Chapter 5: Major Multi-Stakeholder Initiatives — Defining the Future of COVID-19 Observational Research



Brief Description of the COVIDRIVE initiative and data

COVIDRIVE is the newest multi-stakeholder COVID-19 RWD initiative covered in this chapter. Initiated at the end of 2020, this public-private partnership aims to address the need to continuously monitor COVID-19 vaccination programs to assess brand-specific COVID-19 vaccine effectiveness, supporting vaccine companies in meeting their regulatory obligations in a consistent manner as well as public health institutes in Europe.

Core requirements for the Risk Management Plan (RMP) for COVID-19 vaccines for the EMA state that “effectiveness studies should be included” in the RMP and that the Marketing Authorisation Holder (MAH) should “make use of the established EU efforts that can provide brand-specific,” reliable and timely data.81 COVIDRIVE fits this recommendation, leveraging an existing influenza vaccine effectiveness platform: Development of Robust and Innovative Vaccine Effectiveness (DRIVE).82 DRIVE is a 5-year Innovative Medicine’s Initiative (IMI) project, conceived as a proof of concept by EMA to develop a public-private partnership platform providing yearly brand-specific effectiveness estimates for all influenza vaccines and to be used by vaccine companies to fulfill their regulatory obligations. Data has been collected in each influenza season since 2017 from an expanding network of hospitals and general practitioners in Europe. Throughout the project, DRIVE has developed a governance framework fostering transparent collaboration between public and private partners for high-quality research and vaccine performance evaluation.

Key assets leveraged in COVIDRIVE are an efficient study platform and a transparent public-private mechanism with functioning governance including shared decision-making, mutualization of resources leveraging public and private capacities and funds, collaboration in methods, independent study conduct and scientific committee for results review, high data quality standards, and regulatory pathways.

As a public-private partnership, COVIDRIVE includes public institutions, small-to-medium enterprises, and vaccine companies. To date (May 13, 2022), non-industry partners include the Foundation for the Promotion of Health and Biomedical Research in the Valencian Area (FISABIO) from Spain, P95 from Belgium, and The Finnish Institute for Health and Welfare (THL). Vaccine company partners include AstraZeneca (UK), CureVac (Germany), GSK (Belgium), Janssen (Belgium), Moderna (US), Novavax (US), Sanofir (France), and Valneva (France). The consortium is open to new partners (e.g., public health institutes, industry, small-to-medium enterprises, academia) and new European study sites. This partnership offers great opportunities to mutualize health care practitioners’ resources between companies and leverage existing public capacities across Europe, joining forces for a better understanding of COVID-19 disease and vaccine performance. The first COVIDRIVE study monitors for variants of concern and helps provide answers to the critical questions relating to COVID-19 vaccine effectiveness, including duration of protection of the different vaccines, impact of additional vaccine doses, and different vaccine combinations. Beginning with initial recruitment of patients in September 2021 from 12 hospitals in Spain and Italy, COVIDRIVE is currently planned for 2 years and is designed to quickly expand to other countries across Europe. AstraZeneca (UK) and Janssen (Belgium) are the first vaccine companies in this partnership to monitor the effectiveness of their respective vaccines. A study team composed of COVIDRIVE partners supports the study sites in their data collection, and the first interim results are expected within 6–12 months from recruitment initiation. All scientific results will be reviewed by an Independent Scientific Committee.

COVIDRIVE and COVID-19 observational research: European framework and data, vaccine effectiveness

COVIDRIVE data are collected from hospitals and potentially also primary care centers, often building on existing public health surveillance systems and sites. National register data can also be used in countries where it is available. The network for this observational initiative is expected to include more than 40 hospitals and 500 general practitioners in 12 European countries: Austria, Belgium, Croatia, Finland, Germany, Iceland, Italy, Netherlands, Poland, Romania, Spain, and the UK.83

Each study site is responsible for the collection, validation, and management of participant-level study data. Participating sites follow a master study protocol and related study procedures to ensure high quality standards. Because data collection and source documentation will differ across sites, data flow and management are documented in detail. Participant-level data are locally transformed to conform to a study-specific common minimum data set. The study site performs quality checks and processes any findings accordingly, with sufficient documentation to ensure transparency and reproducibility. The study-specific common minimum data set, composed of data uploaded by the study sites, will be stored on a dedicated secure server; the COVIDRIVE Research Server (CRS), following General Data Protection Regulation (GDPR) compliance requirements.

COVIDRIVE Case Studies

COVIDRIVE’s initial studies aim at monitoring COVID-19 vaccine effectiveness against severe disease for specific vaccine brands.

These initial vaccine effectiveness studies are using a hospital-based case-control study with test-negative control design.84,85 Additional studies addressing other aspects related to the evaluation of COVID-19 vaccine benefits are envisioned with contributions by study sites and COVIDRIVE partners.

Current areas of interest include: duration of vaccine protection (mid- and long-term), characterization of circulating variants and vaccine effectiveness against disease caused by those variants and newly emerging SARS-CoV-2 strains, effectiveness over calendar time (with date of hospital admission serving as a proxy for changing genetic variants of the virus), effectiveness against severe COVID-19 disease, and effectiveness in special risk groups such as immunocompromised, frail individuals or subjects with chronic conditions or existing comorbidities.

The exposure of interest and vaccination status (including brand information and date of vaccination[s]) are collected via vaccination registries, vaccination cards, and medical records (depending on country/region). Batch information will be additionally collected when available. Context information on public health guidance, national/regional immunization recommendations including vaccines recommended by authorities, SARS-CoV-2 genetic variant circulation, and COVID-19 vaccine label information will also be collected.

Potential confounders and effect modifiers collected at all sites include: age, sex, history of medical diagnosis for selected morbidities of interest (asthma, lung disease, cardiovascular disease, hypertension, chronic kidney disease, type 2 diabetes, cancer, immunodeficiency), body mass index, vaccination against pathogens causing COVID-19 like symptoms (influenza, pneumococcus), calendar time, and previous SARS-CoV-2 infection. When available, information on precautionary health behaviors (e.g., wearing face masks, using hand sanitizer, going to public places), socio-economic variables and/or ethnicity, being a health care worker, residence in a long-term care facility residence, and smoking history will be collected.

COVID-19 vaccine effectiveness will be estimated with random-effects meta-analysis of site-specific estimates or Generalized Estimating Equations (GEE). The site-specific estimates will be obtained in logistic regression models, adjusting for the confounders. A final study report will be written for each of the individual COVID-19 vaccine brands of interest. The protocol and study reports are posted on the European Union electronic register of Post-Authorisation Studies (EU PAS register)84,85 and the study results will be published in peer reviewed open-source international journals. Study sites will remain owners of their subject level data.

Study limitations may include low sensitivity and specificity of the Reverse Transcription Polymerase Chain Reaction (RT-PCR) test, with a bias towards underestimating the effectiveness that is proportional to SARS-CoV-2 positivity rates within the patients meeting the case definition. The study protocol84,85 posted in the EU PAS register provides additional details.

COVIDRIVE impact and perspective

Dr. Javier Díez-Domingo, Head of the Vaccines Research department of the Foundation for the Promotion of Health and Biomedical Research (FISABIO) foundation and COVIDRIVE co-coordinator, says the first priority of the initiative is to examine COVID-related hospitalization as an outcome.86 “Hospitalizations were one of the main reasons for national and regional governments to impose public health measures such as shutdowns, social distance, and wearing of masks to relieve the disease burden on the health care systems. Producing accurate and timely information on how well the different COVID-19 vaccines protect against hospitalizations and remain protective over time is essential to successfully manage the pandemic.”86

Thomas Verstraeten, co-coordinator of COVIDRIVE and CEO of P95 (a company that provides consultancy services) says “The current COVID-19 pandemic highlights the need for a public-private collaborative environment to generate vaccine effectiveness data to advise the design of national immunization programs and to fulfil the effectiveness requirements established by the regulatory authorities.”86

Laurence Torcel-Pagnon, a key contributor to COVIDRIVE and evidence generation partnership expert at Sanofi, indicates that “the consortium strives at developing a framework to leverage the secondary use of the collected data to address future research questions to advance knowledge on COVID-19 disease and related vaccines performance.” She also emphasizes the importance of multi stakeholder partnerships including public health organizations, academia, industry, and research organizations to maximize the value of fit-for-purpose RWD to address today’s and tomorrow’s COVID-19 research questions.