Evaluating the effectiveness, impact and safety of live attenuated and seasonal inactivated influenza vaccination: protocol for the Seasonal Influenza Vaccination Effectiveness II (SIVE II) study.

INTRODUCTION: Seasonal (inactivated) influenza vaccination is recommended for all individuals aged 65+ and in individuals under 65 who are at an increased risk of complications of influenza infection, for example, people with asthma . Live attenuated influenza vaccine (LAIV) was recommended for children as they are thought to be responsible for much of the transmission of influenza to the populations at risk of serious complications from influenza. A phased roll-out of the LAIV pilot programme began in 2013/2014. There is limited evidence for vaccine effectiveness (VE) in the populations targeted for influenza vaccination. The aim of this study is to examine the safety and effectiveness of the live attenuated seasonal influenza vaccine programme in children and the inactivated seasonal influenza vaccination programme among different age and at-risk groups of people.

METHODS AND ANALYSIS: Test negative and cohort study designs will be used to estimate VE. A primary care database covering 1.25 million people in Scotland for the period 2000/2001 to 2015/2016 will be linked to the Scottish Immunisation Recall Service (SIRS), Health Protection Scotland virology database, admissions to Scottish hospitals and the Scottish death register. Vaccination status (including LAIV uptake) will be determined from the primary care and SIRS database. The primary outcome will be influenza-positive real-time PCR tests carried out in sentinel general practices and other healthcare settings. Secondary outcomes include influenza-like illness and asthma-related general practice consultations, hospitalisations and death. An instrumental variable analysis will be carried out to account for confounding. Self-controlled study designs will be used to estimate the risk of adverse events associated with influenza vaccination.

ETHICS AND DISSEMINATION: We obtained approval from the National Research Ethics Service Committee, West Midlands-Edgbaston. The study findings will be presented at international conferences and published in peer-reviewed journals.

TRIAL REGISTRATION NUMBER: ISRCTN88072400; Pre-results.