Title: Seasonal Influenza Vaccination Effectiveness II (SIVE II): Use of a large national primary care and laboratory-linked dataset to evaluate live attenuated and trivalent inactivated influenza vaccination effectiveness
Funder: Chief Scientist Office, Scotland

Abstract: Design: A national longitudinal retrospective observational study. Vaccine effectiveness will be derived from linked virological swab data, using a nested case-control study design (test negative) and adjusted for covariates including comorbidities, healthcare utilisation (i.e. any cause primary care and hospital consultations – including out-patient attendance and admission) and previous vaccination. Setting: A national laboratory and hospital/mortality linked primary care database. Strategy for reviewing literature (Primary or Modelling): A structured literature review using Pubmed, Medline, Embase, Scopus and Google Scholar (all articles published to January 2013). The search terms include “live attenuated influenza vaccine, trivalent inactivated influenza vaccine, and effectiveness”. Target population: Primary analysis will be performed on children and young adults between two and 17 years (targeted for live attenuated influenza vaccine), registered with 500 primary care practices (including all sentinel influenza surveillance practices) in Scotland. Data from 2013 to 2015 (two pooled seasons providing one million patient years of data) will be linked to the Health Protection Scotland virology database (Reverse Transcriptase Polymerase Chain Reaction [RT-PCR] tests collected in influenza season) and national hospital/mortality datasets using the Community Health Index number. Health technologies being assessed: We will evaluate the live attenuated influenza vaccine. Measurement of outcomes: Primary outcome is RT-PCR laboratory confirmed influenza (cases sub-typed as A(H1N1)pdm09, A/H1N1, A/H3N2 or B). Sample size: Using data generated from the SIVE project [09/200/37] we estimate a vaccination rate of 40% amongst children targeted for receipt of LAIV and a swab positivity rate of 20% among the unvaccinated. This gives an 80% power to detect a VE of 21% based upon 3000 swabs over two seasons (NB additional funding has been released to increase swabbing in children). Project timetables including recruitment rate: Month 12 – Governance and ethics approvals, practice recruitment, data specification, statistical modeling, drafting of methods protocol. Month 13 – Publication of protocol. Month 20 Test data collection and linkage. Month 20 – Draft early estimates of LAIV uptake/vaccine effectiveness available. Month 25 – Full data extraction, statistical analysis. Month 30 – Final report completed. Expertise in team: Our team, which includes experts in medical statistics, data linkage, epidemiology with a proven track record in carrying out vaccine effectiveness studies. The PIs Dr Colin Simpson and Dr Nazir Lone have considerable expertise in the use of primary care data and data linkage and has successfully led previous NIHR projects in evaluating vaccine programmes. Ms Ehrlich is a retired teacher and experienced public and patient involvement lead. Dr Jim McMenamin and Professor Chris Robertson have considerable expertise in the evaluation of vaccine programmes. Professor Sir Lewis Ritchie has led the implementation of several new national immunisation programmes. Professor Aziz Sheikh is a Professor of Primary Care Research & Development is a methodologist has long-standing expertise in the use of linked primary care based datasets for undertaking epidemiological and public health research.

Lay abstract: In Scotland a new policy on influenza is due to be introduced to ensure more people are vaccinated. A new type of influenza vaccine (live attenuated influenza vaccine) is being introduced this year to all children between 2 and 17 years. However, it can be difficult to evaluate any changes in health as a result of new immunisation programmes given that randomised controlled trials of the vaccine are impractical and can also be seen as unethical. These policy changes therefore are typically not evaluated, making it difficult to inform future policy in this field. Observational studies, using information from electronic health records, can be used to assess the effects of healthcare interventions without influencing the care that is provided or the people who receive it. Results from these studies are likely to be both valid and generalisable if carefully undertaken and interpreted. This might include, for instance, being aware of biases such as the ‘healthy vaccine effect’ - if vaccines are given to healthier individuals, this could lead to overestimates of the effectiveness of the vaccine. Observational studies can also be improved by including measures of the effect that the influenza vaccines have in improving very specific measures of influenza, such as the numbers of influenza cases confirmed by a laboratory. We have a substantial track-record of evaluating vaccine programmes using information from linked healthcare electronic records [SIVE: bmjopen.bmj.com/content/2/2/e001019.full?]. We now plan to conduct the world’s first evaluation of this new policy change. We will also evaluate the effectiveness of the vaccine programme for other groups where the evidence available is limited (e.g. people 65 years and older and people with asthma). We will extract information, about influenza vaccination and other relevant health information, from 500 general practices (half of the practices in Scotland) and the Scottish Immunisation Record System. We aim firstly to link these data to information on swabs collected by general practitioners (and from hospitals) to detect influenza in children from 2013 and all people from 2000 to 2015 and stored by Health Protection Scotland and then also link information to hospital and death records. This will provide us with sufficient information to carry out the evaluation. With support of The electronic Data Research and Innovation Service (eDRIS) and The Farr Institute, the Asthma UK Research Centre and Scottish Immunisation Programme – and our prior experiences with undertaking NIHR funded SIVE, VIPER and EAVE projects – we are ideally placed to undertake this work and ensure rapid translation into future policy developments.

Research activity codes: 3.4 VACCINES
Health categories: INFECTION