In the first period of the project (May 2015-October 2016) the following work has been done:
Creation, development and maintenance of ENSAT-HT clinical data capture model including the development and roll out of a fully functional online registry supporting data capture, biomaterial transfer inventory and connection to the ENSAT registry. Consent from all collaborators on data sharing protocols has been achieved. A Research Data Management Database (RDMP) has been deployed and populated with sample data 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 realised. A systematic review of machine learning algorithms for omics dataset and study various prospective techniques has been undertaken. Different processing pipelines for omics data management have been supported. An investigation of publically available multi-omics datasets to study the impact of feature sub-selection on the classification accuracy of phenotypes has been undertaken.
Within work period 1, we have appointed all staff to key posts. A full inventory and selection of samples archived at study centres has been prepared in preparation for shipping. We have prepared and submitted all the necessary legal documentation to permit sample transfer. A study protocol for WP2 and WP3 has been produced and made available to the consortium members. All groups have commenced their technical validation and pilot studies and these are all on schedule. Some of these have resulted in the development of targeted sequencing kits which can be used to identify genotypes of endocrine hypertension and these will be commercially available. Standard operating procedures have been produced or are in progress and these are available on the consortium website. Publications acknowledging ENSAT-HT have also been produced.
Biosamples have been collected from over 235 samples of patients with PA, PPGL, CS, PHT and HV have been identified and analyses of plasma and urine catecholamines and steroids have been initiated. Targeted metabolomics profiling has been setup in different categories of patients with endocrine hypertension, showing good discriminant properties for further analyses. The studies on untargeted metalomics have been initiated using 1H-NMR spectroscopy and QTOF mass spectrometry. Pilot experiments have been successfully performed to determine optimal sampling conditions and preparations for both plasma and urine and to study the influence of different factors. Standard operating procedures for optimal sampling, labeling and sending instructions have been formalised and made available to the consortium.
At the end of the Period 1, all participants of WP4 have successfully appointed the appropriate personnel and have commenced to work on the clinical studies. All tasks are progressing well.
In the first instance, we have written the clinical protocol and have worked altogether to homogenize our standard operating procedures for the measurement of blood pressure, the screening for secondary hypertension the hormonal assessment. We also established all the criteria for the e-CRF in collaboration with WP1, WP2 and WP5. The list of items have been provided to WP1 for the ENSAT-HT registry.
Standard operating procedures have been written for the management of blood samples for the omics and for the hormonal assessment. In the second instance four centres have been working with their respective ethical boards to have the legal authorization to begin the first study for the validation of the omics. Four centres have submitted the protocol to their legal authorities and ethical approval was obtained in two centres. Until now 30 patients have been included in the study. The data of these patients have been entered in the ENSAT-HT registry.
We undertook a review of omics assessment methods used by the main HTA bodies - national public agencies, other public and private organizations -, 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. Twenty-five reports and articles have been finally taken into account regarding 17 MAAAs. 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.
In period 1 the priority was first to set up the classic communication tools for the project such as a logo representing the project, the website and a leaflet. A press release was published by the coordinator at the start of the project and send for dissemination/appropriation to all partners.
The missions of the Innovation Management Board that will be activated later in the project were presented at the kick-off meeting as well as an introduction by P13 to general Intellectual Property Issues in Research projects.
In period 1 the management tools and templates for the project for the scientific as well as for the financial monitoring of the project have been set up. The monitoring of the advances in the project has been started with regular updates to be delivered by the WP leaders. Two meetings with all partners have been organized during this period. Partners have been briefed at those meetings on the general H2020 rules and reporting procedures. Standard operating procedures for the ENSAT-HT study have been prepared and made available to the consortium.