Key challenges in pediatric vaccine trials in low- and middle- income countries

Low- and middle-income countries (LMICs) bear a disproportionate burden of infectious diseases, with 90 % of preventable cases occurring in these regions.[1] The presence of vaccine trials has not always reflected this impact. In 2005, North America and Europe hosted 94 % of all trials.[2] However, there has since been a redistribution of trial locations that aligns more closely with disease burden.

The path from recognizing the need for pediatric vaccine trials in LMICs to successfully implementing them comes with complex challenges.

Amplification of common pediatric vaccine challenges

Safety monitoring, crucial in all pediatric trials, requires additional care in LMICs where baseline health status and environmental factors may differ significantly from high-income countries (HICs). Researchers must be vigilant for potential adverse effects that might not be apparent in other populations.

The impact of immune system maturation on vaccine efficacy and safety is another common concern in pediatric trials.[3] In LMICs, this issue intersects with factors like malnutrition and higher infectious disease burden, potentially affecting immune responses in ways not seen in other settings.

Community engagement and cultural considerations

Effective community engagement is crucial for successful trials. In LMICs, researchers must address cultural norms, language barriers and varying levels of health literacy. Teams may face difficulties explaining complex medical concepts to parents with limited formal education, potentially in languages that lack specific scientific terminology.

Cultural nuances that influence decision-making processes further complicate these interactions. This may include a need to obtain consent from community elders, for example.

Infrastructure and resource limitations

Conducting a vaccine trial requires specialized equipment, such as reliable cold chains for vaccine storage and trained personnel to manage every aspect of the study. While recent years have seen improvements in LMICs, resources often taken for granted in high-income countries can be scarce or unreliable in LMIC settings.

In many LMICs, there may be a limited pool of individuals with the necessary training and experience. This often necessitates extensive capacity-building efforts as part of the trial preparation, which can impact timelines and budgets. However, these efforts also present an opportunity to leave a lasting positive impact on local healthcare systems beyond the scope of the individual trial.

Ethical complexities

Ethical considerations take on heightened importance in LMIC settings, particularly given historical instances of unethical research practices in some regions. Researchers must carefully balance scientific rigor with the utmost respect for participant rights and well-being.

One key ethical dilemma revolves around the choice of comparators in vaccine trials. Researchers must decide whether to compare a new vaccine to a placebo, potentially denying some participants protection against a prevalent disease, or test it against an existing vaccine that might not be readily available in the local healthcare system. These decisions require careful consideration of local health priorities, scientific validity and ethical standards.

Regulatory variability

Each country has its own set of regulations, which may differ significantly from international standards. This variability can affect everything from protocol approvals to data reporting requirements.

In some cases, regulatory bodies in LMICs may have limited experience with complex clinical trials, potentially leading to longer approval processes or inconsistent interpretations of guidelines. Researchers must be prepared to adapt their approaches while maintaining rigorous scientific standards.

Long-term impact and sustainability

The responsibilities of researchers extend beyond the conclusion of a trial. Ensuring that successful vaccines reach the communities that participated in their development is both an ethical obligation and a practical necessity for improving global health.

Moreover, there is a growing recognition of the need to build sustainable research capacity in LMICs. This involves not just conducting individual trials, but fostering local expertise, strengthening regulatory frameworks and supporting the development of manufacturing capabilities. The challenge lies in designing trials that contribute to these long-term goals while meeting immediate research objectives.

Charting a path forward

Innovative approaches to trial design, community engagement and capacity building offer promising avenues for conducting effective and ethical pediatric vaccine trials in LMICs. Additionally, there's a growing focus on leaving a lasting positive impact on local healthcare systems. By addressing these challenges directly, the scientific community is working toward a future where the benefits of vaccine research are more equitably distributed.

For a deeper exploration of solutions to these challenges and insights on designing effective, ethical pediatric vaccine studies in LMICs, download our white paper.

Références

[1]. Mardini A, Shaykhon N, Khan A, Mardini A, Saeed H. “Global disparities in access to vaccine clinical trials: a review of the literature.” Vaccines, 348, 12(4), 2024. https://doi.org/10,34/vaccines12040348

[2]. Grenham A, Villafana T. “Vaccine development and trials in low and lower-middle income countries: Key issues, advances, and future opportunities.” Human vaccines & immunotherapeutics, 2192-2199, 13(9), 2017. https://doi.org/10,11/21645515.2017.1356495

[3]. Cooper D, Afghani B, Byington C, et al. “SARS-CoV-2 vaccine testing and trials in the pediatric population: biologic, ethical, research, and implementation challenges.” Pediatric Research, 966-970, 90, 2021. https://doi.org/10,1/s41390-021-01402-z