As soon as large-scale COVID-19 vaccination is possible, it is important to be able to monitor the efficacy and potential adverse effects of the different vaccines, says Miriam Sturkenboom. She is one of the Utrecht project leaders who, together with a host of European researchers, must ensure that Europe is prepared for this in good time.

Across the globe, over a hundred candidate COVID-19 vaccines are under development. About ten of these are already being tested on humans on a small scale, mainly in China and the US. As vaccines appear to be the only solution to the corona pandemic and the accompanying restrictions in daily life, there is enormous pressure to get them onto the market. "Development of a vaccine usually takes ten to fifteen years, now we must accomplish it within a year," says Miriam Sturkenboom, Professor of Observational Data Analysis working for UMC Utrecht. “Rather than skipping steps, developers complete every step at an accelerated pace. When a vaccine comes on the market some time from now, it will probably have been tested on only a few thousand people. Because of the short lead time, the study groups are limited in what they can do and certain subgroups, such as the elderly, pregnant women and children, will hardly be included in the study, if at all."

European infrastructure
The key question is what the benefit-risk balance of these vaccines will be, once they have been marketed. In other words: how effective are they when used for mass vaccination? Do they have adverse effects and if so, which? And: is the balance between efficacy and risks different for certain subgroups? Miriam: “In order to be able to answer these questions properly and quickly, you need a large-scale - European - infrastructure of data access, people, knowledge and tools that receives sufficient funding. When mass vaccination against COVID-19 becomes possible, everything must be ready to monitor the effectiveness and safety of those vaccines."

Dutch contribution
The ACCESS project (vACcine Covid-19 monitoring ReadinESS) serves to prepare Europe for this over the next six months. The European Medicines Agency (EMA) has concluded a contract with the European Pharmacoepidemiology & Pharmacovigilance Research Network and the Vaccine monitoring Collaboration for Europe (vac4eu.org). UMC Utrecht and Utrecht University (UU) are driving forces in these networks. As a reflection of this, the ACCESS project is headed by Miriam together with Olaf Klungel, Professor of Pharmacoepidemiologic Methods at UU. Incidentally, the Dutch contribution to the project is significant, with the National Institute for Public Health and the Environment (RIVM), side effects center Lareb and the PHARMA Institute also playing key roles.

100 million Europeans
Another key partner is the Vaccine monitoring Collaboration Network for Europe (VAC4EU). Miriam: “VAC4EU is a European non-profit association of which organizations can become a member. This is an effective concept for achieving long-term collaboration. At the moment, 22 organizations have already joined, and we're still receiving new applications. This creates a collaboration of public and relatively independent parties.” Through its members, VAC4EU has access to anonymous health data of over one hundred million Europeans, which can be analyzed in the same manner in the individual countries. “It is important that we can analyze and exchange large quantities of data quickly when we start vaccination. That way, we will know at any time where we stand."

Measuring methods
After a COVID vaccine has been approved by the EMA for the European market, the manufacturer will start distributing it in countries to which they have sold it. Miriam: "Every country has its own system for monitoring how effective and safe such a vaccine is, but most countries are too small to measure safety effectively. Say the Netherlands uses vaccine 1, Denmark uses vaccine 2 and Germany uses vaccines 3 and 4. We can learn far more from each other if we work together. At a European level, we can share expertise: some countries have excellent vaccine experts, other countries have outstanding specialists in analysis scripts.” Another advantage of collaboration concerns shared protocols. “Certain substances - what is known as the vaccine platform - may be the same in vaccine 1 and vaccine 4, but if everyone uses different measuring methods, the results cannot be compared very well. We are currently preparing protocols for how to measure the effectiveness and safety of a vaccine that can be used locally. That allows us to act quickly with the EMA and evaluate the benefit-risk ratio.”

Without vaccination
Today is the kick-off for the ACCESS project. The infrastructure as a whole should be in place in six months' time. At that time, the protocols must be ready, the required big data must be accessible and usable, people must have been trained and know how to find each other, and the necessary tools must be available (see, for example, the VAC4EU toolbox here). Preparations include calculations of how frequently certain clinical pictures occur normally, that is: without vaccination. Miriam: “We will calculate for 100 million people in Europe how often serious diseases occur without vaccination, such as acute respiratory syndrome, anaphylactic shock and Guillain-BarrĂ© syndrome. This is necessary to properly interpret the adverse effects that occur after introduction of the vaccines. This allows us to quickly see if the incidence of certain diseases is higher once we start mass vaccination, for instance of the elderly and healthcare workers. Together with the WHO and EMA we are currently preparing the list of disorders for which we want to do these calculations."
 
"This is, in fact, a European success story," says Miriam. The foundations for what we are able to do now were laid during the Mexican flu pandemic of 2009. At that time, the understanding arose that we really need a European infrastructure for monitoring vaccines. This infrastructure was developed and tested in recent years in the IMI-ADVANCE project, which ultimately resulted in VAC4EU. We are reaping the rewards now: what was developed then can now be implemented and expanded."