Work Packages

PERFORM’s implementation is structured around 12 individual Work-Packages.

Led by a Work-Package leader, these will guide the project’s progress from its early “Discovery and Evaluation” phase where most of the clinical recruitment will be taking place, towards the “Validation and Implementation” stages, where data will be processed, treated and “translated” in order to be clinically and medically implemented.

Below you can find an overview of the individual Work-Packages, their objectives and the lead institution responsible for its implementation.

Work Package 1

Clinical Network and Biobanking

WP1 will be responsible for creating the PERFORM International Clinical Network (PERFORM-ICN), by combining the clinical data and sample banks from previous EU-funded studies undertaken by members of the consortium and effectively creating the most comprehensive and well-characterised biobank in Europe.

All clinical samples for the subsequent Work-Packages will be collected through WP1, including the diagnostic, genomic and proteomic studies to be conducted for Work-Packages 2-4.

WP1 is led by SERGAS – Servizo Galego de Saude, from Spain.

Work Package 2

Diagnostics

WP2 will provide high-throughput molecular diagnostics, enabling accurate patient assignment to bacterial or viral diagnostic categories and will validate candidate protein biomarkers to distinguish between bacterial and viral infection using immunoassays.

WP2 is led by the AMC – Academish Medisch Centrum bij de Universiteit van Amesterdam, in the Netherlands.

Work Package 3

Genomics

WP3’s main goal will be to provide detailed transcriptome profiling of febrile patients with bacterial or viral infections, in order to identify reliable genomic markers so as to improve diagnosis and clinical management. In order to so successfully, WP3 will need to:

1.Obtain a genome-wide transcriptomic profile by deep sequencing a subset of febrile individuals with confirmed diagnosis of bacterial or viral infections using samples from WP1;

2.Perform RNA expression studies in larger cohorts of febrile patients combining those with and without definitive diagnosis of infection, using samples from WP1;

3.Validate significantly differentially expressed genes, potential genomic markers identified on transcriptome studies by alternative methods, namely nanostring and qPCR.

WP3 is led by LSHTM – London School of Hygiene and Tropical Medicine.

Work Package 4

Proteomics

WP4 is responsible for identifying and selecting relevant and measurable sets of protein biomarkers, based on the proteomic profiling studies undertaken for the discovery cohorts that distinguish between bacterial and viral infections, as well as the subsequent validation of said candidate biomarkers.

Data integration will then allow for the design composition of the optimal protein biomarker panel capable of distinguishing between bacterial and viral infections.

WP4 will be led by RUMC – Stichting Katholieke Universiteit in the Netherlands.

Work Package 5

Comparative Health Care analysis and cost-effectiveness

WP5’s overarching aim will be the development of a robust decision analytic framework capable of modelling the relative costs, risks and benefits of introducing PERFORM’s new approach to diagnose and manage febrile children across different European health care settings. This framework will be informed by data collated from the other Work-Packages (primarily WP1) but also through healthcare provider and patient surveys.

In order to effectively measure the impact and costs of the new diagnostic approach, WP5’s model framework will take into account a detailed description of current pathways, practices and associated costs across the various existing health care models, at the European level.

WP5 will be led by LSHTM – London School of Hygiene and Tropical Medicine in the UK.

Work Package 6

Data Analysis and Modelling

WP6’s main role will be to analyse and integrate the clinical, transcriptomic and proteomic data to construct biomarker signatures able to distinguish between bacterial and viral infections. The focus will be on developing signatures that use the minimal number of biomarkers showing optimal sensitivity and specificity.

Additionally, WP6 will provide inputs and liaise closely with WP4 and 5 in order to contribute to their analysis work and undertake modelling of different management strategies for febrile children.

WP6 will be led by Imperial College in the UK.

Work Package 7

Model Implementation

WP7 will be responsible for receiving all transcriptomic and proteomic data from the patient cohorts and model the potential health-care costs that would be achieved through the widespread inclusion of the new diagnostic approach. A clinical management algorithm will be developed, encompassing the use of novel transcriptomic diagnostic tests and clinical markers.

WP7 will then evaluate the performance of the algorithm using modelling data obtained from the patient cohorts including sensitivity and specificity of the combination of clinical signs, symptoms and diagnostic tests, effectively integrating the findings and results from WPs 3-6 into base management guidelines.

WP7 will be led by Imperial College in the UK.

Work Package 8

Translation of biomarkers into prototype for validation

WP8 will evaluate different platforms and approaches for developing clinically applicable tests based on the transcriptomic and proteomic biomarker, facilitating future production of a rapid point of care test. The technological choices (ie molecular biology and/or immunoassay) will depend on the type and the number of biomarkers identified in the discovery study, along with sensitivity, specificity and potential for translation

WP8 will be led by Biomerieux in France.

Work Package 9

Clinical Translation

WP9 will closely evaluate the performance of the developed predictive models of bacterial or viral infection, through close interactions with WPs 5-8, developing necessary guidelines for future application in different European health-care settings.

Data and contacts established through WP10, particularly regarding project stakeholders will also factor in the development of new management guidelines for febrile children, taking into account the different national settings and health-care models.

WP9 will be led by Imperial College, in the UK.

Work Package 10

Dissemination and Stakeholder Engagement

WP10 will focus on establishing PERFORM’s communication strategy and activities, in such a way as to maximise the project’s reach and potential impact across its various stakeholder communities.

It will ensure results and outcomes are properly advertised and reach both international and national audiences, when relevant.

The WP will also look to maintain the project’s website up to date with the latest information and materials developed in the scope of the project.

WP10 will be led by Imperial College in the UK.

Work Package 11

Data Management

WP11’s main responsibility will be to ensure that the informatics needs of the project are adequately met, given the large number of patients involved as well as the large volume and variety of data that will be generated and collected across the different Work-Packages.

WP11 will set up the necessary underlying infrastructure and expertise for managing this data and supporting the subsequent informatics analysis carried out by the different Work-Packages. It will, furthermore, ensure continuous and reliable access to the data through a centralised and secure infrastructure housing the different data systems, on a data management repository.

WP11 will be led by Imperial College in the UK.

Work Package 12

Project Management

WP12 will ensure the efficient and effective management of the entire project, across its 5 year duration. The project coordinator will make sure that consortium partners are performing in accordance to the agreed Work-Plan, communicating with the European Commission on a periodic basis to provide relevant updates on the project’s performance.

Through WP12, it is intended that PERFORM runs smoothly and efficiently, so as maximise its expected outputs across the participating partner organisations.

WP12 will be led by Imperial College in the UK.