The success of this Project will be underpinned by the coordinated activity of the different Work Packages (WPs). Although the 8 WPs are described separately below, to achieve the Project’s goals, close collaboration and cross-cutting actions of the different WPs are crucial.
WP1 integrates the scientific input to the project and addresses the central questions in AD disease modification that will drive the design of the EPAD adaptive clinical trial: who are the subjects, how should they be assessed, and with what should they be treated?
- To define a spectrum of individuals at risk of developing dementia due to AD.
- To define the evaluation criteria for inclusion of participants into the EPAD Register, EPAD Cohort and EPAD Trial, and the relevant biomarkers, clinical assessments and endpoints.
- To assess and select potential trial mechanisms and compounds, through a Clinical Candidate Selection Committee.
- To establish and coordinate four Scientific Advisory Groups (SAGs) referring to key scientific areas that gather the needed, high-level scientific knowledge to support decisions made in WP1.
- Andrew Satlin (Eisai)
- Simon Lovestone (University of Oxford)
- Gary Romano (Janssen)
This WP is the anchor for knowledge management and receives all data from the EPAD Register, Cohort and Trial for analysis, to continually inform disease modelling and adaptive trial design decisions. WP2 will gather the tools and resources that will be used for disease modelling, assess and prepare them for exploitation and set up procedures to design the adaptive trial.
- To develop and optimize disease modelling and simulation software supporting risk modelling and adaptive clinical trial design and updates.
- To develop disease and risk modelling capacity based on existing and acquired data via EPAD Cohort and Trial activities informing scientific assessment in WP1 and trial design updates.
- To build the interventional adaptive trial design and needed methodology, providing updates to the design, analysis of new interventions and of existing compounds.
- Scott Berry (Berry Consultants)
- Shobha Dhadda (Eisai)
- Adrian Mander (MRC)
- Philip Hougaard (Lundbeck)
WP3 will create and maintain an EPAD Register, in the form of full “fingerprinting” of parent Cohorts (approximately 24,000 participants).
- To provide the methods and tools to identify, characterise and select Parent Cohorts suitable for contributing to the EPAD Register.
- To provide the methods and tools to identify and select suitable participants from Parent Cohorts to build the EPAD Register, enabling the appropriate data discovery/sharing capacity and underpinning policies.
- To define operational processes and arrangements for maintenance and replenishment of the EPAD Register.
- Pieter-Jelle Visser (Vu-Vumc)
- Gerald Luscan (Pfizer)
WP4 will initially focus on selection and certification of the EPAD Trial delivery centres and establish the EPAD Cohort protocol early in the project. Subsequently the design and execution of the Proof-of-Concept (PoC) study will be their main focus. WP4 will oversee the execution of the protocols for the EPAD Cohort and Trials and work with National/Regional Leads and Clinical Research Organisations (CROs) on qualification, establishment and training of the EPAD Trial delivery centres.
- To establish certified EPAD TDCs across Europe capable of recruiting the needed number of subjects for the EPAD Cohort and Trial.
- To establish the EPAD Cohort and related data flows, databasing infrastructure, quality control/assurance and monitoring procedures.
- To sign off the EPAD Cohort Protocol and implement it.
- To sign off the EPAD Trial Master Protocol and Appendices implement them.
- To establish a Principal Investigators Network supporting EPAD Cohort and Trial activities.
- Lisa Ford (Janssen)
- Craig Ritchie (University of Edinburgh)
- Catherine Debove (Boehringer)
- Miia Kivipelto (Karolinska Institutet)
WP5 provides professional project management to EPAD ensuring successful completion of the Project.
- To set-up a project management structure that ensures efficient operational and timely execution of the Project.
- To guarantee project is executed according to the work plan and scientific activities are managed efficiently.
- To manage resources, procedures and tools for ensuring that all expected results are delivered on time, with an adequate quality level and within cost, including risk management and quality control procedures on deliverables.
- To ensure effective communication and work dynamics between Participants to help drive the whole Consortium as a team towards successful completion of the Project.
- Carlos Diaz (Synapse)
- Serge Van der Geyten (Janssen)
This WP will lead and coordinate external dissemination activities, outreach to specific external stakeholders and the public health campaign with special emphasis on the importance of AD prevention. WP6 will also assess the impact and effectiveness of dissemination activities.
- To develop a dissemination and communication plan including objectives, target audiences, tools and activities.
- To develop and update the needed tools to implement the planned dissemination activities.
- To carry out a variety of dissemination activities aiming at maximising exposure of the project while optimising the project’s perception among the different target audiences.
- Sean Knox (Novartis)
- Jean Georges (Alzheimer Europe)
WP7 will analyse markets, stakeholders, incentives and schemes for pre-competitive intellectual property handling, in order to develop a viable business plan for sustainability of the EPAD ‘machine’ and network of centres beyond the time frame of the project.
- To study existing and emerging public-private partnership collaborative models that can be useful for the EPAD sustainability.
- To analyse the stakeholder types intervening in EPAD, their interests and incentives towards sustainability.
- To analyse and develop procedures for a pre-competitive space that caters to a variety of companies and therapies.
- To analyse and develop procedures that enable the EPAD infrastructure of TDCs to be sustained over time.
- To develop a solid business plan that enables transition of EPAD to the post-project phase for long term sustainability.
- José-Luis Molinuevo (BBRC)
- Frank Tennigkeit (UCB)
- Saira Ramasastry (Synapse)
WP8 will carefully study critical ethical, legal and social issues (ELSI) pertaining to the project and provide guidance on informed consent, privacy, disclosure of findings and data sharing.
- Define an EPAD ethics and information governance framework for recruiting from existing cohort studies.
- Develop a robust strategy for involving research subjects in the development of ethics procedures and research protocols.
- Investigate the ethical, legal and social implications of disclosure of biomarker results and the associated risk of AD dementia.
- Evaluate and compare the feasibility and impact of large-scale biomarker-testing within national health care systems.
- Investigate and advise on the recruitment of subjects for Phase 2 trials from existing cohort studies.
- Luc Truyen (Janssen)
- Shirlene Badger (University of Cambridge)
- Edo Richard (RUMC)
- Carol Brayne (University of Cambridge)