COST Association, Avenue du Boulevard – Bolwerklaan 21, Belgium, 1210 Brussels
Cliniques Universitaires Saint-Luc, Université Catholique de Louvain 10 avenue Hippocrate Belgium 1200 Brussels
Mostar University Hospital, Bijeli Brijeg bb, Bosnia & Herzegovina 88000, Mostar
University Hospital of Endocrinology, Medical University, Sofia, Zdrave 2, Bulgaria 1431, Sofia
Education Centre For Sustainable Growth, Pibergårdsvej 9, Denmark 4040, Jyllinge
Med. Klinik IV, Klinikum der Universität München, LMU München, Ziemssenstraße 1, Germany, 80336, Munich
Semmelweis University, Koranyi Sandor str. 2/a, Hungary 1083 Budapest
University Hospital San Luigi Gonzaga, Regione Gonzole 10 Italy 10043, Orbassano
Lithuanian University of Health Sciences, Eiveniu str. 4 Lithuania 50161, Kaunas
University of Malta Medical School, Mater Dei Hospital, Department of Medicine, Division of Endocrinology, Mater Dei Hospital, Block A, Level O, Bkara Bypass, Malta, MSD2090, Msida
Radboud University Medical Centre, PO Box 9101, Netherlands 6500HB, Nijmegen
Diabetes and Metabolic Diseases, University Clinic of Endocrinology, 1000 Skopje, North Macedonia, Mother Teresa 17, Skopje 1000, North Macedonia 1000, Skopoje
ICBAS- University of Porto, Rua Jorge Viterbo Ferreira, n.228, Portugal, 4050-313, Porto
Carol Davila” University of Medicine and Pharmacy, 34-38 Aviatorilor Blvd, Romanian Psychoneuroendocrine Society, Romania, 011863, Bucharest
Grigore T. Popa University of Medicine and Pharmacy 16, Universitatii street, Romania 700115, Iasi
Clinic for Endocrinology, Diabetes and Metabolic Diseases, Faculty of Medicine, University of Belgrade, Dr Subotica 13, Serbia 11000, Belgrade
Uppsala Universitet, Akademiska sjukhuset, ing40, Sweden 75185, Uppsala
Canakkale Onsekiz Mart University Faculty of Medicine, Çanakkale, Turkey 17110, Çanakkale
Dokuz Eylul University, School of Medicine, Dokuz Eylul Universitesi Tip Fakultesi, Endokrinoloji Bilim Dali, Poliklinik Binasi Kat 1, Turkey 35340, Izmir
WG1: Harmonizing adrenal tumour clinical practice
Aim: to improve the standard of clinical practice, specifically targeting ITCs. This WG will be composed of adrenal tumour experts who will help disseminate state-of-the-art practices on adrenal tumour management through masterclasses. A first step will be to advertise this training effort in clinical structures throughout Europe, especially in ITCs, to maximise the knowledge dissemination among as many clinicians as possible. Clinicians wishing to attend the masterclasses will be identified. The Action will propose masterclasses covering the entire clinical spectrum of adrenal tumours, both in person (at the time of the yearly Action meetings), and using online virtual classrooms. ECIs will be targeted and prioritised. In addition to the masterclasses, adrenal tumour experts will also create consensus statements, methodological strategies including common diagnostic algorithms, and best-practice clinical guidelines for managing adrenal tumours, which will be endorsed by national, European and international professional and specialist societies and patient associations.
WG2. Harmonizing adrenal tumour research and -omics practice:
AIM: this WG will mainly focus on training researchers on modern research techniques relevant to the field of adrenal tumours, and to the perspective of next generation trials. We will organise masterclasses specifically targeting ITCs and young researchers. A dedicated theme will be generating and managing “omic” data (genomic, metabolomic, proteomic, radiomic) on adrenal tumours, with the aim of helping to implement molecular biomarkers. The Action will run master classes twice a year, either in person (at the time of the yearly meeting) or using online virtual. A second activity will be to identify and analyse state-of-the-art tools and technologies available in the more advanced groups, and make these available to groups with less experience and resources, again prioritising ITCs to help provide access to and training on such tool). A prototypical example is the genomic screening of 20 genes in pheochromocytoma, which is currently not available to some of the partners, but is routinely used by many of those located in COST countries. Ultimately, this will enable all centers to access the most advanced technologies. A third action of this WG will be to establish standard operating procedures (SOPs) for translational research, which each centre should follow to develop a biobank devoted to adrenal tumours These SOPs will guarantee the standardisation and quality of clinical data, biological material, and genomic analyses in agreement with all partners, and will be both feasible in all centres, as well as compatible with the best practices. This will be a prerequisite for future federated research including these centres. A final activity of this WG will be to coordinate the identification of two to three research questions that could be addressed by a randomised trial. This selection of the most relevant questions to address in priority will involve researchers and clinicians, but also patients’ representatives. Such trials would be the first step towards a new generation research framework, based on a common registry and AI, which is the end goal of HARMONISATION. The Action will apply for a separate funding to this end.
WG3. Harmonizing Information Technology / Artificial Intelligence tools towards a standardized registry:
AIM: the core of this WG is an expert IT/AI research team, specialised in implementing data warehouse solutions from unstructured medical records, using natural language processing (NLP) among other AI resources. This core team will provide a first generic solution for collecting a limited range of relevant clinical and biological data, feeding a registry dedicated to patient selections for trials on adrenal tumours. This solution will respect anonymization and legal obligations related to handling such data. The originality is that this will be the semi-automated data collection. For each patient included in this registry (after obtaining ethics approval and patient consent), clinicians will provide the unstructured medical record locally to the computing solution, which will anonymize and automatically and instantly extract the relevant data. The clinician will validate the accuracy of these data. A second task of this core expert group will be to spread the identified solution to the other centres for further testing, through exchange with local IT/AI experts (short term scientific missions) and by producing a Standard Operating Procedure. Local adaptation is mandatory in each centre. For instance, NLP adaptation to each language will be required. Local adaptations of this solution will then emerge, generating local registries. A third task will be the anonymized connection of all local registries to a centralized federal system (data will not be imported but will remain local and be interrogated in their respective centres) through coordinated exchange between IT specialists. This step will require specific authorization, which will be addressed in WG4. Finally, towards the end of this Action, in the perspective of launching a first trial, the Action will design and implement a series of optimized variables necessary for running the trial (randomization, then running the trial). This will be performed through a networking activity that will also involve clinicians and researchers. This Action will cover the networking activities (interdisciplinary exchanges between IT, clinicians and researchers, and connections between IT experts), while alternative funding will serve to implement computing solutions.
WG4. Harmonizing the ethical and legal framework towards the advent of federated European trials:
AIM: to help all centres get local clearance from ethics committees, and from any other regulatory body, to implement its local registry based on semi-automated treatment of medical records. The core team is composed of an academic, as well as a citizen science figure who is already deeply involved in the legal and ethical aspects at the national level of one of the participating countries. After analysing common areas of complexity, the first activity will be to create an initial document addressed to the ethical committee of one of the participating centres, allowing us to start the project. This document will emerge from the networking of this core actor with clinicians and researchers specialized in adrenal tumours. The second activity will be to adapt this document for each centre in each country. Significant networking activity will be needed between the core actor and the ethics/legal representatives of each centre. The third activity, at the end of this Action, will be to advocate towards the European Commission the establishment of a federated tool for interrogating all local registries in different countries. This Action will be part of a broader advocacy action to promote European standards for clinical databases and software approval. This WG will also have to include ethical stakeholders involved by the initiative. We will especially promote the principle of “Human Guarantee of AI”, which consists of applying regulatory principles immediately upstream and downstream of the AI algorithm itself, through points of human supervision. The goal is to ensure that algorithms adhere to standards of medical effectiveness and ethical responsibility. This key ethical feature is currently under discussion at the WHO
WG5. Communication, dissemination, and inclusiveness:
AIM: to involve new stakeholders and to disseminate the achievements of the Action to ensure uptake in the broader community. This WG will involve clinicians and scientists working on adrenal tumours, who will assign a specific liaison officer to actively promote the inclusion of new researchers and other reference networks, as well as communication professionals. These partners will develop a dedicated HARMONISATION website, coordinate and publish the WG’s results, translate scientific efforts into public dissemination, and also help coordinate and promote research proposals to fund future collaborative research promoted by this COST Action.