(347) Methodological considerations for the design and implementation of real-world vaccine-related studies in low- and middle-income countries

Background: Studies of infectious disease incidence/prevalence and real-world vaccine effectiveness and safety (RWVES) in low- and middle-income countries (LMIC) require specific considerations.

Objectives: To review recent real-world vaccine-related studies in LMIC to synthesize key lessons learned.

Methods: We reviewed 5 of our recent studies (past 3 years) in LMIC related to disease epidemiology and RWVES. Key design considerations and learnings from implementation were summarized.

Results: Source populations/geographies and healthcare delivery evaluation are key to identify appropriate locations/facilities for participant recruitment in each country. In incidence/prevalence studies, selected sites should have a clear catchment area and a patient population that is representative of disease epidemiology. This may require involvement of research-naive hospitals and/or non-hospital community facilities. In vaccine cohort studies, subjects need to be recruited at vaccination sites, which may not be healthcare facilities (e.g. schools), and unvaccinated controls need to be recruited from the same community.
In case of low literacy levels, culturally appropriate strategies to obtain consent/assent and tailored site training are needed. Pediatric studies should account for the recruitment setting (e.g. schools) to ensure one or both parents can be present to consent.
Access to existing data (e.g. national, regional, or local surveillance programs; individual medical records; vaccine registries) may be variable. Therefore, collection of key data, e.g. history of infectious disease and vaccination, is subject to recall bias and may require assessment of disease- or vaccination-related biomarkers. When follow-up data are needed, options for remote subject contact should account for accessibility to the internet and electronic devices (e.g. smartphones). Alternative solutions ranging from phone contacts to study staff visiting the communities can be envisioned.
Vaccine-related studies often require biological samples to assess prior vaccine and/or infectious disease exposure, or disease confirmation. Blood sampling strategies should consider cultural beliefs and acceptability, whilst ensuring consent/assent prior to sampling. They should also minimize participant burden (e.g. be community-based) and ensure robust technical sample handling, accounting for unpredictable seasonal weather and travel conditions.

Conclusions: Real-world vaccine-related studies in LMIC should consider variability in healthcare provision, and cultural and societal norms that could affect participant recruitment, retention and/or data collection and impact the interpretation of study results.