Feasibility, Acceptability, and Appropriate Use of Novel and Lesser-Used Medicines for Prevention and Treatment of Postpartum Hemorrhage: Evidence from Implementation Research

INTRODUCTION

Despite progress, maternal mortality rates remain at unacceptably high levels, raising the alarm for not being able to reach the Sustainable Development Goal (SDG) 3 maternal mortality target by 2030.^[1] To accelerate progress, addressing the direct causes of maternal mortality and morbidity remains a priority, especially postpartum hemorrhage (PPH) which continues to be the leading direct cause of maternal death. The SDG 3.1 target is to achieve a global maternal mortality ratio (MMR) of less than 70 maternal deaths per 100,000 live births by 2030; however, the reduction in MMR has stagnated in most regions between 2016 and 2020.^[2] This necessitates an understanding of in-country realities, identifying key priorities for research, advocacy, and implementation and translating what good looks like into action.

PPH is defined as maternal blood loss of 500 ml or more after birth and results in approximately 70,000 maternal deaths annually.^[3] Consequently, immediate administration of uterotonics by healthcare providers post-delivery is crucial and to have emergency care available during and after birth if required. The urgency to address stagnant PPH figures and global efforts to increase the investment in essential medicines has allowed for evidence generation on the effectiveness of heat-stable carbetocin (HSC), a long-acting oxytocin analog, for PPH prevention,^[4,5] and tranexamic acid (TXA), an antifibrinolytic, for PPH treatment,^[6] with the added advantage of not requiring a cold chain to maintain quality. This is important in settings where the cold chain is at risk of being compromised. Nonetheless, barriers to accessing quality PPH care in low- and middle-income countries (LMICs) hinder these medicines’ potential to reduce maternal deaths, rendering their translation into health policies and clinical practice challenging. Important steps for achieving access include the revision and update of national policies surrounding key priority maternal and newborn health recommendations, and catalyzing political will to operationalize an accelerated pathway to access these interventions for populations with the greatest need. Policy change shortens the interval in getting World Health Organization (WHO) PPH recommendations adopted within countries, and implementation research studies facilitate strategies for national-level adaptation of recommendations into clinical practice.

PATHWAY TO PRODUCT INTRODUCTION AND ACCESS

Collaborative Efforts

A 2019–2022 collaboration between Concept Foundation, WACI Health, the International Federation of Gynecology and Obstetrics, and the International Confederation of Midwives (as well as key regional and national stakeholders) was aimed at accelerating access to HSC and TXA in 15 sub-Saharan African countries (see Table 1 for country status at project end). The project shed light on some of the key barriers associated with implementing new recommendations for PPH prevention and management. These include a disconnect between global recommendations and national adoption, time-consuming in-country processes to update policies and clinical protocols, and limited cross-talk between key sectors.^[7] Our learnings include the need for (1) a coordinated guideline development and dissemination strategy, (2) a supported health system to ensure the availability of these essential medicines, (3) comprehensive training of skilled healthcare providers according to evidence-based recommendations, (4) intersectoral collaboration and harmonization, and (5) evidence generation on the feasibility, acceptability, and appropriate use to support the successful implementation of the updated guidelines.

Table 1: Status of inclusion of heat-stable carbetocin and tranexamic acid into national guidelines and EMLs

Country*	National guideline status	National EML status
1. Burkina Faso
2. DRC
3. Ethiopia
4. Ghana
5. Liberia
6. Rwanda
7. Senegal
8. South Sudan
9. Sierra Leone
10. Ivory Coast
11. Uganda

* Burundi, Mali, Tanzania, and Zanzibar did not progress in revising their national guideline and EML within the time frame due to a range of contextual factors, including the recent update of national policies. EML: Essential Medicines List

RECOMMENDATIONS BASED ON STUDIES’ FINDINGS

Our recommendations based on the collective evidence generated in this Special Collection are to foster an enabling environment for the scale-up of HSC and TXA as new and lesser-used commodities. First, investment in health system strengthening demands multi-sectoral, concerted efforts for capacity building, centralized procurement, and improving the supply chain. This includes (but is not limited to) stakeholders such as policymakers, donors, procurement agencies, professional associations, non-governmental organizations, and civil society organizations. Second, healthcare providers are necessary to building resilient health systems, and empowering midwives, given their vital frontline contributions, should be incorporated into PPH training and supportive supervision. Third, a paradigm shift, on the perceived low return on investment in maternal health medicines, is needed to address structural maternal health market barriers and align with global efforts to reduce maternal mortality. There can be limited awareness and/or acceptance of this bottleneck at the ministry level as well as limited knowledge of new maternal and newborn health interventions that are particularly suited to LMIC realities. We believe targeted, multi-level demand generation can greatly amplify advocacy activities for policy change and beyond.

CONCLUSION AND GLOBAL HEALTH IMPLICATIONS

Lessons learned from all studies in this Special Collection include the need for a holistic and streamlined approach to PPH training that adheres to evidence-informed practices, engaging key stakeholders, and improving health information systems to support an enabling environment for the safe introduction of essential maternal health interventions into clinical practice. Additionally, there is a pressing need to enhance the data recording quality and ensure that key data is consistently captured in routine health records. This limitation can be addressed through regular supportive supervision and continuous monitoring and evaluation in the implementation of HSC and TXA to ensure ongoing effectiveness and safety. A larger sample size across all studies would also help improve the generalizability of the results.

Overall, the studies collectively indicate that the safe introduction and use of HSC and TXA in primary, secondary, and tertiary facilities is feasible and favorable to healthcare providers. Our goal is that this Special Collection underscores the safety, feasibility, and acceptability of introducing quality-assured HSC and TXA and also the importance of appropriate training and implementation research to meaningfully advance the field by building the evidence base for scale-up across various LMIC contexts. The global health implications are defining steps needed to introduce essential PPH medicines safely and effectively into the public health system of LMICs and the importance of implementation research to support safe and appropriate introduction into clinical practice. The potential impact is generating evidence to inform future national policy decisions that enhance PPH quality of care, ultimately improving maternal health outcomes and advancing the SDGs.