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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
  1. Colin R Simpson1,
  2. Nazir I Lone1,
  3. Kimberley Kavanagh2,
  4. Chris Robertson2,3,
  5. Jim McMenamin3,
  6. Beatrix von Wissmann3,
  7. Eleftheria Vasileiou1,
  8. Chris Butler4,5,
  9. Lewis D Ritchie6,
  10. Rory Gunson7,
  11. Jürgen Schwarze8,
  12. Aziz Sheikh1
  1. 1Asthma UK Centre for Applied Research, Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, UK
  2. 2Department of Mathematics and Statistics, University of Strathclyde, Glasgow, UK
  3. 3Health Protection Scotland, Glasgow, UK
  4. 4Nuffield Department of Primary Care Health Sciences, Oxford University, New Radcliffe House, Radcliffe Observatory Quarter, Oxford, UK
  5. 5Cardiff University, Institute of Primary Care and Public Health, Cardiff, UK
  6. 6Centre of Academic Primary Care, University of Aberdeen, UK
  7. 7West of Scotland Specialist Virology Centre, Glasgow, UK
  8. 8Child Life & Health and MRC-Centre for Inflammation Research, The University of Edinburgh, Edinburgh, UK
  1. Correspondence to Dr Colin R Simpson; c.simpson{at}


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.


This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See:

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  • Contributors CRS, NIL, KK, CR, JM, BVM, LDR, RG and AS contributed to the conception of the study. All authors contributed to the study design. All authors contributed to drafting the protocol. All authors revised the manuscript for important intellectual content. All authors gave final approval of the version to be published.

  • Funding This project was funded by the National Institute for Health Research Health Technology Assessment Programme (project number 13/34/14). EV was supported by the Chief Scientist Office of the Scottish Government under grant (AUKCAR/14/03). This work is carried out with the support of the Asthma UK Centre for Applied Research (AUK-AC-2012–2001) and the Farr Institute.

  • Disclaimer The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Health Technology Assessment programme, NIHR, NHS or the Department of Health.

  • Competing interests None declared.

  • Ethics approval National Research Ethics Service Committee, West Midlands—Edgbaston.

  • Provenance and peer review Not commissioned; externally peer reviewed.