In practice, our work within 3TR has been organised in 10 work packages (WP) with clearly defined objectives and responsibilities for each partner involved. Each work package is run by a dedicated work package leader , who is the “driver” of the specific WP activities and reports back to the Management team and Joint Steering Committee.
WP1: Data Management
Lead: Fundació Centre de Regulació Genòmico (CRG)
Data management is the backbone of the project: WP1 aims to build a centralised database that standardises all data generated and investigated by the different research teams within 3TR. Moreover, WP1 will help connect data to secondary analysis tools and annotations while also facilitating sustainability.
WP2: Quality Control & Ethics
Lead/Co-lead: European Respiratory Society (ERS) / Queen Mary University London (QMUL)
WP2 will closely monitor and safeguard that the clinical trials and studies envisaged within 3TR (incl. patient recruitment) will meet the highest quality control standards and ethical requirements. WP2 will deliver and regularly update a set of Standard Operation Procedures (SOPs) and templates to be used by the different 3TR teams for the set-up of central documents and quality control processes a their site. To this end, WP2 will also closely collaborate with the Ethical and Regulatory Advisory Board and seek the involvement of patient associations and charities.
WP3: Sample Logistics
The 3TR sample collection is of top priority. The main role of WP3 is thus to organise and centralise the storage and processing of any sample deemed worth profiling within the project. To this end, WP3 will set up an infrastructure for the procurement, registration, storage, processing and monitoring of biosamples adhering to strict quality control procedures. It will also ensure that ethical and privacy requirements and rules be met.
WP4: Profiling & Systems Biology / Data Integration Group
Lead: Fundación Pública Andaluza Progreso y Salud (FPS) / Pfizer
Running all data analyses and hosting the bioinformatics platform WP 4 is at the core of 3TR. Next to organising and profiling the samples from existing cohorts and the new prospective 3TR collection, the WP will identify and verify the molecular pathways of response and non-response to treatment and respective biomarkers. Moreover, WP4 will identify disease endotypes and develop predictive models of disease trajectories.
WP5: Cross-disease Activities
Lead/Co-Lead: Fondazione Irccs Ca’ Granda IRCCS (IRCCS) / Sanofi & Pfizer
WP5 is conceived as a central forum for the discussion and interpretation of results across the different diseases including a “Data Interpretation Group”. Additionally, WP5 will essentially provide the basis for the comparison of clinical, omic and bioinformatics data collected across the seven diseases by harmonising definitions, overseeing recruitment timings, monitoring the clinical data used in the prospective collection and aligning these data to outputs of the selected externally funded trials. WP5 will report back to the Joint Steering Committee proposing potential additional analyses and "sub-projects" within 3TR.
WP6: RA/SLE/MS (disease cluster)
Lead: University of Manchester
WP6 is one of the three so-called disease cluster WPs which are in charge of the patient recruitment, sample provision and determination of immune-mediated mechanisms of response or non-response to treatment strategies in the seven diseases. In this regard WP6 is responsible for the trials and analyses addressing RA, SLE and MS.
WP7: Inflammatory Bowel Disease (IBD) (disease cluster)
Lead: Christian-Albrechts-Universität zu Kiel
WP7 will provide access to and analyse retrospective longitudinal cohorts of IBD patients undergoing biologic therapy. Furthermore, the partners involved in this WP will conduct an observational open-label study with longitudinal biosamples on standard of care therapies. The ultimate objective is to determine the immune-mediated mechanisms of response or non-response to targeted therapies in IBDs and to develop validation assays in complex human cellular models.
WP8: COPD/Asthma (disease cluster)
Lead: University of Leicester
Representing respiratory diseases WP8 will catalogue retrospective studies, determine current and prospective observational and interventional trials to be aligned, and develop Pan-European pragmatic clinical trial platforms to support embedded experimental medicine studies. In addition, the WP will provide data and samples for the identification of predictors of response, biomarkers, and new therapeutic targets via a harmonised bioresource and knowledge management platform.
Lead: Fundación Pública Andaluza Progreso y Salud (FPS)
WP9 is in charge of the overall project management providing optimal guidance and support to all partners through a quick set-up of effective management and communication structures. It will ensure proper documentation of project activities and transparent communication between partners and the IMI. In addition, WP9 will be responsible for external outreach activities aiming to create visibility for 3TR and accelerating the uptake and exploitation of future results by reaching out to relevant stakeholders.
WP10: Engagement with Regulators
Lead: Takeda / Karolinska Institutet
The goals of 3TR might lead to biomarker signatures or possibly simplified single biological biomarkers that can be used as trial endpoints or enrich studies for responder populations to improve efficiency of clinical trials or aid precision medicine in the clinic. Against this backdrop, WP 10 will establish a biomarker and clinical endpoint group via patient organisations with stakeholder representation from patients, academia, professional societies and industry in alignment to similar consortia. Moreover, it will communicate and interact with relevant regulatory stakeholders to define the path for qualification of identified biomarkers.