Periodic Reporting for period 1 - SCREEN4CARE (Shortening the path to rare disease diagnosis by using newborn genetic screening and digital technologies)
Okres sprawozdawczy: 2021-10-01 do 2022-09-30
There are over 7000 rare diseases resulting in 30 million Patients in Europe with a Rare Disease (RD) and globally 250 million Patients are affected. Being 75% of RDs of genetic origin, genetic diagnosis is compulsory patients can enter into an appropriate and often personalized path of care. Consequently, less than 10% of Person 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. The Screen4Care (S4C) project therefore aims at accelerating the diagnosis for RDs using a multi-tier strategy based on genetic newborn screening (gNBS) and digital technologies.
Although singularly rare, RDs are frequent in total, and represent an heavy burden for the society since they span across a plethora multisystemic syndromes, involving virtually every single organ or physiological function, and underlined by thousand different mutated genes. Consequently RDs profoundly affect PLWRD life and impact on society for the following main reasons:
• the diagnosis is often delayed and PLWRD experience a diagnostic odyssey (diagnostic effort dispersion)
• scientific knowledge about RDs remain poor
• social and psychological consequences are very important at any age
• Health care is often inadequate
• access to treatments and therapies is insufficient and scares
These major hurdles are exploited in delayed diagnosis of about 5-7 years, lack of Research & Development and lack of access to cure.
Although singularly rare, RDs are frequent in total, and represent an heavy burden for the society since they span across a plethora multisystemic syndromes, involving virtually every single organ or physiological function, and underlined by thousand different mutated genes. Consequently RDs profoundly affect PLWRD life and impact on society for the following main reasons:
• the diagnosis is often delayed and PLWRD experience a diagnostic odyssey (diagnostic effort dispersion)
• scientific knowledge about RDs remain poor
• social and psychological consequences are very important at any age
• Health care is often inadequate
• access to treatments and therapies is insufficient and scares
These major hurdles are exploited in delayed diagnosis of about 5-7 years, lack of Research & Development and lack of access to cure.
1-Identified existing resources by Horizon Scan.
First S4C objective is to identify existing resources and initiatives to be used as fundament knowledge to build up the project ecosystem. These resources include European-wide data sources amenable for Machine-learning (ML), regulatory frameworks, ethical, legal, and business considerations in the field of gNBS and digital technologies. Main results S4C has achieved for this objective are : i) analyses of regulatory environment for ML-based screening which will be used in work package (WP) 4 and 5, ii) definition of the framework of Data Protection Impact Assessment of ML-based screening technologies, for which we have provided legal recommendations for applying a pre-competitive business model, iii) definition of ethical principles and legal aspects of data sharing in S4C, including personal data and biospecimens, iv) identification of factors implicated in paying ML-based screening technologies and strategic recommendations provided.
2-Metadata repository: co-creation process
S4C main architectural concepts for the envisioned metadata repository and the first central modules of the S4C common data model were defined. Different S4C stakeholders were involved to identify potential co-creators and different processes have started. This task will start later in the project, but S4C has already established a transversal co-creation taskforce.
3-Genetic newborn screening (gNBS): defining RD selection criteria and strategies
S4C pillar gNBS process has started, and effort has been mainly put in identifying robust criteria to design the TREAT panel (treatable diseases). A robust process was set up and main criteria were established. These criteria are going to be validated using other gene sets, which were prioritized in other gNBS initiatives and scanning the Orphanet EU database. ACT panel (actionable diseases) design (chaired by Eurordis) has also started and WP3 is setting up modalities for the Barometer survey which will define the RD actionable criteria.
Ethical issues are outstanding in S4C, and we have created a WPs-transversal ELST (Ethical, Legal, and Societal Team) activity which was dedicated to the gNBS ethical applications at the clinical sites. Preference studies task to get an overview about gNBS perception by multiple stakeholder populations was set up, and ethical applications were already received or are pending. Also, gNBS costs related aspects have started and panel costs have been preliminary calculated.
4- Algorithms for Electronic Health Records scanning
Repurposing and adapting Electronic Health Records (EHR) algorithms work is ongoing, and during the first year the main work performed was on describing the new tool multi-spectral optoacoustic tomography (MSOT) for muscle imaging and deep phenotyping, which deliverable was achieved. Besides that, EHR activities are ongoing with intense collaboration with many partners.
5-Digital tools: toward meta-symptom- and symptom-checker
S4C digital task to empower Health Care Providers (HCPs) and patients to facilitate assessing of RD diagnosis based on a patients’ symptoms has started. To assess the benefit of the S4C Virtual Platform/App for healthcare and patients, an initial planning to liaise with and discuss the potential and benefit of the platform/app with both HCPs and patients was set up, and a dedicated meeting was scheduled to gather insights from all stakeholders and partners before mapping the first version of the platform schematic.
6-Project Coordination
Project management and coordination was carried on and has generated many results and deliverables. Firstly, the organisational structure of S4C has been realised and the Coordination-team (CT-Team) regularly meets on a weekly basis, as does the Executive Project Management Team (EPMT) by bi-monthly calls. Microsoft Teams is used is as the main data storage and communication platform for the Screen4Care project in the day-to-day management of the project. The External Ethics advisor was appointed and is monitoring the entire project ethical issues. Recommendations were included in first year report as Deliverable. The public project website, social media channels and a communication toolkit were created.
First S4C objective is to identify existing resources and initiatives to be used as fundament knowledge to build up the project ecosystem. These resources include European-wide data sources amenable for Machine-learning (ML), regulatory frameworks, ethical, legal, and business considerations in the field of gNBS and digital technologies. Main results S4C has achieved for this objective are : i) analyses of regulatory environment for ML-based screening which will be used in work package (WP) 4 and 5, ii) definition of the framework of Data Protection Impact Assessment of ML-based screening technologies, for which we have provided legal recommendations for applying a pre-competitive business model, iii) definition of ethical principles and legal aspects of data sharing in S4C, including personal data and biospecimens, iv) identification of factors implicated in paying ML-based screening technologies and strategic recommendations provided.
2-Metadata repository: co-creation process
S4C main architectural concepts for the envisioned metadata repository and the first central modules of the S4C common data model were defined. Different S4C stakeholders were involved to identify potential co-creators and different processes have started. This task will start later in the project, but S4C has already established a transversal co-creation taskforce.
3-Genetic newborn screening (gNBS): defining RD selection criteria and strategies
S4C pillar gNBS process has started, and effort has been mainly put in identifying robust criteria to design the TREAT panel (treatable diseases). A robust process was set up and main criteria were established. These criteria are going to be validated using other gene sets, which were prioritized in other gNBS initiatives and scanning the Orphanet EU database. ACT panel (actionable diseases) design (chaired by Eurordis) has also started and WP3 is setting up modalities for the Barometer survey which will define the RD actionable criteria.
Ethical issues are outstanding in S4C, and we have created a WPs-transversal ELST (Ethical, Legal, and Societal Team) activity which was dedicated to the gNBS ethical applications at the clinical sites. Preference studies task to get an overview about gNBS perception by multiple stakeholder populations was set up, and ethical applications were already received or are pending. Also, gNBS costs related aspects have started and panel costs have been preliminary calculated.
4- Algorithms for Electronic Health Records scanning
Repurposing and adapting Electronic Health Records (EHR) algorithms work is ongoing, and during the first year the main work performed was on describing the new tool multi-spectral optoacoustic tomography (MSOT) for muscle imaging and deep phenotyping, which deliverable was achieved. Besides that, EHR activities are ongoing with intense collaboration with many partners.
5-Digital tools: toward meta-symptom- and symptom-checker
S4C digital task to empower Health Care Providers (HCPs) and patients to facilitate assessing of RD diagnosis based on a patients’ symptoms has started. To assess the benefit of the S4C Virtual Platform/App for healthcare and patients, an initial planning to liaise with and discuss the potential and benefit of the platform/app with both HCPs and patients was set up, and a dedicated meeting was scheduled to gather insights from all stakeholders and partners before mapping the first version of the platform schematic.
6-Project Coordination
Project management and coordination was carried on and has generated many results and deliverables. Firstly, the organisational structure of S4C has been realised and the Coordination-team (CT-Team) regularly meets on a weekly basis, as does the Executive Project Management Team (EPMT) by bi-monthly calls. Microsoft Teams is used is as the main data storage and communication platform for the Screen4Care project in the day-to-day management of the project. The External Ethics advisor was appointed and is monitoring the entire project ethical issues. Recommendations were included in first year report as Deliverable. The public project website, social media channels and a communication toolkit were created.
Several progresses were made during the first year of the S4C project. We have established and consolidated the managing structure, which has allowed to carry on activities smoothly, to establish several outstanding collaborations, and to 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 panels designing were already considered and deeply discussed, landscape analysis of RD ecosystem was already started, as was federated metadata co-creation process, and HER algorithm development and virtual clinics planning are ongoing. Although preliminarily, NBS costs have been considered. Definition of the precise number of infants who will be screened by gNBS is ongoing. More results will be concretized during the next years, to bring solutions to the RD community, in order to get an early diagnosis and availability of an appropriate path of care.