Lessons learnt from enrolment and follow up of pregnant women and their infants in clinical trials in South Africa, a low-middle income country

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Study Justification:
– Infectious causes are a significant contributor to morbidity and mortality in neonates and young infants.
– Immunization of pregnant women has shown benefits in protecting both the mother and her infant.
– Reluctance to include pregnant women in clinical trials is reducing, but still considerable.
– Low-middle income countries (LMIC) have the highest infectious disease burden and need interventions to reduce morbidity and mortality in mothers and infants.
– However, there is a lack of reliable background data on adverse pregnancy outcomes and limited experience in clinical trials in LMIC.
Highlights:
– Accurate gestational age assessment is challenging in LMIC due to limited access to early ultrasound examinations and unreliable assessment methods.
– Concomitant administration of recommended vaccines has been avoided in clinical trials, but this limitation could impact the interventions available to participants during antenatal care.
– Women in LMIC have a higher burden of concomitant illnesses and adverse pregnancy outcomes compared to higher income countries.
– Availability of local data is essential for safety monitoring committees to identify vaccine-related adverse events.
Recommendations:
– Include pregnant women in clinical trials in high-risk settings to reduce disease burden in them and their infants.
– Improve access to accurate gestational age assessment methods in LMIC.
– Consider allowing concomitant administration of recommended vaccines in clinical trials to provide participants with potentially beneficial interventions.
– Collect and document local data on adverse pregnancy outcomes and community opinions on immunization during pregnancy.
Key Role Players:
– Researchers and scientists conducting the clinical trials.
– Healthcare providers and clinicians involved in antenatal care.
– Regulators and policymakers responsible for approving and overseeing clinical trials.
– Safety monitoring committees to monitor vaccine-related adverse events.
– Community members and opinion leaders to provide input on immunization during pregnancy.
Cost Items for Planning Recommendations:
– Funding for research and clinical trial implementation.
– Training and capacity building for healthcare providers and researchers.
– Equipment and resources for accurate gestational age assessment.
– Data collection and analysis.
– Community engagement and education initiatives.
– Safety monitoring and adverse event reporting systems.

The strength of evidence for this abstract is 7 out of 10.
The evidence in the abstract is moderately strong. The abstract provides insights into the challenges and lessons learned from conducting clinical trials in pregnant women in South Africa. It highlights the difficulties in accurate gestational age assessment, the impact of concomitant illnesses on trial outcomes, and the importance of local data for safety monitoring. However, the abstract does not provide specific data or results from the clinical trials, which would strengthen the evidence. To improve the evidence, the abstract could include more details on the methodology, sample size, and specific outcomes of the trials.

Introduction: Infectious causes are a significant contributor to morbidity and mortality in neonates and young infants. Immunization of pregnant women to protect the mother and/or her infant is gaining momentum due to the benefits of this strategy demonstrated in numerous implemented strategies (Maternal and Neonatal Tetanus Elimination Initiative) and clinical trials.Reluctance by regulators, participants and healthcare providers to include pregnant women in clinical trials is considerable, but reducing. Infectious disease burden, and therefore need for interventions to reduce morbidity and mortality in mothers and infants, is highest in low-middle income countries (LMIC), however, reliable background data on adverse pregnancy outcomes and lack of experience in clinical trials and community opinions on immunization during pregnancy are not well documented. Methods: We used our experiences in conducting two clinical studies in pregnant women in South Africa to illustrate the challenges experienced and lessons learnt which may benefit others working in the maternal immunization field. Results: Accurate gestational age assessment, which is essential for clinical trials, is challenging in LMIC due to limited access to early ultrasound examinations, and unreliable assessment by history (last menstrual period date) and physical examination (symphyseal-fundal height).Concomitant administration of recommended vaccines has previously been avoided in clinical trials; however, this limitation could impact the potentially beneficial interventions that participants can access during antenatal care.Women in LMIC have a higher burden of concomitant illnesses (e.g. HIV infection, malaria and anaemia) and adverse pregnancy outcomes (e.g. stillbirth) than pregnant women in higher income countries. Availability of local data is essential for safety monitoring committees to identify vaccine-related adverse event triggers. Conclusion: Immunization of pregnant women to reduce disease burden in them and their infants is promising, and women in high-risk settings should be included in trials (Clinical trial registry number: ‘Study A’: NCT01193920, ‘Study B’: NCT01888471).

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Based on the provided description, here are some potential innovations that can be used to improve access to maternal health:

1. Mobile clinics: Implementing mobile clinics equipped with ultrasound machines and trained healthcare professionals can help improve access to accurate gestational age assessment in low-middle income countries (LMIC) where access to early ultrasound examinations is limited.

2. Integrated antenatal care: Introducing integrated antenatal care services that include the administration of recommended vaccines alongside routine antenatal care can ensure that pregnant women in LMIC have access to both essential vaccinations and regular check-ups.

3. Data collection and analysis: Establishing robust systems for collecting and analyzing local data on adverse pregnancy outcomes and vaccine-related adverse events can provide valuable information for safety monitoring committees and help identify potential triggers.

4. Community engagement: Engaging with local communities to understand their opinions and concerns regarding immunization during pregnancy can help address any reluctance or misconceptions and promote acceptance of maternal immunization strategies.

5. Capacity building: Investing in training programs and capacity building initiatives for healthcare providers in LMIC can enhance their knowledge and skills in conducting clinical trials involving pregnant women, thereby reducing reluctance and improving participation rates.

6. Collaboration and knowledge sharing: Encouraging collaboration and knowledge sharing among researchers, healthcare providers, and regulators across different countries and regions can facilitate the exchange of experiences, lessons learned, and best practices in the field of maternal immunization.

These innovations can help address the challenges and lessons learned from conducting clinical trials in pregnant women in South Africa and contribute to improving access to maternal health in LMIC.
AI Innovations Description
Based on the provided description, the following recommendation can be developed into an innovation to improve access to maternal health:

Title: Mobile Application for Maternal Health Monitoring and Immunization

Description: Developing a mobile application specifically designed for maternal health monitoring and immunization in low-middle income countries (LMIC) can significantly improve access to maternal health services. The application can address the challenges mentioned in the study, such as accurate gestational age assessment, concomitant administration of recommended vaccines, and availability of local data for safety monitoring.

The mobile application can have the following features:

1. Gestational Age Calculator: The application can include a tool to accurately calculate gestational age based on the last menstrual period date and physical examination. This can help healthcare providers in LMIC who have limited access to early ultrasound examinations.

2. Immunization Tracker: The application can provide a comprehensive immunization schedule for pregnant women, including recommended vaccines and their timing. It can send reminders to women for upcoming immunizations and track their immunization history.

3. Concomitant Illness Management: The application can provide information and resources on managing concomitant illnesses such as HIV infection, malaria, and anemia during pregnancy. It can offer guidance on appropriate interventions and connect women to healthcare providers for further support.

4. Safety Monitoring and Reporting: The application can allow healthcare providers to report and monitor vaccine-related adverse events in real-time. This data can be collected and analyzed to ensure the safety of immunizations during pregnancy.

5. Community Engagement: The application can include a community forum where pregnant women and healthcare providers can share experiences, ask questions, and provide support to each other. This can help address community opinions on immunization during pregnancy and create a supportive network.

By developing a mobile application specifically tailored to the needs of pregnant women in LMIC, access to maternal health services can be improved. The application can provide accurate information, support, and monitoring, ultimately leading to better maternal and infant health outcomes.
AI Innovations Methodology
In order to improve access to maternal health, here are some potential recommendations:

1. Mobile health (mHealth) interventions: Utilize mobile technology to provide information, reminders, and support to pregnant women, especially in low-resource settings where access to healthcare facilities may be limited.

2. Telemedicine services: Implement telemedicine platforms to enable remote consultations and monitoring for pregnant women, allowing them to receive medical advice and care without the need for physical visits to healthcare facilities.

3. Community health workers: Train and deploy community health workers to provide maternal health education, antenatal care, and postnatal support in underserved areas, bridging the gap between communities and healthcare facilities.

4. Transportation support: Establish transportation systems or programs to ensure pregnant women have access to timely and affordable transportation to healthcare facilities for antenatal care, delivery, and postnatal care.

5. Financial incentives: Provide financial incentives or subsidies to pregnant women to encourage them to seek and continue receiving maternal healthcare services, addressing financial barriers that may hinder access.

To simulate the impact of these recommendations on improving access to maternal health, a methodology could include the following steps:

1. Define the target population: Identify the specific group of pregnant women who would benefit from the recommendations, considering factors such as geographical location, socioeconomic status, and healthcare infrastructure.

2. Collect baseline data: Gather data on the current state of access to maternal health services in the target population, including metrics such as antenatal care attendance rates, facility delivery rates, and maternal health outcomes.

3. Model the interventions: Develop a simulation model that incorporates the recommended interventions, taking into account factors such as population size, intervention coverage, and potential impact on access to maternal health services.

4. Simulate the impact: Run the simulation model using the baseline data and the parameters of the interventions to estimate the potential impact on access to maternal health services. This could include metrics such as increased antenatal care attendance, improved facility delivery rates, and reduced maternal health complications.

5. Validate the simulation: Compare the simulation results with real-world data, if available, to assess the accuracy and reliability of the simulation model.

6. Refine and iterate: Based on the simulation results and validation, refine the model and repeat the simulation to explore different scenarios and variations of the interventions, optimizing the potential impact on improving access to maternal health.

By using this methodology, policymakers and healthcare providers can gain insights into the potential effectiveness of the recommended innovations and make informed decisions on implementing strategies to improve access to maternal health.

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