Since the start of HT Advance, the project has progressed from trial preparation and infrastructure set up to active clinical recruitment, large scale multi omics data generation and advanced regulatory, methodological and translational activities.
During period 1, the main focus was the preparation and launch of the HT PREDICT randomised controlled trial, the preparation of the HT ENDO trial design, and the establishment of the technical and organisational infrastructure required for the project. Ethical approval for HT PREDICT was obtained for the Nijmegen site and recruitment started, with first patients completing the study by the end of the period. The HT ENDO trial design and methodology were finalised in close collaboration across the consortium, together with the initial statistical and methodological frameworks. A Multi Omics Data Management Platform (MODMAP) was developed and deployed, integrating sample tracking, an electronic case report form and a clinician interface for visualisation of machine learning based predictions. OMICS partners installed equipment, trained staff and validated protocols to ensure robust and reproducible measurements. In parallel, legal, ethical and regulatory documentation, including GDPR and the EU AI Act, was reviewed, and dissemination and project governance structures were put in place.
In period 2, ethical approval was obtained also for HT PREDICT for the Zurich site and recruitment is ongoing across sites. By the end of the second period nearly half of the patients planned had been recruited. Sample circulation across centres and OMICS laboratories has been fully implemented and validated, demonstrating reliable logistics, tracking and reporting pipelines, with early cross centre validation confirming strong reproducibility. Around 400 samples have already been analysed and uploaded to MODMAP. For HT ENDO, the trial design was optimised into a discordancy trial, and extensive technical, GSPR and IVDR documentation was prepared for regulatory submission. However, IVDR regulation still represent a challenge for this academic project.
Substantial methodological, statistical, legal and regulatory work underpinned the clinical activities, including the HT PREDICT interim analysis plan, the HT ENDO protocol, and the adaptation of health economic evaluation criteria to the trial designs. WP4 contributed through expert interviews to define the standard patient journey and by developing an outlay of a possible product roadmap for the MOMICS ENDO biomarker. Overall, the project has successfully transitioned from set up to integrated clinical, analytical and translational implementation.
