Periodic Reporting for period 3 - PRISM (Psychiatric Ratings using Intermediate Stratified Markers - Sofia ref.: 115916)
Berichtszeitraum: 2018-04-01 bis 2019-09-30
This lack of understanding of the root biological causes is one of the reasons behind the dramatic slowdown in the development of new drugs to treat neuropsychiatric disorders. Historically, many of the major drug classes for psychiatric disorders were discovered as a result of chance observations. By contrast, modern drug design aims to reduce this risk of attrition by targeting a known biological process and then closely monitoring and quantifying the treatment effects.
The overall objective of this project is to develop a quantitative biological approach to the understanding and classification of neuropsychiatric disease with the goal to accelerate the discovery and development of better treatments for patients. The concept of our proposal is to define a set of quantifiable biological parameters for social and cognitive deficits to stratify and differentiate Schizophrenia (SZ) and Alzheimer’s Disease (AD). The following specific objectives have been addressed:
1.) Proof-of-concept analyses to cluster and differentiate SZ and AD patients on the basis of quantitative biological parameters.
2.) Explore dimensional relationships between pathology and social withdrawal.
3.) Develop deeper understanding of the quantitative biology of social withdrawal using clinical data from SZ, AD and MD patients and by establishing a network of pre-clinical research sites able to perform high quality back-translation studies.
4.) Develop a path towards recognition of social withdrawal as a registrable symptom across disorders.
According to the original call text, PRISM has been anticipating a phase 2 project during which a sustainability roadmap will be implemented. As part of phase 1, the outline of this roadmap has been generated.
PRISM bridged the important translation gap between discovery and the validation of biomarkers and their associated technologies to a point where they can be deployed reliably and effectively across the network. The PRISM network established that quantitative biological parameters can be used to effectively stratify patients using biomarkers for social functioning.
Back-translation of human biological substrates for social and cognitive deficits has been performed using core technologies. Novel technologies have been implemented and validated to longitudinally assess social group behaviour and sensory processing deficits to provide better predictive preclinical model systems.
We have and continue to influence the thinking of patients, carers and the public establishing that neuropsychiatric disorders are ”real” with biomedical substrates similar to other physical illnesses thereby reducing the stigma associated with mental disorders. We have made real progress in encouraging the clinical community to consider neuropsychiatric disorders through a more quantitative lens (e.g. the journal Science highlighted PRISM’s project launch and feedback from stakeholders). Our quarterly Newsletter has been distributed to 20,000 stakeholders through ECNP, and presentations on the PRISM project were given at patient meetings and international conferences ensuring that we reach our target audiences. In addition, all PRISM procedures and feedback from stakeholders have been published in a special issue of Neuroscience & Biobehavioral Reviews on the PRISM project, including 13 manuscripts.
PRISM showed that using a smartphone-based app to measure social functioning across large populations containing subjects with neuropsychiatric diseases is feasible and could be more widely used in future research. PRISM has also initiated the dialogue with the EMA Innovation Task Force with respect to the qualification of a digital biomarker/endpoint for social functioning based on the BEHAPP smartphone data. The EMA ITF provided encouraging feedback, namely that we are progressing down to the path to being able to establish the app outcomes as a qualified biomarker. The PRISM consortium presented the PRISM results at an EMA organized symposia at the 2019 ECNP Congress. Continuing the process is, therefore, clearly a key component to the strategy needed to deliver the concept of PRISM into an effective approach deployable by the various stakeholders for the benefit of patients across Europe.