# LAIV trial 2015

## Description

This dataset is the complete data for the two-year LAIV efficacy trial conducted by AIIMS ND-CDC team at Ballabgarh, Dist Faridabad, Haryana. It has three sets of files - first one baseline demographic characteristic of study children and other two being surveillance dataset for each of the two years.

## Files

## Steps to reproduce

In June 2015, children were randomly allocated to LAIV, IIV, intranasal placebo, or inactivated polio vaccine (IPV) in a 2:2:1:1 ratio. In June 2016, vaccination was repeated per original allocation. Overall, 3041 children received LAIV (n=1015), IIV (n=1010), nasal placebo (n=507), or IPV (n=509). Mean age of children was 6·5 years with 20% aged 9-10 years. Through weekly home visits, nasal and throat swabs were collected from children with FARI and tested for influenza virus by polymerase chain reaction. The primary outcome was laboratory-confirmed influenza-associated FARI; vaccine efficacy (VE) was calculated using modified intention-to-treat analysis by Cox-proportional hazard model for each year. The study had three co-primary objectives: 1) to evaluate the relative efficacy of LAIV versus IIV and to evaluate the absolute efficacy of both 2) LAIV and 3) IIV versus a control vaccine to reduce the rate of laboratory-confirmed influenza virus infection among children with FARI aged 2-10 years in rural India. To estimate relative efficacy, the required sample size was 1000 children each in the LAIV and IIV groups assuming 50% VE for IIV and 75% for LAIV [21], influenza virus attack rate of 10%, 80% power, alpha of 0·05, and 10% attrition. To estimate absolute efficacy of LAIV and IIV, controls were combined to include 500 children each from the IPV and intranasal placebo groups. We followed a modified intention-to-treat (mITT) analytic plan, defined a priori to include children per their original allocated arm, with censoring of children lost to follow-up. Tables were finalized using dummy allocation of subjects for both years of data before un-blinding the allocation codes at the end of the second year. VE was calculated as (1- Hazard Ratio (HR)) X 100, where absolute efficacy of LAIV and IIV were calculated as the HR between LAIV or IIV and the control group, and relative efficacy was calculated as the HR between LAIV and IIV groups. VE was estimated for each study year using a Cox proportional hazards model (PH) [22] to account for seasonal variability in the risk of influenza virus infection and other time-varying covariates. Due to multiple study participants from same household, we also included random-effect term for household. (See S5_Sample_model_output). Observation period for each child began 14 days post-receipt of final vaccine dose each year. Children with at least 4 weeks of follow-up during the observation period for a given study year were included in the analysis until the earliest of the following censoring events: influenza virus infection (censored by virus type/subtype), last follow-up visit of that study year, or end of observation period.