Title: Early estimation of pandemic influenza Antiviral and Vaccine Effectiveness (EAVE) - use of a unique community and laboratory national linked dataset
Funder: Chief Scientist Office, Scotland

Abstract: • Design: Primary Research - a large national retrospective observational cohort study of patients using a unique community, hospital and laboratory linked dataset. • Setting (PR): The PTI network of 40 general practices covers a five percent representative sample of the Scottish population (n=300,000). These practices receive an annual financial incentive to record all of their practice data electronically. Using the unique Community Health Index number, general practice patient level data will be extracted and linked to the SMR01 catalogue, which comprises of death data from the General Registers Office Scotland and in-patient hospital data for the whole of Scotland and also the Health Protection Scotland (HPS) dataset consists of laboratory confirmed cases of new pandemic influenza from throughout Scotland. In addition, Scottish laboratories (West of Scotland Specialist Virology Laboratory & Regional Virus Laboratory Specialist Virology Centre) will store all biochemistry samples (n~2000) from a subset of participating practices until the beginning of a new pandemic. • Target population (PR): 300,000 people of all ages registered with participating practices throughout Scotland. • Health technologies being assessed: The new pandemic influenza vaccination and antivirals (if available). • Measurement of outcomes: • Vaccine effectiveness will be measured using: Influenza positivity from virological swab data in vaccinated and unvaccinated patients stratified by ‘at-risk’ populations, age, sex and socioeconomic status. • Consultation for influenza-related morbidity from general practice data in vaccinated and unvaccinated patients stratified by ‘at-risk’ populations, age, sex and socio-economic status; • Mortality and influenza-related serious morbidity (e.g. influenza, pneumonia, COPD and cardiac related death and hospitalisation from SMR01 records) in vaccinated and unvaccinated patients stratified by ‘at-risk’ populations, age, sex and socioeconomic status; and • For patients with stored serology (and prior to the introduction of any vaccination) whether cross-reactivity occurs due to previous exposure to A/H1N1 or A/H1N1 vaccination, other pandemic influenza or other seasonal influenza vaccination or exposure. • Sample size: We plan to recruit 40 practices with a combined list size of 300,000 patients. Approximately 5% (n=15,000) of patients will be aged 0-5 years, 15% (n=45,000) aged over 65 years, and 30% under 65 years will be deemed to be in the at-risk category on the basis of existing illnesses.

Lay abstract: In the last century there were three pandemics (global epidemics) of influenza (1918-1919, 1957-58, 1968-1969) producing very large numbers of clinical cases and large numbers of deaths (an estimated 20-40 million, 1 million and 1 million deaths respectively) as the population had little immunity to the novel influenza viruses involved (H1N1, H2N2, H3N2 respectively). Immunisation programmes delivered in primary healthcare settings have been shown to be acceptable (as evidenced by previous high uptake rates) and effective, and this will therefore be the mainstay of disease prevention in any new influenza pandemic. Any new influenza vaccination will likely be targeted at those who are at increased risk of serious illness or death from influenza like illness. Observational studies can be used to estimate the effectiveness of healthcare interventions in situations where it is unethical and/or not feasible to mount more rigorous experimental studies; such is the case with the introduction of a new pandemic influenza vaccine. Observational studies can also assess the effects of healthcare interventions without influencing the care that is provided or the patients who receive it. Results from these studies are generalisable in that they can be used by other countries or regions to help guide public health policy. The potential novelty of a new pandemic virus requires that a high degree of vigilance at both the epidemiological and microbiological levels accompanies the implementation of a vaccine programme for the whole population. Policymakers will be reassured if: 1) early evidence can be gathered that the new pandemic vaccine is widely acceptable as evidenced by high uptake rates and is being distributed by primary care as a priority to those at most risk of adverse effects of the virus especially if some groups are more susceptible than others e.g. children, the elderly, the most socioeconomically deprived or pregnant women and those deemed to be at-risk on the basis of existing illnesses and 2) if the vaccine is known, at an early stage, to be effective in preventing influenza like illness and death. The setting for this project will be in 40 general practices based throughout Scotland. These practices have about 300,000 people registered with them. By extracting the relevant de-identified electronic patient information from general practice, which includes age, sex, illness data, vaccination and prescribing information and linking this with laboratory data of patients with suspected new pandemic influenza and information on previous exposures to past pandemic A/H1N1 influenza and/or seasonal influenza and also information on death from the General Register for Scotland dataset; from this compiled dataset, we will be able to determine the: 1) Uptake of the new pandemic vaccine by the relevant at risk populations; 2) The identification of susceptible groups in the population to help target the vaccination; 3) Reduction in the expected incidence of influenza related serious morbidity and mortality in the most susceptible risk groups, since this is the major rationale behind the immunisation policy; and 4) Effectiveness of the pandemic vaccine/antivirals in the whole population. Permission to use similar linked data for research purposes has been previously obtained. We are confident that we will also be able to obtain the necessary approvals from the Information Services Division’s Privacy Advisory Committee (who oversee linkage of NHS data) the general practices and Research Ethics Committee. Our team has the necessary expertise and experience to undertake this work to an international standard in a timely fashion. Specifically: Dr Colin Simpson (principal investigator) is a senior research fellow and an expert in data linkage and the use of primary care data for epidemiological research. Dr Jim McMenamin is a clinical epidemiologist, a consultant in respiratory medicine and has expertise in the evaluation of Vaccine Effectiveness. Professor Chris Robertson is head of statistics at Health Protection Scotland and professor in statistics at the University of Strathclyde. Dr Nazir Lone is a intensive care and respiratory clinician. Professor Lewis Ritchie is a professor of medicine and the Chair of the Scottish H1N1 Immunisation Delivery Group. Professor Aziz Sheikh is a professor of medicine has an expertise in the use of primary care data for research and carrying out health technology assessments. The University of Edinburgh will sponsor the project and HPS and Department of Mathematics and Statistics (Strathclyde University) teams will act on a consultancy basis, invoicing Edinburgh on completion of work. Dr Simpson will be co-ordinating the project, and the co-applicants will also contribute some of their time towards the completion of the project. The eHealth Research Group (University of Edinburgh) and HPS will ask for permissions to extract and link data from the sentinel general practices. We are exploring a commercial system (Albasoft’s ESCRO) for data extraction and have provided a prelinary cost for this. The Department of Mathematics and Statistics University of Strathclyde will assist HPS with co-ordination of laboratories, the setting up of standard operating procedures and the monitoring and also carry out the statistical analyses and help with the write-up of the final report. In addition Professor Bill Carman and Dr Walt Adamson from the West of Scotland Specialist Virology Centre (Gartnaval General Hospital) will provide expert advice and help co-ordinate serology storage and testing.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: INFECTION