RealiseD – Comprehensive methodological and operational approach to clinical trials in rare and ultra-rare diseases

RealiseD implements a collaborative and compRehensive mEthodological and operational Approach to cLinical trIalS in rarE Diseases enabling timely drug development and approval centred on patients’ needs with high level of evidence reachable in a limited environment. 

• Operational Strategies: 
  • Developing systematic patient referral procedures. 
  • Certifying clinical sites and addressing gaps in conducting U(RD) clinical trials, using 4 diseases from 4 European Research Networks (ERNs) as case studies. 
• Methodological Innovation: 
  • Optimising statistical and quantitative methods for U(RD)-CT design and analysis refined over the last decade. 
  • Streamlining the regulatory pathway for drug development through these approaches. 
• Collaborative Framework: 
  • Engaging regulators, HTA bodies, and other stakeholders in a public-private consortium to co-create methodologies and operational frameworks through iterative processes. 
  • Reducing uncertainties in U(RD) drug development to incentivise pharmaceutical industry involvement. 
• Global Impact and Sustainability: 
  • Leveraging international efforts to address challenges in U(RD) drug development beyond geographical boundaries. 
  • Creating and deploying playbooks to ensure visibility, readiness, and stakeholder acceptance of innovations. 

The core of the project operational approaches includes the systematic procedures for patients’ referral, the certification of clinical sites and filling the gaps for successful development of rare and ultra rare diseases (U)RD’ clinical trials using 4 (U)RD diseases from 4 European Research Networks (ERNs).  

RealiseD methodological teams will optimise innovative statistical and quantitative approaches for design and analysis of (U)RD-CTs developed in the past 10 years and refined in the last years to facilitate the regulatory pathway for innovative drug development. RealiseD is implemented in a public private partnership consortium including regulators and HTA bodies representatives to co-create operational and methodological approaches in an iterative procedure using a multistakeholders’ agreement process. RealiseD will increase the incentives and motivation for the pharmaceutical industry by reducing many uncertainties on the path of drug development in (U)RD that will follow widely accepted rules.  

To achieve these innovative approaches, RealiseD will capitalise on an international multistakeholders effort as the problem in (U)RD drug development cannot be solved in a restricted geographical area. With the development and deployment of playbooks arising from the co-created developments, the project will ascertain visibility and readiness of the innovations. The overall ambition of RealiseD is to change the paradigm of CT design for U(RD) by enlarging the spectrum of methodological and operational approaches and to establish a sustainable, innovative, and optimised CT paradigm for U(RD) medicinal product development programs, while maximising the acceptance by all stakeholders. 

RealiseD consortium  

RealiseD brings together a consortium of key actors and stakeholders that altogether populate the competency areas required to accomplish the project objectives. In particular, public and private partners complement each other and underline the value of the widespread partner composition across sectors established; clinical partners will bring the necessary in-depth understanding of the clinical context and will be instrumental in establishing the clinical. As part of the European Reference Networks (ERNs) they will leverage the expertise and registries built by the ERNs towards the challenges to be addressed. The participation of EMA and The independent Institute for Quality and Efficiency in Health Care (IQWiG) at second stage is a major achievement of the consortium of the project. 

EATRIS Role 

To make the knowledge generated by RealiseD transferable to other interested parties involved in (U)RD drug development, EATRIS will lead the “Innovation readiness and Playbooks” Work Package (WP9). The Playbooks will contain innovative tools, methodological and operational products, simulation workflows, decision trees and other resources generated by RealiseD for facilitating an efficient design and adoption of innovative methodological approaches for designing and performing CT in (U)RD.  

The specific objectives are: (1) to co-create with project partners, playbooks as a user-friendly and iterative resource in a multi-stage process, where these playbooks will be assembled, aligned with other initiatives in the ecosystem (i.e. Horizon Europe EU-funded projects) and tested by end users; (2) to design the playbooks for an easy adoption by the U(RD) community assessing their usability and relevance (future proof) for facilitating novel CT designs for U(RD); (3) to create a virtual platform and design a sustainability plan for playbooks deployment with the goal of facilitating knowledge, tool sharing and playbook deployment.