Creation, development and maintenance of ENSAT-HT clinical data capture model. Creation and maintenance of online registry supporting data capture, biomaterial transfer inventory and connection to ENSAT registry. Main work in this period is the further development of and output of monitoring report of eCRFs, as well as continuous linkage between ENSAT-HT and ENSAT.

The Automated Multi-omics Integrative Pipeline was developed and successfully deployed on the hardware. It is used for the extensive machine learning based analysis of multiomics data under different scenarios. The first identified multiomics signature and related classification accuracies were shared with collaborators.

A patent application is currently being drafted for the final multiomics signature. Also multiomics and monomics manuscripts are drafted and circulated amongst collaborators for their feedback.

Within period 4, WP2 has made significant progress.  Omics analysis of the retrospective samples has been completed.  Complex data normalisation processes and missing data imputation procedures have been implemented.  Using this expansive data set, a single-omics and multi-omics signature for each disease has been generated by WP1 which will be tested in the prospective study in WP4.  Samples from WP4 have been processed and circulated and OMICs measurements have commenced.

There have been a number of highly productive scientific exchanges within WP2, including visits to partner laboratories.  Work has been presented at several national and international conferences and several high-impact factor publications acknowledging ENSAT-HT have been produced. Discussion with intellectual property  officers regarding the single omics and multi-omics signature is ongoing. 

Samples from the prospective study in WP4 have been received by all centers. Measurement and analysis of plasma metanephrine, normetanephrine and 19 adrenal steroids have started and are predicted to be completed by September 2020. Measurement of urinary steroids on samples from the retrospective cohort have been run at UOB by a newly developed high throughput LC-MS/MS method to quantify 27 adrenal steroids. The method has been re-validated on a new mass spectrometer in anticipation of the measurements to perform for the prospective cohort. Plasma and urine samples were collected and analyzed by NMR spectroscopy and the spectral processing pipeline was further developed and validated for the prospective study.

In WP4, the clinical work package, recruitment of patients for a prospective accuracy study took off with the establishment of a clinical protocol, which was submitted and approved in all participating centers. Patient recruitment initially lagged behind, but with the inclusion of additional centers, currently more than 2200 patients have been included. A new statistical plan has been developed to determine the accuracy of the omics signature in diagnosing endocrine forms of hypertension. 

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.

A cross country comparison of current workup strategies for endocrine hypertension and costs of the current workups for patients with endocrine hypertension have been initiated in period 4.

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.

In period 4 of ENSAT-HT the main activity for WP6 was the preparation of the patent filing of the biomarker signature and the different discussions for future uptake/exploitation of this signature and the efforts for finding and industrial partners for its uptake. The twitter account of ENSAT-HT has been updated regularly throughout the period.

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.

By the end of the period 4 the project was hit by the COVID-19 restrictions that caused significate delay in the general work plan.