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Development of Robust and Innovative Vaccine Effectiveness

Periodic Reporting for period 4 - DRIVE (Development of Robust and Innovative Vaccine Effectiveness)

Reporting period: 2020-07-01 to 2021-06-30

Influenza is a major public health problem: each year, up to 50 million people fall ill with seasonal influenza in the EU and up to 70.000 die from it. Vaccines are the cornerstone of preventing influenza but their effectiveness can vary from year to year and across recipient groups. The European Medicines Agency (EMA) has requested effectiveness evaluation for all individual influenza vaccine brands, a task that demands international cooperation between public health institutions and vaccine manufacturers.

DRIVE (Development of Robust and Innovative Vaccine Effectiveness) was formed to establish a sufficiently sized network to generate robust, brand-specific effectiveness estimates for all influenza vaccines used in the EU. The data generated through DRIVE is expected to increase the understanding of influenza vaccine effectiveness, lead to enhanced monitoring of influenza vaccine performance by public health institutes and allow manufacturers to fulfil the requirements of the European Medicines Agency (EMA). DRIVE also aims to develop a sustainable and transparent governance model for public-private partnerships.
DRIVE started in July 2017. In three years it has laid down the study governance needed for a multicentre evaluation of influenza vaccine effectiveness, tested this in practice during the seasonal influenza epidemics of 2017/18, and perform actual analyses in the 2018-19 and 2019-2020 season. DRIVE has also accomplished a number of supportive tasks that enhance the studies and their governance.

To support the studies, DRIVE developed novel study protocols and statistical analysis plan. Other important accomplishments include a multi-stakeholder research agenda, guidelines for interpreting IVE results, report templates, Standard Operating Procedures, IT infrastructure for data collection & analysis, a data management plan, a report on the sources of vaccine brand data, a communications plan, and a website. Annual call for tenders yielded several high-quality proposals from sites willing to join DRIVE for the influenza season 2021-22 and will contribute to the constant expansion of DRIVE research platform in the coming season.

DRIVE study platform is constantly expanding and currently includes 13 sites from 8 different European countries. DRIVE’s main objective in its first pilot season (2017/2018) was to establish and test the feasibility of the new multi-country platform using a limited number of sites. In the following two seasons, an IT platform for data collection was developed, protocols and statistical analysis plan were improved and assessment of IVE results and site selection by the Independent Scientific Committee was fine-tuned to ensure transparency.

Test-negative design (TND) case-control studies (4 in primary care and five in hospital) were conducted in six countries in Europe during the 2018/19 season. While sample size from the pooled TND studies was still too low for precise (brand-specific) IVE estimates, the network has approximately doubled in size compared to the pilot season. The detailed reports are available in DRIVE website and the results from 2018/2019 season were open access published in Vaccine: DOI: 10.1016/j.vaccine.2020.07.063.

For the 2019/20 season, 4 primary care-based Test Negative Design (TND) studies (Austria, England, Italy), 8 hospital-based TND studies (Finland, France, Italy, Romania, Spain) and one register-based cohort study (Finland) were conducted. In 2019/20, DRIVE estimated IVE for 8 out of 11 vaccine brands available in the market in Europe and obtained the first precise brand-specific estimates from TND studies. Four precise estimates were obtained, two were for any vaccine, and two were brand-specific. Additionally, precise brand-specific estimates were obtained from the register-based cohort study for the two vaccines used in Finland. All these estimates showed a protective effect of influenza vaccination. Despite the challenges faced during the COVID-19 outbreak, the low case numbers in this relatively mild influenza season and low vaccine coverage in certain age groups, DRIVE obtained several precise brand-specific IVE estimates for the 2019/2020 season.

For the 2020/21 season, DRIVE faced its fourth influenza season with the uncertainties posed by the COVID-19 pandemic and the unforeseen changes in the influenza circulation patterns. An expanded study network involving 13 research sites in 8 European countries, covering 24 hospitals and more than 500 general practitioners worked together to collect the data necessary for the DRIVE studies and adapt to the particularities of the season 2020/21. In a season marked by the absence of influenza circulation in Europe, the objectives of DRIVE for the 2020/21 season have only been partially fulfilled, as not enough lab-confirmed influenza cases were recruited in DRIVE dataset. Thus, no brand-specific or overall IVE estimates could be obtained for the TND studies, and only overall IVE estimates for the Finnish cohort study were produced. However, the latter could not be interpreted due to large confidence intervals. DRIVE dataset has captured 7 out of these 9 marketed brands, demonstrating DRIVE’s ability to gather information on multiple influenza vaccine brands across Europe.
DRIVE is expanding the network of influenza vaccine studies in the EU but also seeks to improve its quality. The protocols and statistical analysis plans aim to harmonize data collection and provide scientifically robust results. A literature review on bias and confounding factors and how to take them into account in studies allowed fine-tuning of the protocols. DRIVE is also looking into novel and innovative ways to assess vaccine effectiveness. There is a quality control committee that supervises the quality of the procedures followed within DRIVE, as well as the data retrieved.

DRIVE is working in an unprecedented way to map the vaccine types and brands used in Europe with the aim of applying this information to ensure that all influenza vaccine types and brands available in the EU are eventually covered by the evaluation. The governance model developed over the 5 years’ project will provide valuable suggestions for future public-private partnerships. Key performance indicators of scientific independence, integrity and transparency have been developed, and these and other metrics will be developed and applied during the course of the project.
DRIVE model graphic
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