Accelerated development of vaccine benefit-risk collaboration in Europe


Start Date
End Date
IMI1 - Call 7
Grant agreement number

Type of Action: 
RIA (Research and Innovation Action)

IMI Funding
4 999 811
EFPIA in kind
5 108 448
1 236 241
Total Cost
11 344 500


Vaccines are one of the most effective public health measures out, saving some two to three million lives worldwide every year. However, in Europe, public distrust in immunisation programs is limiting high vaccine uptake, resulting in outbreaks of vaccine-preventable infectious diseases that had almost disappeared. Bringing together the European Centre for Disease Prevention and Control and the European Medicines Agency, as well as national public health and regulatory bodies, vaccine manufacturers and academic experts, the ADVANCE project will develop and test methods and guidelines in order to pave the way for a framework capable of rapidly delivering reliable data on the benefits and risks of vaccines that are on the market. This framework should both help regulators and public health authorities make decisions on vaccination strategies, and help maintain public confidence in immunisation as an effective public health tool to control infectious disease.

Immunisation prevents two to three million deaths worldwide every year from diseases such as diphtheria, tetanus, pertussis (whooping cough) and measles. Millions more are spared the long-term health consequences of vaccine-preventable infectious diseases; the WHO estimates that due to the Global Polio Eradication Initiative, five million people are walking today who would otherwise have been paralysed by the virus.

In Europe, one of the greatest barriers to the wider uptake of immunisation is distrust, among some sections of the public, of immunisation programmes. This is due largely to fears surrounding vaccine safety. In fact, serious side effects are very rare. Nevertheless, as vaccines are given to healthy people, public acceptance of the risk of any adverse reaction is much lower than for medicines designed to treat sick people; the trade-off between benefit and risk is different.

At the same time, some vaccines have been around for so long that many people have no personal experience of the diseases prevented, and so are unaware of just how serious the illness can be.

Restoring trust

Vaccines undergo rigorous safety testing before they are approved for public use. Currently, efforts to monitor the coverage, benefits and risks of vaccines after approval are rather fragmented.

The goal of ADVANCE is to review, develop and test methods, data sources and procedures which should feed into a blueprint of an efficient and sustainable pan-European framework that can rapidly deliver robust quantitative data for the assessment of the benefits and risks of vaccines that are on the market. Such a framework would allow regulators and public health authorities to make fast, informed decisions regarding vaccination strategies, and help to maintain public confidence in vaccines, particularly when questions are raised in the media about the safety of specific vaccines.

For example, such a framework could have more rapidly assessed and quantified the benefits and risks of the measles, mumps and rubella (MMR) vaccine, uptake of which fell in the UK in the years following the claim that it causes autism. Although that claim is now discredited and the doctor behind the claims has been struck off the medical register, uptake of the vaccine remains below the recommended threshold of 95%. A recent measles outbreak centred around the city of Swansea in south Wales (where vaccination levels were particularly low) saw over 1 200 people fall ill, of which 80 were hospitalised and 1 died.

The good news is that pilot studies have demonstrated the feasibility of setting up the components of such a framework in Europe, although turning it into a sustainable reality will not be easy. Data on vaccine-preventable diseases, vaccination coverage and adverse reactions to vaccines exist in many places and diverse formats, such as electronic health records, disease surveillance systems, and other healthcare databases. The ADVANCE team will have to identify and profile data sources capable of yielding rapid access to information on the burden of disease, vaccine coverage, and the benefits and risks of vaccines. Another challenge for the team will be developing the tools to link up this data and analysing it, taking into account the interoperability of the data sources and associated ethical and legal issues.

The project will run a number-of-proof of concept studies to ensure the platform meets the needs of its users. In order to cover the most common situations, these studies should ideally cover different age groups (e.g. infants / children, adolescents and adults / the elderly), different risk groups (e.g. pregnant women, people with other underlying health problems), and different vaccination scenarios (e.g. vaccinations given annually such as the flu jab, or vaccines introduced into the routine immunisation programme).

ADVANCE will also set out the framework’s core values, covering issues such as scientific best practice, a code of conduct, and rules for interactions between the different stakeholders.

In all aspects of its work, ADVANCE will build on the results of, and exploit synergies with, related projects. For example, the team will work closely with IMI’s EMIF project on data frameworks, and draw on the PROTECT project’s expertise in analysing and visualising the benefits and risks of medicines.

Collaboration is key

If the ADVANCE blueprint is to be adopted and implemented following the end of the project, it must be accepted by all stakeholders, including the European Centre for Disease Prevention and Control, national public health bodies, the European Medicines Agency, national regulatory agencies, health ministries, insurance companies, vaccine manufacturers, healthcare providers, and of course the general public. Collaboration between these diverse groups is very sensitive; by bringing them together around the neutral platform offered by IMI, ADVANCE is in a unique position to pave the way for a framework that will improve our ability to rapidly assess the benefits and risks of vaccines and help maintain public confidence in immunisation as a successful and effective public health tool to control infectious disease.

Achievements & News

IMI’s vaccine projects in the spotlight
May 2019

In the run-up to World Immunisation Week 2019, the IMI Programme Office caught up with three projects working in this important area.###

  • Vaccines are one of the most effective public health measures out, yet public distrust in immunisation programmes is limiting high vaccine uptake, resulting in outbreaks of vaccine-preventable infectious diseases that had almost disappeared. ADVANCE has paved the way for an open system for actively monitoring vaccine coverage, benefits and risks in Europe. Read more
  • Zoonoses are infectious diseases that can be transmitted to humans from animals (and vice versa). IMI's ZAPI project is working to create new platforms and technologies that will facilitate a fast, coordinated, and practical response to new infectious diseases as soon as they emerge. Read more
  • Every year, pharmaceutical companies develop vaccines designed specifically to combat the strains of influenza (flu) that are most likely to be in circulation the following winter. However, accurately predicting how much protection a new vaccine would actually offer against emerging virus types is far from easy. The FLUCOP project is developing tools to address this challenge. Read more

World Immunisation Week is organised by the World Health Organization at the end of April every year.

ADVANCE conference on vaccine benefit and risk monitoring
January 2019

The ADVANCE project will hold a conference entitled ‘EU ecosystem for monitoring of post-licensure vaccine benefit and risk: From ADVANCE to VAC4EU’ in Brussels, Belgium on 6 March 2019. ###ADVANCE brings together all major stakeholder groups interested in the post-marketing monitoring of the health benefits and risks of vaccines, and the consortium has demonstrated that the wealth of existing real-world health care data in the EU can be used to generate actionable evidence on vaccine coverage, benefits, and risks. This event will showcase the projects’ outputs; debate whether and how rapid evidence may help in reducing vaccine hesitancy; and present VAC4EU, the association which will implement the ADVANCE blueprint in the post-project phase. VAC4EU will allow EU research organisations to join the community and study network and collaborate in generating high quality and timely evidence on vaccine coverage, benefits and risks.

ADVANCE releases blueprint to support vaccine benefit/risk studies
November 2018

IMI’s ADVANCE project has published a blueprint of a framework to rapidly provide scientific evidence of the benefits and risks of vaccines that are on the market. The document is the culmination of the project’s work and is designed to help health professionals, regulatory agencies, public health institutions, vaccine manufacturers and the general public make more informed decisions on the benefits and risks of vaccines. ###Vaccinations are a highly successful public health intervention. However, as they are used primarily in healthy people (often children), expectations on their safety and effectiveness are particularly high. ADVANCE was set up to pave the way for a framework to make it easier and faster for people to assess vaccine benefits and risks. The project’s blueprint has two parts. Firstly, there is a comprehensive manual for the future use of the framework. This sets out the steps needed to use the framework, the tools that can be used, and how to disseminate results. The second part of the blueprint addresses the future sustainability of the network through four different scenarios. The blueprint was written by ECDC (European Centre for Disease Prevention and Control) based on the outputs from almost all work packages of ADVANCE. It has undergone a comprehensive consultation process with representatives of the main stakeholders interested in the assessment of benefits and risks of vaccines, including the ECDC Advisory Forum. It has also gone through a public consultation on ECDC website.

ADVANCE develops interactive dashboard to monitor vaccine benefit and risk
April 2018

The ADVANCE project has developed a web application with an interactive dashboard designed to make it easier to monitor the benefits and risks of vaccines in near real time. The tool is described in a paper in the journal Drug Safety. Once implemented, it would allow users to rapidly determine whether further regulatory or public health actions may be needed. ###The benefit-risk profile of vaccines that is determined initially in clinical studies may change during the vaccine’s life cycle, and needs to be further assessed once vaccines are on the market. In this study, the ADVANCE team assessed the feasibility and added value of using an interactive dashboard to monitor vaccine uptake, benefits and risks as well as composite benefit-risk measures. The dashboard was developed and demonstrated using simulated data mimicking the UK’s introduction of the rotavirus vaccine.  Feedback from stakeholders (including public health institutes, regulatory authorities, and pharmaceutical companies) revealed broad support for the dashboard, with users appreciating the interactive interface and the ability to visualise individual components. The stakeholders were however less in favour of the composite benefit-risk measures offered. The ADVANCE team concludes that ‘the proposed methodology is promising’ and they are now testing the dashboard with real-world data.

ADVANCE project publishes Code of Conduct to improve future vaccine studies
April 2017

Monitoring the benefits and risks of vaccines is a complex and critical activity which involves multiple participants. Decisions that have to be made at the planning stage of such studies are complex and numerous, which can prove challenging in situations where rapid action needs to be taken and a benefit/risk assessment is urgently needed.### To address that challenge, IMI’s ADVANCE project published a Code of Conduct: a document which contains a set of guiding principles for the multiple decisions that need to be taken at all stages of the planning, design, conduct and reporting of future studies. If adopted by all partners involved in a study, these recommendations will not only make it easier for the partners to collaborate, but will also give confidence to health professionals and the public about the quality of their results.

The ADVANCE Code of Conduct, now available in the journal Vaccine, was developed by members of a wide range of different organisations including regulatory and public health authorities, vaccine manufacturers and academic organisations. Its development was guided by three core and common values (best science, strengthening public health, transparency), and a review of existing guidance and relevant published articles. The document includes 45 recommendations in 10 topics: scientific integrity, scientific independence, transparency, conflicts of interest, study protocol, study report, publication, subject privacy, sharing of study data, and research contract. In the publication, the authors said they hope that ‘adoption of the ADVANCE Code of Conduct by all partners involved in a study will facilitate and speed-up its initiation, design, conduct and reporting'. The Code of Conduct is one of the four components of good practice guidance for vaccine studies, which will also include recommendations for good governance, quality management and communication on vaccine safety. This important deliverable of the ADVANCE project aims to pave the way for a European framework capable of rapidly delivering reliable data on the benefits and risks of marketed vaccines.

ADVANCE launches public consultation on its Code of Conduct
October 2015

Vaccine project ADVANCE has launched a public consultation on its draft Code of Conduct, which was developed to support the planning, initiation, design, conduct and reporting of observational studies in the field of vaccines.###

The Code of Conduct will also support interactions between different parties involved in studies on vaccines and provide confidence to health professionals and the public about the quality of their results.

The development of this Code of Conduct is co-led by the European Medicines Agency (EMA) within the ADVANCE project.

The draft Code of Conduct and details of how to submit feedback can be found online.

The consultation closes on 15 November 2015.

Participants Show participants on map

EFPIA companies
  • Glaxosmithkline Biologicals SA, Rixensart, Belgium
  • Janssen Vaccines & Prevention BV, Leiden, Netherlands
  • Merck Sharp & Dohme Corp, Whitehouse Station, New Jersey, United States
  • Novartis Pharma AG, Basel, Switzerland
  • Pfizer Limited, Sandwich, Kent , United Kingdom
  • Sanofi Pasteur SA, Lyon, France
  • Takeda Pharmaceuticals International AG, Glattpark-Opfikon (Zurich), Switzerland
Universities, research organisations, public bodies, non-profit groups
  • Aarhus Universitetshospital, Aarhus, Denmark
  • Agencia Espanola De Medicamentos Y Productos Sanitarios, Madrid, Spain
  • Agenzia Di Tutela Della Salute Della Val Padana, Mantova, Italy
  • Erasmus Universitair Medisch Centrum Rotterdam, Rotterdam, Netherlands
  • European Centre for Disease Prevention and Control, Stockholm, Sweden
  • Fundacio Institut Universitari Pera La Recerca A L'Atencio Primaria De Salut Jordi Gol I Gurina, Barcelona, Spain
  • Karolinska Institutet, Stockholm, Sweden
  • London School Of Hygiene And Tropical Medicine Royal Charter, London, United Kingdom
  • Rijksinstituut Voor Volksgezondheid En Milieu, Bilthoven, Netherlands
  • Sciensano, Brussels, Belgium
  • Statens Serum Institut, Copenhagen S, Denmark
  • Tampereen Korkeakoulusaatio Sr, Tampere, Finland
  • The European Medicines Agency, Canary Wharf, London, United Kingdom
  • The Open University, Milton Keynes, United Kingdom
  • The Royal College Of General Practitioners, London, United Kingdom
  • Universitat Basel, Basel, Switzerland
  • University Of Surrey, Guildford, United Kingdom
Small and medium-sized enterprises (SMEs)
  • P95 CVBA, Leuven, Belgium
  • Societa Servizi Telematici SRL, Padova, Italy
  • Synapse Research Management Partners SL, Barcelona, Spain
Third parties
  • Aarhus Universitet, Aarhus C, Denmark
  • Fundacion Española Para La Cooperacion Internacional Salud Y Politica Social, Madrid, Spain
  • Universitats-Kinderspital Beider Basel, Basel, Switzerland
Non EFPIA companies
  • Agenzia Regionale Di Sanita, Firenze, Italy
  • Medicines and Healthcare products Regulatory Agency, London, United Kingdom
Project coordinator
Miriam Sturkenboom
Managing entity
Jorgen Bauwens
Universitaet Basel
EFPIA coordinator
Vincent Bauchau
GlaxoSmithKline Vaccines