Periodic Reporting for period 4 - PrIMAVeRa (Predicting the Impact of Monoclonal Antibodies & Vaccines on Antimicrobial Resistance)
Période du rapport: 2024-11-01 au 2025-10-31
Predicting the Impact of Monoclonal Antibodies & Vaccines on Antimicrobial Resistance (PrIMAVeRA) aims to develop mathematical models and an epidemiological repository to assess the impact of vaccines and monoclonal antibodies (mAbs) on antimicrobial resistance (AMR).
AMR causes a high burden of disease that can be reduced by preventing infections through implemention of vaccines and mAb. These well-known strategies are challenging to put in practice due to limited knowledge about the most important target populations, or target pathogens, high development costs, and complex development process. PrIMAVeRa tries to fill this gap by modelling which pathogens, infections and populations result in the highest AMR burden, and through which healthcare services priority vaccines and mAb could be delivered. The final product will be a planning tool to identify the most cost-effective vaccine targets and mAb strategies according to the country-specific AMR burden.
To use limited resources most effectively, it is crucial to be able to rank potential interventions against AMR according to cost-effectiveness. The PrIMAVeRa project aims to provide policymakers with the comprehensive models necessary to provide this capability.
AMR causes a high burden of disease that can be reduced by preventing infections through implemention of vaccines and mAb. These well-known strategies are challenging to put in practice due to limited knowledge about the most important target populations, or target pathogens, high development costs, and complex development process. PrIMAVeRa tries to fill this gap by modelling which pathogens, infections and populations result in the highest AMR burden, and through which healthcare services priority vaccines and mAb could be delivered. The final product will be a planning tool to identify the most cost-effective vaccine targets and mAb strategies according to the country-specific AMR burden.
To use limited resources most effectively, it is crucial to be able to rank potential interventions against AMR according to cost-effectiveness. The PrIMAVeRa project aims to provide policymakers with the comprehensive models necessary to provide this capability.
In the first year, partners focused on the literature search. Protocols for five systematic reviews (SRs) were developed and uploaded to the International Prospective Register of Systematic Reviews (PROSPERO): 1) frequency measures of healthcare-associated infections and antimicrobial resistance (AMR), 2) AMR-associated health outcomes, 3) AMR-associated economic outcomes, 4) existing mathematical models for AMR, and 5) obtaining individual-level data. Potential databases were identified, articles screened and extracted, and initial contact was made to request data access. Discussions were advanced on making both aggregated and individual-level data publicly available through the EPI-Net repository. The project management structure was established, the project website was launched, and the Scientific Advisory Committee (SAC) was set up.
In the second year, work concluded on all four systematic reviews, and manuscripts were submitted for publication. Aggregated data and visualizations of meta-analyses on the pathogen-specific impact of AMR were made publicly available via the EPI-Net platform: https://epi-net.eu/primavera/about/(s’ouvre dans une nouvelle fenêtre). Data gaps were identified and discussed with partners to inform further actions. These gaps also guided work on a research prioritization agenda, for which a Delphi exercise was performed and a manuscript drafted. A theoretical model framework was advanced, with three case studies selected for the population models to be developed. Relevant data were identified, collected, and evaluated. More than 100 database owners were contacted, and the infrastructure to gather and share the data publicly was implemented, with the legal process to complete data-sharing agreements ongoing.
During the third year, five papers were published based on the systematic reviews and research conducted for model development. Work on the case studies was concluded, with two chosen to be advanced in subsequent project activities. A second search for additional patient-level data was performed, and third parties can now apply for access to individual-level patient data on the ECRAID-Base EPI-Net platform: https://epi-net.eu/primavera/data-availability/(s’ouvre dans une nouvelle fenêtre). Work also began on cost-effectiveness analyses, as well as model evaluation and sustainability planning, with results expected to be reported over the following two years.
In the fourth year, two papers were published based on systematic reviews and model development research, and two additional manuscripts addressed future priorities for AMR research and challenges in data sharing. Efforts to gather anonymized individual-level patient data continued, resulting in the collection of 14,058 patient-level records from 19 of the 34 resistance–pathogen–infection groups, out of 196 eligible studies contacted. Three case studies—focusing on E. coli, S. aureus, and K. pneumoniae—were selected for programming language implementation and the development of a joint code repository. Work on cost-effectiveness analyses, model evaluation, and sustainability continued, with final results expected in the project’s last year.
To ensure continuous progress, the consortium held three annual meetings, four teleconferences with the SAC, and three workshops to advance model development. Dissemination activities included press releases and social media posts aligned with project milestones and outputs, which contributed to increasing project visibility and promoting the results to the broader scientific community.
In the second year, work concluded on all four systematic reviews, and manuscripts were submitted for publication. Aggregated data and visualizations of meta-analyses on the pathogen-specific impact of AMR were made publicly available via the EPI-Net platform: https://epi-net.eu/primavera/about/(s’ouvre dans une nouvelle fenêtre). Data gaps were identified and discussed with partners to inform further actions. These gaps also guided work on a research prioritization agenda, for which a Delphi exercise was performed and a manuscript drafted. A theoretical model framework was advanced, with three case studies selected for the population models to be developed. Relevant data were identified, collected, and evaluated. More than 100 database owners were contacted, and the infrastructure to gather and share the data publicly was implemented, with the legal process to complete data-sharing agreements ongoing.
During the third year, five papers were published based on the systematic reviews and research conducted for model development. Work on the case studies was concluded, with two chosen to be advanced in subsequent project activities. A second search for additional patient-level data was performed, and third parties can now apply for access to individual-level patient data on the ECRAID-Base EPI-Net platform: https://epi-net.eu/primavera/data-availability/(s’ouvre dans une nouvelle fenêtre). Work also began on cost-effectiveness analyses, as well as model evaluation and sustainability planning, with results expected to be reported over the following two years.
In the fourth year, two papers were published based on systematic reviews and model development research, and two additional manuscripts addressed future priorities for AMR research and challenges in data sharing. Efforts to gather anonymized individual-level patient data continued, resulting in the collection of 14,058 patient-level records from 19 of the 34 resistance–pathogen–infection groups, out of 196 eligible studies contacted. Three case studies—focusing on E. coli, S. aureus, and K. pneumoniae—were selected for programming language implementation and the development of a joint code repository. Work on cost-effectiveness analyses, model evaluation, and sustainability continued, with final results expected in the project’s last year.
To ensure continuous progress, the consortium held three annual meetings, four teleconferences with the SAC, and three workshops to advance model development. Dissemination activities included press releases and social media posts aligned with project milestones and outputs, which contributed to increasing project visibility and promoting the results to the broader scientific community.
The outcomes of the PrIMAVeRa project are expected to generate several major impacts:
I. Faster and more effective access to relevant data: the epidemiological repository will allow access to a publicly available, searchable database on the epidemiology of a range of common bacterial infections, their associated health burden, and resource consumption for a wide range of drug-resistant as well as drug-susceptible pathogens;
II. Better capability for real-time, data-driven decision-making by policymakers and healthcare managers on vaccine and mAb strategies by utilizing well-designed mathematical models available through a user-friendly interface with country-specific information for parametrisation;
III. An innovative evidence-based approach to prioritize research and development strategies to reduce the burden of relevant AMR through vaccines and mAbs. The combination of innovative decision tools and access to real-world data may guide and thus improve the economic return of R&D in the antibacterial field, making the development of novel, effective treatments more attainable and will help fight the emergence and spread of untreatable infections.
What differentiates PrIMAVeRa from other initiatives is that the project focuses on pathogen-infection-specific impact of AMR within different patient strata, trying to distinguish the impact of gender, age, frailty, and other important risk profiles to provide actionable data for prioritization of implementation of preventive strategies, like vaccines and mAbs.
I. Faster and more effective access to relevant data: the epidemiological repository will allow access to a publicly available, searchable database on the epidemiology of a range of common bacterial infections, their associated health burden, and resource consumption for a wide range of drug-resistant as well as drug-susceptible pathogens;
II. Better capability for real-time, data-driven decision-making by policymakers and healthcare managers on vaccine and mAb strategies by utilizing well-designed mathematical models available through a user-friendly interface with country-specific information for parametrisation;
III. An innovative evidence-based approach to prioritize research and development strategies to reduce the burden of relevant AMR through vaccines and mAbs. The combination of innovative decision tools and access to real-world data may guide and thus improve the economic return of R&D in the antibacterial field, making the development of novel, effective treatments more attainable and will help fight the emergence and spread of untreatable infections.
What differentiates PrIMAVeRa from other initiatives is that the project focuses on pathogen-infection-specific impact of AMR within different patient strata, trying to distinguish the impact of gender, age, frailty, and other important risk profiles to provide actionable data for prioritization of implementation of preventive strategies, like vaccines and mAbs.