Periodic Reporting for period 1 - AD-RIDDLE (REAL-WORLD IMPLEMENTATION, DEPLOYMENT AND VALIDATION OF EARLY DETECTION TOOLS AND LIFESTYLE ENHANCEMENT)
Reporting period: 2024-01-01 to 2024-12-31
Alzheimer's disease (AD), the main cause of dementia, is one of the major global health challenges. With 67 million people at risk for AD dementia (prodromal and preclinical AD) in Europe, it's s a major unmet public health need. Yet, prevention and early detection strategies have been lacking. Recent advances in disease-modifying therapies and potential benefits of preventive multidomain interventions based on modifiable lifestyle and vascular factors (prevention potential ~40%) provide new opportunities. New developments in blood-based biomarkers (BBMs) and digital cognitive assessments (DCAs) enable broader, cost-effective testing. AD-RIDDLE explores toolbox platform concept, providing validated tools at each key step to enable health care systems and practitioners to deploy enhanced AD management across patient populations. The AD-RIDDLE toolbox platform will include; community outreach tools to increase awareness/activation; combination of clinically validated biomarkers: DCAs and BBMs, for early detection of AD dementia risk; validated algorithms supporting clinical decisions, to identify people who can benefit from preventive therapies (pharma/non-pharma) using precision prevention approach. The toolbox usability and efficacy will be tested in real-world settings. We expect that the AD-RIDDLE modular design can facilitate broad uptake from different healthcare systems, and its tools can advance research to develop cost-effective preventive therapies for AD, with scalability for other dementias.
We have started developing a modular digital engagement platform for public use, with input from key stakeholders in the ecosystem (e.g. researchers, healthcare providers, and advocacy organizations). Public involvement, awareness and outreach activities have also been initiated.
A 2-stage approach is being used to test and validate Digital Cognitive Assessments and Blood Based Biomarkers, starting with a pilot stage focused on assessing the feasibility and usability of DCAs, and continuing with larger-scale testing of both DCAs and BBMs, in alignment with implementation evaluation work. The protocol for the pilot stage and the BBMs protocol have been completed. In addition, the framework for the large-scale testing stage of both DCAs and BBMs has been laid out, aligning across all relevant work packages. We have also established the implementation evaluation framework including harmonization of variables and establishing the Community of Practice (CoP) process model and governance structure, including framework for documentation and sharing of implementation learnings.
The first version of the Data Map for existing data has been completed, and we have created an initial Data Flow overview that tracks how data at this stage of the project is currently being collected, shared, and managed. Development and/or testing of predictive algorithms/models was conducted in parallel in existing observational cohorts (early risk and disease detection) and multidomain lifestyle-based intervention RCTs (response to intervention).
To ensure the quality of the AD-RIDDLE toolbox and to provide ethical guidance on potential socio-ethical implications of the project, a review of relevant literature was conducted to explore the ethical concerns linked to the development and implementation of population-level health screening approaches for AD/dementia risk. In combination with the Public Involvement work and a policy and practice review, the findings will inform the AD-RIDDLE toolbox design.
A scoping review of funding models was conducted, with emphasis on health impact bonds in health intervention programs. A health economic model for dementia prevention has also been developed by integrating the effects of cardiovascular disease.
Furthermore, we have conducted an assessment of health technology assessment (HTA) evidence requirements across Europe relevant for the AD-RIDDLE toolbox development, and a HTA Standing Forum was set up.
Work has begun on the sustainability workstream to identify, prioritise and select the project assets in advance, with the aim of maximising the sustainability of AD-RIDDLE and its impact on the field.
A 2-stage approach is being used to test and validate Digital Cognitive Assessments and Blood Based Biomarkers, starting with a pilot stage focused on assessing the feasibility and usability of DCAs, and continuing with larger-scale testing of both DCAs and BBMs, in alignment with implementation evaluation work. The protocol for the pilot stage and the BBMs protocol have been completed. In addition, the framework for the large-scale testing stage of both DCAs and BBMs has been laid out, aligning across all relevant work packages. We have also established the implementation evaluation framework including harmonization of variables and establishing the Community of Practice (CoP) process model and governance structure, including framework for documentation and sharing of implementation learnings.
The first version of the Data Map for existing data has been completed, and we have created an initial Data Flow overview that tracks how data at this stage of the project is currently being collected, shared, and managed. Development and/or testing of predictive algorithms/models was conducted in parallel in existing observational cohorts (early risk and disease detection) and multidomain lifestyle-based intervention RCTs (response to intervention).
To ensure the quality of the AD-RIDDLE toolbox and to provide ethical guidance on potential socio-ethical implications of the project, a review of relevant literature was conducted to explore the ethical concerns linked to the development and implementation of population-level health screening approaches for AD/dementia risk. In combination with the Public Involvement work and a policy and practice review, the findings will inform the AD-RIDDLE toolbox design.
A scoping review of funding models was conducted, with emphasis on health impact bonds in health intervention programs. A health economic model for dementia prevention has also been developed by integrating the effects of cardiovascular disease.
Furthermore, we have conducted an assessment of health technology assessment (HTA) evidence requirements across Europe relevant for the AD-RIDDLE toolbox development, and a HTA Standing Forum was set up.
Work has begun on the sustainability workstream to identify, prioritise and select the project assets in advance, with the aim of maximising the sustainability of AD-RIDDLE and its impact on the field.
The AD-RIDDLE modular digital engagement platform will be customizable to each clinical site and is being co-designed with sites to ensure its effectiveness, cultural relevance, and compliance with local laws and regulations. This will also ensure that the platform can remain at the involved clinical sites as an enduring resource after the conclusion of AD-RIDDLE.
We are developing an innovative integrated framework for two related sets of objectives: validation of Digital Cignitive Assessments and Blood Based Biomarkers as new tools for AD diagnostics (and exploratory prediction/prognosis), and evaluation of their implementation in real-world settings. This is crucial to bridge the current gap between AD diagnostic validation and implementation evaluation studies. A one-size-fits-all approach would not recognize that health-care systems have differing needs and preferences. AD-RIDDLE real-world testing will thus use a more customized approach in which clinical sites can choose from DCA and BBM options to suit their needs, while following the principles of harmonisation outlined in the core protocol.
AD-RIDDLE is also connecting prediction and prevention via optimized use of data from existing observational cohorts and randomized controlled dementia prevention trials from several European countries. The new real-world testing of DCAs and BBMs will additionally contribute to these data analyses.
We are developing an innovative integrated framework for two related sets of objectives: validation of Digital Cignitive Assessments and Blood Based Biomarkers as new tools for AD diagnostics (and exploratory prediction/prognosis), and evaluation of their implementation in real-world settings. This is crucial to bridge the current gap between AD diagnostic validation and implementation evaluation studies. A one-size-fits-all approach would not recognize that health-care systems have differing needs and preferences. AD-RIDDLE real-world testing will thus use a more customized approach in which clinical sites can choose from DCA and BBM options to suit their needs, while following the principles of harmonisation outlined in the core protocol.
AD-RIDDLE is also connecting prediction and prevention via optimized use of data from existing observational cohorts and randomized controlled dementia prevention trials from several European countries. The new real-world testing of DCAs and BBMs will additionally contribute to these data analyses.