The “Virtual Physiological Human: DementiA Research Enabled by IT” (VPH-DARE@IT) project aims to provide a systematic, multifactorial and multiscale modelling approach to understanding dementia onset and progression. It will explore the lifestyle and environmental factors that predispose to its development, and will deliver more objective and accurate differential diagnosis than what is available thus far in Europe, by shortening the current average 20-month time lapse between the onset of cognitive and memory deficits and its specific clinical diagnosis.
The project will deliver the first patient-specific predictive models for early differential diagnosis of dementias and their evolution. Its mechanistic/phenomenological models of the ageing brain account simultaneously for the patient-specific multiscale biochemical, metabolic and biomechanical brain substrate, as well as for genetic, clinical, demographic and lifestyle determinants. It investigates the effect of metabolic syndrome, diabetes, diets, exercise, and pulmonary conditions on the ageing brain, as environmental factors influencing onset and evolution of dementias.
An integrated clinical decision-support platform will be validated/ tested by access to a dozen databases of international cross-sectional and longitudinal studies, including exclusive access to a population study that has tracked brain ageing in more than 10,000 individuals for over 20 years (Rotterdam Study). This will be first integrative and validated multiscale modelling platform for biomedical research and clinical decision support, underpinned by a set of unique databases and modelling paradigms.
The project responds to the European Parliament's 2011 resolution for a European Initiative on Alzheimer's disease and other dementias, and the EU Year of the Brain 2014 Initiative.
Enabling more objective, earlier, predictive and individualised diagnosis and prognosis of dementias will support health systems worldwide to cope with the burden of 36 million patients that, due to ageing societies, will increase to 115 million by 2050. Worldwide costs are estimated at €450 billion annually. In 2012, the WHO declared dementia a global health priority.
The project is funded by the EC: programme acronym: FP7-ICT, sub-programme area: ICT-2011.5.2
Description of target users and groups
From early in the project we will engage with strategically important bodies like clinical and industrial users or health system and health policy decision makers, as well as software engineers, biomedical researchers and clinical staff.
The three main target markets of VPH-DARE@IT results are:
1) The industrial/commercial/non-healthcare market includes products that do not directly address health service provision. One segment of this market is interdisciplinary medical research, which can make use of the multiscalar models validated by VPH-DARE@IT. Potential users are the pharmaceutical companies, which could accelerate the drug development process based on the VPH-DARE@IT models. Another segment of this market – medical devices – is also expected to be particularly relevant. The non-healthcare market is an explicit target for exploitation and we expect the potential there to be significant.
2) The clinical/healthcare market is one in which VPH technology is deployed by healthcare providers; the decision support tools and systems directly support services provided to the patient at the point-of-care. This market can have two segments. One involves VPH technologies being purchased directly by health service providers. In the other segment, the VPH technology is only an intermediate good, which serves as input to larger, even more integrated health IT systems then sold to health services providers. In this segment, the customer is the medical IT industry rather than the clinical world directly. In both segments, clinicians are the end-users of the technology and thus clinical achievements are of pivotal importance to the potential for deployment and market penetration. The VPH-DARE@IT outcomes will target both segments, albeit a connection to or even integration with routine clinical information systems is clearly preferable, because this will allow immediate access to and making use of the respective patient’s individual data.
3) The scientific market refers to academic achievements related to the VPH-DARE@IT project. In contrast to the other two markets, the scientific market is easily penetrated already during the project lifetime, keeping Europe at the frontline of innovative simulation and modelling research in the VPH field. Rather than specific technology artefacts, the product in this market is the research activity itself, which is exploited by the scientific community in advancing their agendas.
Description of the way to implement the initiative
The consortium assembles highly recognised engineering, physical, biomedical and clinical scientists, and industrial partners experienced in exploiting VPH technologies in healthcare. Co-operation with infrastructure projects like VPH-Share, related international Physiome efforts, and other dementia research consortia is assured, allowing European researchers from different disciplines to contribute to share resources, methods and generate new knowledge.
The researchers will draw on historical data from over 20,000 patients across Europe to build their model. In addition, three studies involving 150 patients will test hypotheses on contributory factors for dementia.
Risks will be carefully evaluated and reviewed at regular project board meetings and solutions to any potential risk will be proposed. The Coordinator will organise regular meetings to ensure good communication between the partners. Project goals, planning, rules and way of working were established during the kick off meeting. The Coordinator will manage the communication between the project partners and with the European Commission. An IT infrastructure (EMDESK) is available and accessible by all partners.
The VPH-DARE@IT research platform will integrate the efforts of the rest of project partners and other open source tools already available that focus on dementia research, providing a single framework where new generation workflows will be created focusing on multiscale patient specific treatment for dementia. The specific objectives of this work are to:
- Develop a workflow-oriented and extensible framework for clinical researchers in dementia;
- Develop a workflow-oriented and extensible framework for VPH modelling researchers in dementia;
- Define interoperability mechanisms for leveraging functionality from other open source frameworks in dementia research;
- Define and implement integrative pipelines for data processing in VPH-DARE@IT;
- Support the interaction and integration of such frameworks with the VPH-Share data sharing infrastructure;
- Support data-provision centres in VPH-DARE@IT to federate their databases through the VPH-Share infrastructure.
A widely accepted software decision-support tool for diagnostics of dementias is not yet available. There is a clear need for a tool that is able to integrate heterogeneous information measured from patients and provide a risk score for each patient. The lack of such tools has been identified as a major challenge with high impact. This project develops a software tool that can be used for supporting early differential diagnostics of dementias. In order to enter clinical practice, the tool must be simple to use and provide information that is relevant for making diagnostics decisions. In short, clinical user requirements are central to the tool’s design and implementation.
The project will provide a research platform to generate information (e.g. biomarkers & measures) relevant for diagnostics or monitoring of disease progression. On the other hand, the clinical decision-support tool can generate information that is relevant for disease modelling purposes. Therefore seamless connectivity of the research and clinical platforms must be guaranteed.
Considering the effectiveness of various treatments (medication & psychosocial care), they should be started as early as possible. If patients first enter the hospital when their memory is already severely affected, it tends to be too late for starting some of the treatments. Therefore, cost-efficient approaches for detecting high-risk patients and channelling them to detailed diagnostics studies at an early phase are welcome. In addition to expensive governmental dementia screening programs, citizens should be empowered to screen their own health and risk for certain diseases. This project will also demonstrate the use of a portal designed for citizens to evaluate their risk for dementias and ways to integrate this portal to the research and clinical platforms. The clinical decision-support tool will be an extended version of the PredictAD tool developed in the previous VPH project. Novel features will be implemented into the tool, such as tools for differential diagnostics. The portal for citizens will be based on previous work done at VTT and UEF.Technology choice: Proprietary technology, Open source software
Main results, benefits and impacts
Health technology assessment (HTA)
The project will develop a socio-economic and technology assessment method (HTA) that includes also a prospective clinical impact analysis approach. From a user, stakeholder and market perspective, this task will:
a) Develop upon and adapt in the VPH and other contexts proven approaches, methods and tools to the specific environment and objectives of this work package;
b) Establish a set of meaningful criteria and their measurement instruments and processes that are robust to demonstrate socio-economic benefit-cost impacts;
c) Incorporate health economic considerations underlying the onset and the progression of dementia in a European context.
The health technology assessment (HTA) will serve as a support tool delivering information useful for health system actors and decision makers to allow them to arrive at more factual, evidence-based decisions and policy measures, supporting the RTD WPs in developing business cases when implementing the VPH-DARE@IT models, tools and decision-support systems.
This work will involve applying proven HTA methods, to be adapted towards the specific characteristics of VPH research. Project partners will work together and results from work on verification of simulation model approaches, structures and functionalities, and validation of model outputs will become a key input. Literature reviews, market data – where available – and empirical methods like face-to-face or written interviews and expert discussions, semi-structured telephone conferences or even focus group approaches may become applied to gather further evidence and to better understand exploitation options and aspirations of project partners and other market actors.
To support these goals the VPH-Dare will make use of VPH-Share infostructure which provides a base for the deployment of both computational and storage resources including a number of out of the box tools that will speed up the process to incorporate data, develop research workflows and support the clinical tool, VPH-Share components will be extended with other tools, e.g. XNAT, when relevant to generate the project expected outcomes.
VPH-DARE@IT’s aim is to enable more objective, earlier, predictive and individualised diagnoses and prognoses of dementias to cope with the challenge of an ageing European society.
Currently doctors rely on basic cognitive tests and conventional brain scans to diagnose dementia, but these are not able to recognise the disease at an early stage. If a much wider range of markers can be identified which enable a better and earlier diagnosis, then doctors will have more time to delay the progression of the disease.
The expected impact of the project will influence the scientific, clinical and industrial communities across Europe and internationally to improve the healthcare of dementia patients. This would both improve patients’ quality of life, and also reduce the burden on carers and the costs of supporting people with dementia.
|Measure of Success||Indicator of Impact|
|Overall clinical impact|
More objective, standardised differential assessmentTime lapse between the onset of cognitive and memory deficits and its first diagnosis.
|Enable earlier diagnosis by reducing the current 20-months time lapse from first admission to diagnosis|
Scientific impact – dementia model
Deliver a systematic, multifactorial and multiscale modelling approach to understanding dementia;Explore the lifestyle and environmental factors that predispose to its development
At least 2 clinical and 2 technical landmark publications describing the VPH-DARE@IT strategy for multiscale multifactorial and multi-paradigm dementia modelling and its application/impact in brain disease.
|Industrial impact||Technology uptake in the form of modules or systems: no. of patents and licence agreements|
At least one success story in the form of tech transfer agreements and patents available at the end of the project.Fast concept-prototype-product cycle thanks to VPH development frameworks.
|Dissemination impact||Dissemination to and engagement with the wider community|
Presence on the internet, existence of newsletters, production of a video for the general public, participation in wider dissemination events.
|Training impact||Contribution to and organisation of training events|
At least yearly training events in three areas: software platforms
(Developer/User Workshops), clinical uptake (e.g. Clinical Training Courses), general scientific dissemination (EIBIR Summer School)
|Infrastructural impact||Open source platform for VPH modelling and image-based biomarker extraction in dementia available for the VPH community|
GIMIAS and Nifty well-documented & supported, integrated in VPH Toolkit, widely used in the community
VPH-share infostructure demonstrates scalability and reusability with large databases in VPH-DARE@IT
Return on investment
The project will reduce the costs of supporting people with dementia.
Track record of sharing
Within VPH-DARE@IT activities, dissemination will aim at facilitating the communication effort of the consortium with a range of stakeholders, including:
- The European Union as a whole;
- The academic community (via promoting the publication and visibility of project output);
- The clinical end-recipients of the know-how developed;
- The industrial partners interested in the uptake of the new knowledge produced.
This will involve also the outreach to related VPH projects, the VPH Network of Excellence, and the VPH Institute, the DISCIPULS support action, and the infrastructure IP, VPH-Share. VPH-DARE@IT will engage actively with the community through its core partners’ membership in the VPH Institute, which is expected to organise the future VPH conferences.
We will also engage in dialogue with projects and researchers modelling the impact of environment on health:
- Socio-economic environmental large databases such as the German Socio-Economic Panel Study (SOEP) by the German Institute for Economic Research (data of over 26 years for the same person; contacts established);
- The multi-centre RCT Finnish Geriatric Intervention study to prevent cognitive impairment and disability (FINGER) combining comprehensive clinical data, environmental demographics, etc.;
- The Rotterdam Study, a prospective cohort study comprising a total of 10 994 subjects and data on current health status, medical history, smoking habits, socio-economic status, drug use, dietary habits, alcohol consumption, and physical activity;
- Environmental agencies such as the German Federal Environment Agency (UBA), Unit Exposure Assessment and Health Indicators (contacts established);
- National and regional patient/disease registries (e.g. SveDem – Swedish Dementia Registry with 16 000 registered patients;
- Quality of healthcare registries;
- EU FP7 projects in the research area environment and health (e.g. environmental modelling for the mitigation of health risks (EO2HEAVEN), on integrating environmental and health data, and on the FP7 call for funding of the European Exposome (ENV.2012.6.4-3 Integrating environmental and health data to advance knowledge of the role of environment in human health and well-being in support of a European exposome initiative).
- Breakthroughs in IT for healthcare will come from interdisciplinary clinically-led yet IT-enabled approaches to healthcare, not an IT-centric approach, to innovation where clinical drivers are essential. This requires funding with the scale of ambition of Integrated Projects and breaking the boundaries between ICT and Health funding streams. Future projects need to enable simultaneous methodological development and rich clinical data collection.
- Advanced ICT for Health, particularly in the area of the Virtual Physiological Human, requires specific Health Technology Assessment strategies that may not fit within the standard patterns of traditional HTA. It requires flexible and intertwined cycles of technological innovation and clinical evaluation that calls for, cross technical-clinical partnerships and long-term funding schemes.
- Patient-specific physiological modelling plays a crucial role, not only in diagnostics and therapeutics, but also in deeper disease understanding and clinical research. As such, it needs to permeate future clinical research calls and a timeframe for “deployment” cannot be imposed in this area.