Work packages (WPs) are major sub-divisions of the PRISM project where the actual work is performed. Every WP has two designated WP leaders and a certain number of other beneficiaries who contribute with specific tasks.
WP1 Consortium management and governance
Effective project management is a central element of successful research. This particularly applies to large research projects entailing a substantial amount of administrative work. The management WP makes sure that the project achieves its objectives and delivers its milestones and deliverables on time, within budget and with highest quality. It is furthermore concerned with communication, reporting, meeting organisation, financial management and intellectual property rights. The responsibility for project management lies primarily with the coordinator and project leader who are supported by concentris.
WP2 Scientific consensus (clinical/pre-clinical) on study designs, instruments and methodology
WP2 will create and govern the scientific rationale and consensus for selecting the approaches for the clinical and preclinical deep phenotyping studies that are performed in WPs 4 and 6. This WP will utilize already available scientific literature and expertise within the consortium to select study designs, instruments, and methodologies directed at obtaining homologous and robust clinical and pre-clinical measures for social withdrawal, attention, working memory, and sensory processing. In this WP it is solely intended to align and harmonize specific objectives and tasks between the clinical and pre-clinical WPs 4 and 6. Consequently, there will be a strong reach into operative tasks and objectives of these WPs.
WP3 Data engineering and statistics to allow integrated analysis of data sets
WP3 will develop a statistical approach for fusion of quantitative modality-specific biological measurements relative to behavioural parameters of social withdrawal, attention, working memory, and sensory processing and link these to behavioral data and clinical assessments. We will use data-driven clustering of individual domain data validated against symptom constellations to identify the highest predicting quantitative domain in patients stratified for low versus high social withdrawal. Moreover, multi-modal data fusion approaches are applied to derive quantitative phenotypes across the different makes (behavioural, genetic, and imaging-derived) and validated against neuropsychiatric measures.
WP4 Clinical study implementation and operations
WP4 will validate clinically relevant biological substrates for social withdrawal and cognitive function through the use of quantitative technologies including behavioural, functional MRI and electroencephalography (EEG) paradigms. This will be achieved by conducting a clinical investigation in a multi-center clinical study to evaluate the relationship between social withdrawal and cognitive performance in SZ and AD patients.
WP5 Clinical harmonization of experimental approaches
WP5 will utilize already available patient cohort infrastructures within Europe to analyze or complement existing data on social withdrawal and cognitive deficits (sensory processing, attention, working memory) within samples of SZ, AD and MD. Using already available biological and genetic data, coupled with results from world-wide genetic consortia, we will explore the biological substrate of social withdrawal and cognitive deficits in the different disorders through cohort data mining and PheWAS.
WP6 Pre-clinical harmonization of experimental approaches
The overall aim of WP6 is to set up preclinical proxy indicators of social withdrawal in mice and determine which cognitive domains might be impacted by such impairments. The biological substrates of social withdrawal identified in the clinical work packages by correlating genetic and molecular findings to behaviour and function will then be interrogated with this preclinical test battery to determine the degree of translational validity of these findings.
WP7 Engagement with regulatory groups, agencies and other stakeholders
WP7 takes care of three aspects of PRISM’s structure and outreach: (1) Ethical requirements for the work undertaken by PRISM; (2) the impact of PRISM outcomes from the patient`s perspective; and (3) initiate the regulatory path for clinical readouts identified by PRISM. Many clinical trials in brain disorders have focused on primary outcomes that are marginally relevant to the affected person´s quality of life (e.g. 20% reduction on a general psychopathology scale in SZ). The lack of ecological and pragmatic outcomes that translate to real-world advantages in many trials may be due to a lack of involvement of the individuals affected by the diseases, the patients themselves and their families. Involvement of such stakeholders is a key component of this WP. In addition, WP7 will liaise with regulatory agents to pave the regulatory path for clinical readouts relevant to acute social withdrawal as well as attention, working memory and sensory processing deficits across various disease conditions. Clinical trial use of primary outcomes based on biomarkers across different disorders is considered an innovative development methodology that will require scientific advice from EMA for future qualification of novel methodologies for medicine development.
WP8 Dissemination, training and communication
WP8 will increase the visibility of PRISM by reaching out to the scientific community, industry, patient organisations and other interested or potential stakeholders. A communication plan will be implemented. PRISM’s findings will be disseminated to the public through high-impact, international research publications, conferences and articles in the laymen press.