WP2 – Scientific, Regulatory and Operational Methodology
EU-PEARL has developed this comprehensive glossary of terms with the objective of educating people and building knwoledge around complex clinical trials. The document draws on external definitions from authoritative sources to propose a common use of terminology beyond the project’s scope. But the deliverable takes a step further and offers a wide range of materials (beyond terminology) to better understand the relevance and scope of master protocols and platform trials.
Read or download EU-PEARL Report on Terminology and Scenarios for Platform Trials and Masterprotocols (D2.1)
WP2 – Scientific, Regulatory and Operational Methodology
As new complex, innovative designs such as platform trials emerge, clinical operations best practices need to be reviewed to address the new challenges they bring. Clarity on roles and responsibilities, effective resource planning, a sound governance structure, a strategic approach to vendor management and robust training for all key stakeholders are some of the topics which need to be taken into account for multi-sourced, multi-company platform trials to work.
Read or download EU-PEARL Clinical Operations Best Practices Report (D2.2)
WP4 – Integrated Research Platform for Major Depressive Disorder (MDD)
In the present report, the evidence on treatment response in major depressive disorder (MDD) has been systematically reviewed and summarized. In addition, a Delphi-method-based consensus document on treatment-resistant depression (TRD) and partially responsive depression (PRD) has been elaborated. The main aim is to establish an explicit consensus on defining treatment resistance in MDD and to deliver operational criteria for randomized clinical trials, especially for Phase II/Proof of Concept clinical trials for new medications (or, potentially, repurposed medications) for TRD and PRD. The core gaps in knowledge and the main uncertainties of currently used TRD and PRD definitions have also been identified and discussed, highlighting the absence of clear definitions and, importantly, a discrepancy between the most commonly used definitions and the most frequent inclusion criteria for clinical trials.
Read or download EU-PEARL Report on Consensus Disease Definition for TRD and PRD (D4.1)
WP5 – Integrated Research Platform for Tuberculosis (TB)
Integrated Research Platform (IRP) is a novel concept for development of medical innovations in the pursue of enhance efficiency to design and implement complex clinical trials. However, there is no tool available for evaluating the capacity and preparedness of trial sites to conduct TB drug development trial within the IRP environment. We have reviewed current global resources to produce this handbook which is structured in 5 main sections corresponding to 5 domains for capacity and readiness assessment: site; microbiology laboratory; trial pharmacy; data management; ethical considerations. These domains are evaluated through a ‘readiness assessment checklist’ that allows the extraction of a minimum set of key indicators used to calculate a readiness score. Such score allows comparisons across sites. This Handbook represents an innovative approach that may help preparing sites for future TB research.
Read or download EU-PEARL Capacity Building and Assessment Handbook for site readiness (D5.2)
WP6 – Integrated Research Platform for Non-Alcoholic Steatohepatitis (NASH)
The term NASH refers to the severe disease course of non-alcoholic fatty liver disease (NAFLD), leading to both liver related and non-liver related morbidity and mortality. NASH constitutes a significant unmet medical need with a burgeoning field of clinical research and drug development. In this instance, Integrated Research Platforms (IRP) using master protocols and a supporting research framework represent a unique opportunity to accelerate drug development while lowering overall costs and creating a more patient-centric environment. This deliverable provides a comprehensive and nuanced assessment of the NASH clinical development landscape, and, in particular, on the endpoints generally used in NASH trials and how they might be adapted to an IRP master protocol. Furthermore, the main design, statistical and regulatory challenges and opportunities for a NASH IRP trial are discussed, alongside with the potential barriers that might be encountered.
Read or download EU-PEARL Report on Challenges and Clinical Trail Scenarios in NASH specific IRPs (D6.1)
WP7 – Integrated Research Platform for Neurofibromatosis (NF)
Integrated Research Platform (IRP) is a novel concept for development of medical innovations in the pursue of enhance efficiency to design and implement complex clinical trials. The term NF englobes rare and hereditary conditions, often with a high variability in expression and severity of symptoms. The aim of this deliverable is to reach consensus on the most important manifestations of NF to select for clinical trial and to share the findings with the wider scientific and medical community. Through a multi-staged modified Delphi procedure, a consensus meeting and a survey for patient representatives, EU-PEARL’s WP7 has reached a common understanding on how to group the various NF manifestations under the same platform trial, followed by a prioritization of these groups into a final selection of manifestations to be included into the IRP.
Future efforts will be focused on peripheral benign nerve sheath tumors, sarcomas, cutaneous manifestations and high-grade gliomas for NF1, tumors for NF2, and pain for Schwannomatosis.
Read or download EU-PEARL Report on the Consensus Definition of Current Challenges in NF (D7.1)
Project – EU-PEARL 1st Technical Report: Milestones, deliverables and major achievements
In its first year, EU-PEARL has focused on laying a foundation for the creation of generic and disease-specific IRP frameworks and common tools, while generating awareness on the project and the advantages of adaptive platform trials. Besides developing generic “data management and governance” guidelines, a comprehensive glossary with key terminology and a report on best practices in platform trial operational aspects, disease-specific teams, in collaboration with expert methodologists, have started to address trial design challenges and master protocol development in each of the four disease areas. EU-PEARL also organised 4 successful online Stakeholder Workshop sessions on October’20 focused on: regulatory & ethical issues, methodological challenges and patient engagement priorities for IRP development.
Read or download EU-PEARL_PR01_Technical report_PUBLISHABLE_SUMMARY