procedures before initiating the intervention. HSC was provided monthly using the state drug distribution system, and existing recording formats were adapted to include the uterotonic administration time. A nurse mentor provided supportive supervision and collected information related to the model once every month from each of the 15 facilities.

At the end of each month, facility staff gathers facility-level data from a paper-based delivery register. This data is then compiled using Microsoft Excel (Office 365) before being shared with the district nodal person based at the NHM for district-level compilation and analysis.

The monthly facility-wise delivery data compiled between August 2022 and July 2023 from all 15 health facilities were used to perform the analysis in this study.

Study Variables

The key outcomes of interest included: (1) the number of deliveries conducted in the facilities, deliveries where HSC was used, (2) the number of cases of HSC administration within one minute of delivery, (3) cesarean section deliveries that received HSC, and (4) patients given uterotonics for PPH management disaggregated by drug type. No personal identifiers of the beneficiaries delivered to health facilities were collected. Complete data analysis and interpretation were done in an aggregated form.

Statistical Analysis

We performed health facility-level analysis using Microsoft Excel (Office 365), and the results are reported in aggregated form in terms of frequencies and proportions. Additionally, the association between HSC use for PPH prevention and level of health facility was calculated and compared for statistical significance using Pearson’s chi-square test.

Ethical Approval

We received administrative authorization from the NHM of Madhya Pradesh before conducting this analysis. Additionally, this study was reviewed and approved by the International Institute of Health Management Research (IIHMR), New Delhi.

Main Variable Results

A total of 88 service providers, including 70 nursing officers, were trained by leveraging the state government’s logistics and trainers. Implementation one year after the model’s launch by the State Government and supply of HSC revealed that, as per the records of the delivery point, a total of 18,497 women were admitted for care at childbirth in the 15 implementing facilities. In addition, 543 pregnant women (2.9%) who had transit deliveries before they could reach the delivery points were also managed. However, these were not included in the analysis.

Uterotonic administration within one minute of delivery was almost universal (98.8%). No instance was recorded of using HSC either for induction of labor or management of PPH. Facility-wise uterotonic administration and mode of delivery are shown in Table 1.

In 636 cases (3.43%), HSC was not given for PPH prevention. PPH incidence documented in this study was 0.7%, with 126 reported PPH cases. A higher incidence was reported from non-FRU facilities (1.4%), and no PPH was reported in cesarean births. Uterine atony (69%) was the most reported cause of PPH, followed by birth trauma (23.8%). No case was reported where a surgical intervention was undertaken. At the same time, overall compliance with evidence-based monitoring practices with partograph (95.3%) and early initiation of breastfeeding (90.6%) was seen. The referral rate in PPH cases was 16.7%, and no death was reported, as shown in Table 2.

The Person’s chi-square test was employed to assess the association between the use of HSC for PPH prevention and the type of health facility. The results indicate a significant association, with notably higher utilization of HSC for preventing PPH observed in FRU-level facilities compared to non-FRU facilities (p < 0.001). Additionally, the administration of HSC within one minute of delivery was also significantly more frequent in FRU facilities compared to non-FRU facilities (p < 0.001) [Table 3]. A total of 12 structured district-level review meetings (one per month) were conducted by the district authorities to oversee the consistent availability of the HSC drug and address any challenges, including adverse drug events, encountered during the implementation of the HSC model. Based on implementation learnings, the district authorities decided to scale-up the model in all 32 delivery points of Dewas district. Presently, discussions are ongoing for incorporation of the HSC model into the state program implementation plans, paving the way for a statewide scale-up.

Strengths and Limitations of the Study

The main strength is that to the best of our knowledge, this is the first study from India on the use of HSC, which determined the feasibility and assessed the optimal use of HSC in the existing public health system. The results of this study can be used for policy decision-making and program purposes for using HSC as an alternative to oxytocin for the prevention of PPH in settings where oxytocin is of suspect quality.

Limitations of our study include data analysis on deliveries carried out at intervention facilities captured during the study time frame. We did not include women who gave birth while in transit (i.e., on their way) in the analysis due to insufficient documentation regarding the administration of uterotonics in such deliveries. Additionally, we did not collect additional data to ascertain the underlying reasons for relatively lower HSC utilization in non-FRU facilities. The potential factors might involve a higher incidence of contraindicated cases in non-FRU settings or issues related to knowledge, skills, fear, and apprehension among staff regarding the use of this newer drug for PPH prevention. Further research is necessary to delve into these reasons; however, such an investigation was beyond the scope of the current study.

Key Messages

• Our study demonstrated the feasibility of introducing Heat-Stable Carbetocin (HSC) and its appropriate use for postpartum hemorrhage (PPH) prevention in the existing health system of Madhya Pradesh, India.

• HSC is an alternative to oxytocin for preventing PPH in settings where oxytocin quality cannot be guaranteed. Capacity building of healthcare providers during Active Management of the Third Stage of Labor (AMTSL) will increase the effectiveness of care.

• Health system adaptations are necessary to ensure the optimization of HSC utilization and sustainable scale-up.