A pandemic is a fast-moving situation, and as the H1N1 virus began to spread throughout the world in 2009, pharma companies leapt into action to start the process of developing vaccines. In late 2009, the first vaccines began to be authorised by the European Medicines Agency, the EU body whose job it is to give the green light to drug manufacturers to market new medicines. As with any new vaccine, clinical studies carried out by the pharma companies before the vaccines were approved had produced lots of data on the safety, tolerability and efficacy and vaccines. However, clinical studies don’t tell us everything we need to know about the effect of a vaccine because they’re limited, both in size and diversity. That’s why the authorities usually require the drug maker to carry out other studies ‘post marketing’ i.e. once the vaccine has been rolled out, so that they can continue to gather evidence about its safety and its effectiveness in a much wider swathe of the population.
Traditionally, efforts to monitor the coverage, benefits and risks of vaccines after approval have been fragmented. Once the vaccines are approved, certain data are inaccessible to the pharma companies because they are not within the companies’ control. This is true for data on effectiveness, though not for data on adverse events, since each company has its own database of post-marketing adverse event reports and many also have access to some real-world databases. While these are accessible, it is however sometimes not sufficient and additional data may be needed. The custodians of this data are disease surveillance bodies i.e. public health institutes and the pan-EU European Centres for Disease Control (ECDC), who are responsible for collecting information about diseases and vaccine effectiveness.
In order to maintain a reputation for independence, the ECDC and national public health bodies have traditionally been reluctant to build a relationship with pharma companies. This is understandable; the public’s willingness to take a vaccine can largely depend on the level of trust they have in the authorities, and the perception of independence is crucial in this regard. However, without access to these data, the pharma industry is unable to produce this post-marketing evidence. Beyond the problems this poses for the industry, the lack of solid, scientific evidence of the impact of a vaccine on a broad scale hampers public health bodies’ ability to detect adverse effects and other rare events in the population, in turn delaying their reaction to such events. This, too, is bad for public trust in vaccines.
Recognising that this way of doing things was unsustainable, ADVANCE set about conceiving a new system that would not only bring all these disparate groups around the table, but crucially, give them access to scientific, independent and transparent information, quickly and easily, so that they can feed their own decision-making and vaccine strategies. After two years of negotiation, ADVANCE were able to set up a consortium made up of the European Medicines Agency, the ECDC and other public health institutes, academic groups, and almost all vaccine manufacturers in Europe.
Having drawn up the best practice guidelines for collaboration between the different players, ADVANCE identified and made profiles of the different data sources that are capable of yielding rapid access to vaccine information – such as electronic health records, disease surveillance systems, and other healthcare databases. They also went about establishing exactly what kind of evidence different stakeholders would need access to, i.e. background rate of events (events that are temporally associated with but not caused by vaccination), vaccine coverage, whether the vaccine seems to work, and safety data. They then built new tools to link up this data and analyse it, taking into account the interoperability of the different systems, and ran their own test cases – proof of concept studies to make sure the tools worked.
The ADVANCE partners decided to set up an international non-profit called VAC4EU, analogous to the US body DataLink/Sentinel, that now stands ready to respond rapidly and reliably to questions from manufacturers, regulators and public health authorities about the impact of a vaccine on a given population, based on real-world data. VAC4EU does not pool all data from EU countries in one place; rather, the data is generated locally in each country or region, and local teams input their own data locally in a standardised, structured way. They then have the ability to run a programme that analyses the data and comes up with standardised results and to pool their evidence with other countries to get a more zoomed-out view.
There is a lot of heterogeneity in Europe’s health care systems, not to mention languages, and yet ADVANCE has definitively demonstrated that despite all these differences, a Europe-wide system can work; the VAC4EU platform can deliver robust data that not only deals with this heterogeneity, but can even exploit it. For example, European countries may be using different vaccines, having negotiated contracts independently with several manufacturers. Working in a standardised allows them to compare the different the effects of the different vaccines, giving them a chance to study the evidence for the benefits and adverse events of the different schemes on a much bigger scale. This not only has the effect of building collaboration between countries but also builds capacity within the countries themselves, helping spark new collaborative relationships between public health institutes and the national regulators.
Working on a European level also makes it possible to compare vaccine data between continents; for example, none of the vaccines that were deployed in the U.S. in the wake of the 2009 H1N1 pandemic were adjuvant vaccines (adjuvants are added to vaccines to or enhance immune responses). In Europe, on the other hand, a number of adjuvant vaccines were used. It would be very informative to be able to compare the evidence both continents on effectiveness and adverse effects.
The VAC4EU platform is designed to promote the best practices developed in the ADVANCE project related to collaboration between the different stakeholders, as well as study conduct, ethics, and privacy protection relating to the capture, sharing and trustworthy generation of real-world health data. It is intended to stimulate scientific discussions and keep up with new methods and other important developments. It can provide training, access to a unique vaccine expert community and study network that boosts links and consensus between the regulators, public health institutes, researchers, and vaccine manufacturers, as well as patient and citizen groups and healthcare providers.
With VAC4EU, all the necessary infrastructure is in place to carry out a pan-European monitoring of the effects of the COVID vaccines when they are rolled out in the population, helping to maintain public confidence in immunisation as an effective public health tool to control infectious disease. Limited funding has been made available from the EMA.