The primary aim of NirseCL is to evaluate the effectiveness of nirsevimab against
Respiratory Syncytial Virus (RSV) in infants during the 2024 RSV season in Chile. The
secondary objective is to determine the impact on RSV-related health outcomes at a
national level.
The target population to receive nirsevimab is approximately 160,000 subjects, including
the entire newborn cohort born during the autumn-winter season, from April 1st, 2024, to
September 31st, 2024, infants born from October 1st, 2023, to March 31st, 2024, which are
6 to 1 month old at the time of immunization in April-June, and the high-risk group
defined as infants born with 29 weeks of gestational age (wga) or less who were born
within nine months of the beginning of the RSV season; those born with Bronchopulmonary
Dysplasia (BPD), 32 or less wga and/or a birth weight less than 1·5 kgs born within one
year of the beginning of the RSV season, and newborns 34 or less wga and/or weight less
than 2·5 kgs born during the RSV season.
Nirsevimab will be administered as part of Chile's national immunization program,
following the implementation plan designed by the Ministry of Health. The coverage with
nirsevimab in the target population is expected to be high (95% for those born during the
winter campaign and 80% for those born before the beginning of the autumn-winter season).
The primary outcome measure for effectiveness will be lower-tract respiratory infection
hospitalizations (LRTI) attributed to RSV in the pediatric intensive care units (PICU) at
a nationwide and regional level, and the secondary outcomes will be overall LRTI
hospitalizations attributed to RSV, LRTI hospitalizations, and hospitalizations due to
any cause. Additional outcomes might be included if enough statistical power is attained.
Effectiveness will be determined using a two-step process. First, historical data will be
used to determine the set of ICD10 diagnosis codes that are attributable to RSV infection
by using data from the Chilean national sentinel program and consolidated hospitalization
records. Afterward, A series of complementary statistical analyses at different
aggregation levels will be conducted to estimate the impact of nirsevimab on the target
population. Detailed patient-level information will be used to compare LRTI
hospitalizations of those receiving the immunization against those who did not, using an
adjusted proportional hazard rates regression model to estimate the effectiveness of
nirsevimab as a function of covariates such as wga, weight at birth, sex, nationality,
maternal education, coexisting conditions, MMR vaccination (as an indicator of access to
medical care), and place of birth. This method has been used to evaluate recent
nationwide vaccination campaigns in Chile (Jara et al, 2021). A case-control matching
approach will be used as an alternative method intended to gain statistical efficiency
(Rose and van der Laan, 2009). Finally, as a robustness analysis, a synthetic control
method that allows the comparison of whole time series without relying on
individual-level data will be used (Bruhn et al., 2016).