Periodic Reporting for period 2 - SCREEN4CARE (Shortening the path to rare disease diagnosis by using newborn genetic screening and digital technologies)
Okres sprawozdawczy: 2022-10-01 do 2023-09-30
There are over 7000 rare diseases, resulting in 30 million Patients in Europe with Rare Diseases (RD), and globally, 250 million Patients are affected. Being 75% of Rare Diseases (RDs) of genetic origin, genetic diagnosis is compulsory so patients can enter into an appropriate and often personalised path of care. Consequently, less than 10% of persons living With a Rare Disease (PLWRD) receive treatment, and only 1% are managed using an approved treatment in Europe. Achieving early diagnosis and delivering effective treatments for PLWRD, where the prevalence is low, have been described as one of the major global health challenges for the 21st century. Screen4Care (S4C) project aims to accelerate the diagnosis of RDs using a multi-tier strategy based on genetic newborn screening (gNBS) and digital technologies.
WP1 aims to create a common understanding of the business and regulatory framework for rare disease screening in Europe and has several tasks. Activities to analyse and scan rare disease (RD) initiatives and pre-existing RD resources, registries, and databases in Europe have been concluded. A comprehensive overview of available symptom checkers and related platforms was also finalised. The regulatory environment for ML-based screening technologies was defined, and regulatory guidance was developed. Notably, the Data Protection Impact Assessment Framework (DPIAF) of ML-based screening technologies was also described, legal recommendations for a pre-competitive business model were made, and the DPIAF and the pre-competitive business model have allowed to develop a code of ethical practice (CoEP) that has enabled sharing and access to personal data and biospecimen within the Screen4Care project while adhering to ethical principles and legal premises. WP1 has also produced recommendations for a pre-competitive business model. Work related to scrutinising the results of Screen4Care and disseminating key messages to patients, international screening societies, and other relevant organisations has started. It is ongoing via the Newborn Screening Forum (NBS Forum Chaired by Eurordis).
WP1activities to analyse and scan rare disease (RD) initiatives and pre-existing RD resources, registries, and databases in Europe have been concluded. A comprehensive overview of available symptom checkers and related platforms was also finalised. The regulatory environment for ML-based screening technologies was defined, and regulatory guidance was developed. Notably, the Data Protection Impact Assessment Framework (DPIAF) of ML-based screening technologies was also described, legal recommendations for a pre-competitive business model were made, and the DPIAF and the pre-competitive business model have allowed to develop a code of ethical practice (CoEP) that has enabled sharing and access to personal data and biospecimen within the Screen4Care project while adhering to ethical principles and legal premises. WP1 has also produced recommendations for a pre-competitive business model.
WP2 aims at establishing a federated infrastructure dedicated to rare disease data by descriptive metadata from data sites which go to federated metadata repository (MDR). WP2 also adapts federated machine learning algorithms to process data related to RDs. During the 2nd year the architectural details have been fully implemented, leading to the minimal viable product already in use. WP2 completed the development of the first central modules of the S4C standard data model (CDM) for enhancing patient documentation with neuromuscular disorders (WP4 and WP5). More than 180 potential co-researchers with experiential knowledge in this field's technical, ethical and legal aspects were engaged in 44 in-depth follow-up interviews to lead co-creation process to integrate a federated metadata infrastructure and digital tools.
WP3 finalized ethical approvals for the preference studies in Germany and Italy, so first focus group in Germany and Italy has started. The TREAT panel including 245 genes was finalized and designed. The ethical application for TREAT and WGS studies was approved in Italy, and is being prepared in Germany and France. The selection process for the ACT panel has been started, and a starting list for actionable rare diseases is available. The pipeline for data analysis, newborn recruitment and genetic output analysis was also fully defined.
WP4, whose main tasks include developing existing algorithms trained on EHRs and registries to identify and screen for undiagnosed patients in RDs, performing three pilots to validate the algorithms and test implementation in clinical practice, evaluating the feasibility and acceptance by patients and their families, HCPs and other stakeholders of the RD detection via HER; and formulating recommendations for public health authorities based on pilots’ outcomes, during the period also engaged in many activities of WP1 and WP2. WP4 partner Sanofi has conducted a thorough internal and external landscape assessment to identify existing algorithms (machine learning and knowledge-based), gather and systematise learning, evaluate external vendors, and assess implementation feasibility.
WP5 continued the planned engagement of the team with the patient advocacy community to identify phenotypes, refined metrics and designed the “symptom checker” app. UCD presented the app/virtual environment plans in focus groups with Eurordis and patient advisory/advocacy panels and revised the app in development in iterative design sprints, taking the tool into a working demonstrator from which a prototype can be produced. Several distinct parts of the app were developed in response to patient and stakeholder and ERNs’ suggestions so that the app/virtual environment in progress addresses the specific needs of these stakeholder groups, including kinaesthetic/touchscreen interfaces as well as text and visual interfaces, and two different output models.
Project management, communication and dissemination activities are carried out by WP 5 team according to the approved DoA.
WP1activities to analyse and scan rare disease (RD) initiatives and pre-existing RD resources, registries, and databases in Europe have been concluded. A comprehensive overview of available symptom checkers and related platforms was also finalised. The regulatory environment for ML-based screening technologies was defined, and regulatory guidance was developed. Notably, the Data Protection Impact Assessment Framework (DPIAF) of ML-based screening technologies was also described, legal recommendations for a pre-competitive business model were made, and the DPIAF and the pre-competitive business model have allowed to develop a code of ethical practice (CoEP) that has enabled sharing and access to personal data and biospecimen within the Screen4Care project while adhering to ethical principles and legal premises. WP1 has also produced recommendations for a pre-competitive business model.
WP2 aims at establishing a federated infrastructure dedicated to rare disease data by descriptive metadata from data sites which go to federated metadata repository (MDR). WP2 also adapts federated machine learning algorithms to process data related to RDs. During the 2nd year the architectural details have been fully implemented, leading to the minimal viable product already in use. WP2 completed the development of the first central modules of the S4C standard data model (CDM) for enhancing patient documentation with neuromuscular disorders (WP4 and WP5). More than 180 potential co-researchers with experiential knowledge in this field's technical, ethical and legal aspects were engaged in 44 in-depth follow-up interviews to lead co-creation process to integrate a federated metadata infrastructure and digital tools.
WP3 finalized ethical approvals for the preference studies in Germany and Italy, so first focus group in Germany and Italy has started. The TREAT panel including 245 genes was finalized and designed. The ethical application for TREAT and WGS studies was approved in Italy, and is being prepared in Germany and France. The selection process for the ACT panel has been started, and a starting list for actionable rare diseases is available. The pipeline for data analysis, newborn recruitment and genetic output analysis was also fully defined.
WP4, whose main tasks include developing existing algorithms trained on EHRs and registries to identify and screen for undiagnosed patients in RDs, performing three pilots to validate the algorithms and test implementation in clinical practice, evaluating the feasibility and acceptance by patients and their families, HCPs and other stakeholders of the RD detection via HER; and formulating recommendations for public health authorities based on pilots’ outcomes, during the period also engaged in many activities of WP1 and WP2. WP4 partner Sanofi has conducted a thorough internal and external landscape assessment to identify existing algorithms (machine learning and knowledge-based), gather and systematise learning, evaluate external vendors, and assess implementation feasibility.
WP5 continued the planned engagement of the team with the patient advocacy community to identify phenotypes, refined metrics and designed the “symptom checker” app. UCD presented the app/virtual environment plans in focus groups with Eurordis and patient advisory/advocacy panels and revised the app in development in iterative design sprints, taking the tool into a working demonstrator from which a prototype can be produced. Several distinct parts of the app were developed in response to patient and stakeholder and ERNs’ suggestions so that the app/virtual environment in progress addresses the specific needs of these stakeholder groups, including kinaesthetic/touchscreen interfaces as well as text and visual interfaces, and two different output models.
Project management, communication and dissemination activities are carried out by WP 5 team according to the approved DoA.
Several progresses were made during the 2nd year of the S4C project. We have completed activities, established and further consolidated the managing structure of Novel outstanding international collaborations within RD and newborn screening, and spread S4C knowledge worldwide. The important documents on data communication, management, and sharing were delivered as operational tasks of the project. Ethical issues and gene panel designing were completed for the TREAT panel, WGs, and preference studies. Landscape analysis of the RD ecosystem was also completed, a federated metadata co-creation process was defined, and tasks have started; HER algorithm development and virtual clinic planning are still under development. Although preliminarily, NBS costs have been considered. The definition of the precise number of infants who gNBS will screen is ongoing. More results will be concretised during the following years to bring solutions to the RD community to get an early diagnosis and availability of an appropriate care path.