WA-A: Tools
We have developed biorepositories of data that automates the capture of clinical, molecular, and imaging data and allows secure, effective exploration of aggregated multi-layer data by clinical investigators. It incorporates a user-friendly tool for the navigation and analysis of the data to facilitate the clinical decision making (WP2). In addition, we have developed and implemented two different tools to facilitate the clinical trial management. iTRACKER, a web-based Clinical Management System to optimize study workflows; iBANK, a virtual biorepository of data; and the elevated eCRF a digital system that goes beyond conventional data recording, integrating all the developed tools in the project to facilitate the analysis of multi-parameter data for clinical decision-making (WP3).
WA-B: Methods
We have continued in silico modelling of both novel adaptive, seamless clinical trial methods in a retrospective fashion and of circulating biomarkers. (WP8 and WP9). In addition, we have the approvals in place in two sites to start the RELEVANCE study (a real-world data basket validation trial) and the rest are in the process of obtaining the approval (WP10).We have also finalized the health economic evaluation that assesses effectiveness of the investigational treatment alongside the BoB trial as a use case. An online course summarizing the learnings and implications of the health economics activities, with a focus on estimating cost-effectiveness and budget impact using clinical data from innovative trials, is published on the project website (WP11).
WA-C: Biomarkers
We have established the repositories to manage the project data. Molecular data undergoes format harmonization and annotation via a local instance of the MTBP. We have also developed specifications on sample processing and shipping as well as the technical specifications for data processing and analysis for plasma proteomics and ctDNA (WP4). On the other hand, imaging biomarker validation utilizes a distributed image repository tool based on the JIP. Enhancements to the platform, specifically tailored for CCE_DART, include additional documentation sections to support the development of analytical methods and local platform operation (WP6). Real-world data and open-access datasets have been used for temporary training. We have validated the setup, showing potential for distributed deep learning tool development (WP4 and WP5). Moreover, progress has been made in refining AI-based methods for biomarker discovery in multi-omics data. Methods include explainable ML for complex gene interaction patterns and a transformer-based model for leveraging multi-centre datasets. A pipeline for enriching molecular signatures with external evidence has also been developed. Core technical contributions are completed, with validation and publication preparation ongoing (WP7).
WA-D: Patient
The sub-study to collect Patient Reported Outcomes (PRO) in clinical trials using the PROACT 2.0 tool is ready to start, and it operates independently from the BoB trial for broader patient recruitment (WP12). As for WP13, we have executed two workshops for researchers to promote patient participation in research activities (Participatory Research). In addition, we have developed and launched iENTER, a website mainly aimed at improving the informative process for patients who are potentially eligible to the BoB trial. Two other tools integrated with iENTER were developed within WP14: iCONSENT (web app to enhance the Informed Consent Process of patients going to decide about participating in the BoB trial; delivered during RP1 and iPARTICIPATE (web app with personalized access to BoB trial information and to communication tools for enrolled patients; delivered during RP2). Piloting of these WP13 and WP14 web tools will be performed during the next RP in the exploitation WP19.
WA-E: Dissemination
Dissemination activities have been carried out in accordance with the project communication plan (WP18). We have also defined and exploitation strategy for the project. Two KERs (iTRACKER and iENTER) have been analysed and one of them, iTRACKER, is on Business plan preparation. In addition, maintenance and the piloting of some studies is going on (WP19). Finally, we are organizing the second workshop with key stakeholders to develop a consensus around the application of new clinical trial methods in clinical drug development.
