While randomized controlled trials (RCTs) remain the mainstay in drug development, approval, and reimbursement, the potential of real world data (RWD) to contribute to the understanding of drug effects is increasingly realized. Evidence, based on RWD – real world evidence (RWE) - can contribute significantly to the evidence to support decision making throughout all phases of (clinical) drug development, as well as improve efficiency in design and conduct of clinical trial programs. The aim of this project is to develop, implement and establish evidentiary standards and methods to address the data and evidentiary needs of regulatory authorities and HTA bodies towards a more efficient use of RWD for the development, registration and assessment of medicinal products in Europe (More-EUROPA).

The European Rare Diseases Research Alliance (ERDERA) aims to improve the health and well-being of the 30 million people living with a rare disease in Europe, by making Europe a world leader in Rare Disease (RD) research and innovation, to support concrete health benefits to rare disease patients, through better prevention, diagnosis and treatment. This Partnership will deliver a RD ecosystem that builds on the successes of previous programmes by supporting robust patient need-led research, developing new diagnostic methods and pathways, spearheading the digital transformational change connecting the dots between care, patient data and research, while ensuring strong alignment of strategies in RD research across countries and regions. Structuring goal-oriented public-private collaborations targeted at interventions all along the R&D value chain will ensure that the journey from knowledge to patient impact is expedited, thereby optimising EU innovation potential in RD. To support its ambition and missions ERDERA has been designed as a comprehensive and integrated ecosystem of which structure can be compared to an institute encompassing three main parts: (i) funding, (ii) internal (in house) Clinical Research Network that implements research activities targeting clinical trial readiness of RDs and accelerating diagnosis and translation of research discovery into improved patient care, and (iii) related supporting services (Data, Expertise, Education and Training) as well as an acceleration hub that serve external and internal RD community, all supported by all-embracing coordination and strategy and foundational (inter)national alignment.

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. The core of RealiseD 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, RealiseD 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 maximizing the acceptance by all stakeholders.

Measuring and quantifying how a patient feels or functions during treatment is an important endpoint in cancer clinical trials. It is generally accepted that the collection of PRO data in cancer clinical trials allows the inclusion of the patient’s voice in the risk-benefit assessment of therapies. However, no standards exist on how to analyse, interpret or report health-related quality of life (HRQOL) and other patient-reported outcomes (PROs). This initiative wants to pursue efforts in addressing the urgent need for standardization, by setting clear and validated standards that are tailored to and endorsed by all relevant stakeholders. With a strong international and multi-stakeholder Consortium, the initiative aims at finding consensus on suitable methods to analyse valid PRO objectives in cancer randomized clinical trials (RCTs) and ways to communicate these PRO findings in a standardized way that is understandable to all. To achieve this aim, SISAQOL-IMI will identify valid PRO research objectives and match these with appropriate statistical methods for PRO analysis in cancer RCTs. Translation to the estimands framework will be provided. Furthermore, the possibility of extending these recommendations to single-arm trial designs will be explored. Recommendations on clinically meaningful change for PRO instruments, as well as design considerations and ways for assessing quality of collected PRO data will be developed, and tools and templates for presentation and visualization of PRO findings freely made available. Strong emphasis is put on continuous collaboration with patient advocacy representatives throughout the project. Increased interpretability, adoption and full use of PRO outcomes for all stakeholders is expected by providing consensus-based and validated recommendations and communication tools for PRO data, ultimately resulting in better communication and shared decision making, improved outcomes, treatment satisfaction and care.