Establishing a Multicenter Active Adverse Events Following Immunization Sentinel Surveillance Network Across 22 Tertiary Care Hospitals in India: Protocol for a Prospective Observational Study.

Background: The rapid evolution of immunization programs in low- and middle-income countries (LMICs) has necessitated an augmentation of capacity for postlicensure vaccine safety monitoring.

Objective: This study describes the protocol for establishing a Multicenter Active Adverse Events Following Immunization Surveillance System (MAASS) network in India, which conducted prospective observational surveillance for 12 adverse pediatric outcomes between November 1, 2017, and March 20, 2020.

Methods: A multistage site selection process was implemented, beginning with an initial screening survey followed by in-person visits to assess the suitability of potential tertiary care hospitals for inclusion in the network. We adopted a decentralized, collaborative approach to develop the study protocol, standardize case definitions, establish data collection procedures, and create a common data model for monitoring and analysis. Outcomes selected for surveillance included acute disseminated encephalomyelitis, anaphylaxis, aseptic meningitis, dengue, Guillain-Barré syndrome, Kawasaki disease, malaria, seizure, sepsis, thrombocytopenia, intussusception, and urinary tract infections. We screened all children aged 1-24 months who were hospitalized for more than 24 hours at participating sites to identify suspected or confirmed cases of these outcomes using a structured checklist. Written informed consent was obtained from the parent or legally authorized representative for inclusion in the study. Demographic, socioeconomic, and vaccine exposure information was collected for all included participants. Additional clinical information was gathered to assess the level of diagnostic certainty according to standardized case definitions. The study progressed through 3 distinct phases: network establishment (January-November 2017), active surveillance (November 2017-March 2020), and database analysis (April 2020-March 2024). The dissemination process is currently underway.

Results: A geographically representative data network was established across 15 public and 7 private tertiary care hospitals in 17 states and 1 union territory in India. During the study period, we screened 90,147 age-eligible admissions and confirmed 8362 cases with study outcomes. Using multiple analytic study designs, we generated a database of outcomes and exposures to investigate associations between vaccine-event pairs of interest.

Conclusions: The MAASS network is unprecedented in its scope and scale among LMICs. While the study is specific to India, the lessons learned in establishing and implementing the network offer valuable insights for developing active surveillance systems and strengthening capacity for benefit-risk evaluations of vaccines in resource-constrained settings.

International Registered Report Identifier (irrid): RR1-10.2196/64050.