Methodological challenges in measuring vaccine effectiveness using population cohorts in low resource settings

Area of Science:

• Epidemiology
• Public Health
• Vaccinology

Background:

• Post-licensure vaccine effectiveness (VE) studies are crucial for assessing real-world impact, including indirect effects.
• Large cohort studies are vital for VE evaluation but present methodological challenges, especially in developing countries.
• Routine vital surveillance is often lacking in low-resource settings, necessitating robust epidemiological approaches.

Purpose of the Study:

• To evaluate the post-introduction effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13) against all-cause infant mortality.
• To assess the effectiveness of monovalent rotavirus vaccine (RV1) against diarrhea-related infant mortality.
• To conduct a methodological review of cohort studies for VE in a developing country context.

Main Methods:

• An open prospective cohort study was conducted in two rural Malawian sites (population 500,000).
• Methodological review focused on defining denominator (study population), exposure (vaccination status), and outcome ascertainment (mortality).
• Sensitivity analyses were proposed to address potential biases and interrogate methodological decisions.

Main Results:

• The study evaluated PCV13 and RV1 effectiveness using a large-scale cohort in Malawi.
• Methodological considerations for defining study parameters were assessed for their impact on power, effect size, and bias.
• The study illustrates the application of these definitions within the Malawian cohort context.

Conclusions:

• Large-scale real-world cohort studies can provide robust evidence on vaccine benefits in reducing child mortality, even with limited surveillance.
• Acknowledging the balance between definitions and their impact on estimated VE is crucial for policy decisions.
• Such studies offer compelling evidence for policymakers regarding the total benefits of newly introduced vaccines.