Periodic Reporting for period 1 - EDENT1FI (European action for the Diagnosis of Early Non-clinical Type 1 diabetes For disease Interception)
Reporting period: 2023-11-01 to 2024-10-31
EDENT1FI aims to address the unmet need of a unified European strategy for screening for early stages of type 1 diabetes (T1D) in children from the general population. T1D is the most common metabolic/autoimmune disorder in children and has a lifelong impact on those affected and their families/caregivers. In Europe, 300 000 children and adolescents live with T1D and every year 15 per 100 000 European citizens receive a new diagnosis. The initial autoimmune reaction can be detected months or years in advance of symptoms, through the presence of autoantibodies (AABs) in the blood. Individuals with 2 or more of these biomarkers will develop clinical diabetes in their lifetime, creating an opportunity for early detection and intervention. Research shows that screening, education and follow-up of children with presymptomatic T1D lead to better glycemic control and less complications (e.g. diabetic ketoacidosis).
In this project, we aim to apply and evaluate an optimal general population screening strategy through detection of multiple AABs for identification of presymptomatic T1D stages in children, by assessing 200 000 children across Europe. During this screening, we will evaluate the feasibility and psychological/economic impact of screening strategies in different regions of Europe. In addition, we will examine novel approaches to refine estimates of progression rates to clinical disease. These stratification approaches will be transformed into innovative designs for clinical trials. Finally, we aim to communicate the project’s goal and results to diverse stakeholders, incl. children, patient advocates, public health experts, endocrinology specialists and other relevant healthcare providers, industry and regulatory bodies. Expected impacts and outcomes include early diagnosis of pre-clinical T1D, with guidance for follow-up, resulting in reduced disease severity at diagnosis; development and implementation of a roadmap for preventive and disease modifying therapies; increased availability of validated early disease progression biomarkers; and novel modeling tools focused on personalized risk monitoring and health interventions for end-users.
In this project, we aim to apply and evaluate an optimal general population screening strategy through detection of multiple AABs for identification of presymptomatic T1D stages in children, by assessing 200 000 children across Europe. During this screening, we will evaluate the feasibility and psychological/economic impact of screening strategies in different regions of Europe. In addition, we will examine novel approaches to refine estimates of progression rates to clinical disease. These stratification approaches will be transformed into innovative designs for clinical trials. Finally, we aim to communicate the project’s goal and results to diverse stakeholders, incl. children, patient advocates, public health experts, endocrinology specialists and other relevant healthcare providers, industry and regulatory bodies. Expected impacts and outcomes include early diagnosis of pre-clinical T1D, with guidance for follow-up, resulting in reduced disease severity at diagnosis; development and implementation of a roadmap for preventive and disease modifying therapies; increased availability of validated early disease progression biomarkers; and novel modeling tools focused on personalized risk monitoring and health interventions for end-users.
In the 1st year of EDENT1FI, a framework for AAB screening was provided to and approved by the Ethics Advisory board and implemented in the screening sites. We screened 25 012 children across 8 sites in Germany, Denmark/Sweden, UK, Italy, Czechia, Poland and Portugal in year 1, exceeding our expectations. An EDENT1FI monitoring protocol has been developed and is distributed for local adaptation and approval. EDENT1FI established its own ‘screening database’ with data from all participating children. In addition, we are working on an automated dataflow to the European Pre-T1D Registry, in which data of AAB positive children are collected.
To evaluate the feasibility of screening, questionnaires for parents and healthcare professionals (HCPs) have been developed, ethically assessed and are being implemented gradually at the screening sites. In addition, a systematic review on the psychological impact has been submitted for publication and a second systematic review on short- and long-term health economic impact of screening is in final stages of preparation.
To examine novel approaches to refine stratification and monitoring, a follow-up study protocol is being developed to determine minimally invasive methods to monitor the evolution of T1D, and to implement novel metabolic and glycemic approaches, including the use of continuous glucose monitoring (CGM), home oral glucose tolerance test (OGTT) and proinsulin/c-peptide monitoring.
To translate stratification approaches into innovative clinical trial designs for disease interception, we are developing a master protocol, which can serve as base protocol for other researchers and industry. In addition, extensive analysis of large datasets and existing literature is ongoing to explore improved outcome markers suitable for prediction of disease progression.
To promote communications to critical stakeholders, we are appointing a professional agency to support the communication campaign targeting all levels of stakeholders, with a particular focus on the general public. Communication to HCPs and the general public was initiated by: educating HCPs at international/local conferences, providing communications materials (brochures, leaflets, website), local language articles, and presence in media. In addition, our industry partners have started with broadscale international campaigns on awareness on screening. Finally, discussions with regulatory bodies (local, national and international) have been initiated, e.g. in the European Parliament.
To evaluate the feasibility of screening, questionnaires for parents and healthcare professionals (HCPs) have been developed, ethically assessed and are being implemented gradually at the screening sites. In addition, a systematic review on the psychological impact has been submitted for publication and a second systematic review on short- and long-term health economic impact of screening is in final stages of preparation.
To examine novel approaches to refine stratification and monitoring, a follow-up study protocol is being developed to determine minimally invasive methods to monitor the evolution of T1D, and to implement novel metabolic and glycemic approaches, including the use of continuous glucose monitoring (CGM), home oral glucose tolerance test (OGTT) and proinsulin/c-peptide monitoring.
To translate stratification approaches into innovative clinical trial designs for disease interception, we are developing a master protocol, which can serve as base protocol for other researchers and industry. In addition, extensive analysis of large datasets and existing literature is ongoing to explore improved outcome markers suitable for prediction of disease progression.
To promote communications to critical stakeholders, we are appointing a professional agency to support the communication campaign targeting all levels of stakeholders, with a particular focus on the general public. Communication to HCPs and the general public was initiated by: educating HCPs at international/local conferences, providing communications materials (brochures, leaflets, website), local language articles, and presence in media. In addition, our industry partners have started with broadscale international campaigns on awareness on screening. Finally, discussions with regulatory bodies (local, national and international) have been initiated, e.g. in the European Parliament.
EDENT1FI’s ambition is to achieve a paradigm shift in the way Europe is diagnosing T1D and move towards a systematic screening of the general population to detect those at early stages of T1D. In addition, we want to offer those with early-stage T1D more timely, personalized follow-up and interventions, through better information and education of all stakeholders. Based on the results of this project, we aim to roll out the first European roadmap for screening of the general population to diagnose early-stage T1D and make Europe the leader in the prevention of the disease. Therefore, we have to adjust the way the medical profession sees T1D and, through information campaigns, consensus papers and guidelines, irreversibly move the healthcare system towards diagnosing the early stages of T1D (before symptoms arise). To reach HCPs, we are currently present at international and local conferences (e.g. oral/poster presentations, booths) and succeeded in putting the topic of screening on the program of several of those international conferences (e.g. EASD, IDS). We are creating awareness on T1D screening by publishing articles in (local) magazines and journals for primary care physicians (e.g. in the Lancet Diabetes & Endocrinology, Médicine des Maladies Métaboliques, Science). A consensus on monitoring individuals with AAB-positive early-stage 3 T1D has been published, developed by EDENT1FI partners and external stakeholders. Following the publication of the monitoring guidelines, a consensus on screening for early T1D is now in progress, led by EDENT1FI partners. Finally, we aim to design novel clinical trial designs that consider the range of presymptomatic T1D stages, providing a fundamental framework for other researchers and industry.
In summary, EDENT1FI has hit the ground running with major impact already through its work and communication strategy in Europe and worldwide. We are sharing materials worldwide to initiatives that want to start screening for early stage T1D. In the EU, EDENT1FI has succeeded already in year 1 to put screening for early stage T1D on the political map.
In summary, EDENT1FI has hit the ground running with major impact already through its work and communication strategy in Europe and worldwide. We are sharing materials worldwide to initiatives that want to start screening for early stage T1D. In the EU, EDENT1FI has succeeded already in year 1 to put screening for early stage T1D on the political map.