WP1

Creation, development and maintenance of ENSAT-HT clinical data capture model and maintenance of online registry supporting data capture, biomaterial transfer inventory and connection to ENSAT registry have been done. Advanced functionality includes the development of pairing algorithm for secondary study and the bulk upload of extended retrospective clinical data.

A Research Data Management Platform (RDMP) has been deployed and populated with 7 omics datasets recently provided by collaborators along with its provenance. Procurement, installation and configuration of infrastructure and hardware, for hosting omics data within Safe Heaven environment have been completed.

The Automated Multi-omics Integrative Pipeline is developed and successfully deployed on the hardware. This pipeline accesses the ENSAT-HT omics datasets through RDMP Software. It is used for the extensive analysis of multiomics data under different scenarios. The best feature selection methods and machine learning algorithms for each scenario are finalised. Multiomics signatures were identified which provide high classification accuracies.

All partners have completed pilot studies, have characterised and validated their techniques and produced standard operating procedures.  Omics analysis of retrospective samples from all categories of patients has been completed.  Sample bias, data normalisation processes and missing data imputation procedures have been discussed extensively and implemented. A single-omics and multi-omics signature has now been generated by WP1. 

Work has been presented at national and international conferences and several high-impact factor publications have been produced.

Nearly 6000 blood and urine samples have been collected, circulated and analysed amongst the partners of WP3. Potential biomarkers for the distinction of primary and various types of endocrine hypertension have been identified using advanced measurement methods like mass-spectrometry and nuclear magnetic resonance (NMR). High classification accuracy has been achieved in single diagnostic methods. Combining catecholamine metabolites with plasma steroids obtained even better results than the single omics alone. This provides a promising outlook for the distinct combination of biomarkers that finally create the signature of biomarkers.

The clinical protocol has been written and all the criteria for the e-CRF have been established in collaboration with WP1, WP2 and WP5. Standard operating procedures for the management of blood samples for the omics assessment and hormonal assessment have been written. Four centers have started recruitment of patients for the clinical accuracy study during the first periods. Additional center have been identified to increase inclusion rates. During period 3, three new clinical centers have received ethical approval. Seven active centers are now including patients in the protocol. Recruitment rates have significantly increased over the last period.

A review of omics assessment methods used by the main HTA bodies - national public agencies, other public and private organizations – was undertaken, in order to identify the evidence required, in terms of criteria used and methods applied. Only multi-analyte assays with algorithmic analyses (MAAA), cancer and non-cancer, non-companion (stand-alone) tests that are actionable and have been evaluated by at least one HTA body until May 2016 were included. As assessment criteria, clinical validity and clinical utility were largely used, as well as economic, ethical, legal and social aspects. The two main models used were the EUnetHTA Core model or the ACCE framework, which could be adapted to the assessment of MAAAs. The work was validated with EUnetHTA.

The endpoint selection for the economic evaluation has been finalized. The economic evaluation will start once the clinical study will have been further advanced.

A project website was  created and regularly updated with photos, publications and results of the consortium. A graphic video on ENSAT-HT was produced and disseminated on the partners’ network.

ENSAT-HT initiated contact with the Corbel project that will try to assist the ENSAT-HT consortium in making contacts to industry /SMEs that potentially could be interested in cooperating on the exploitation of our results and identified biomakers.

WP 7 is monitoring  the progress of all the WPs, following the distribution of funds , organising the meetings of the consortium and ExCom and assisting partners individually on any administrative or legal and financial questions related to the EC rules.