WP2 – Scientific, Regulatory and Operational Methodology
EU-PEARL has developed this comprehensive glossary of terms with the objective of educating people and building knowledge 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
WP4 – Integrated Research Platform for Major Depressive Disorder (MDD)
Depression, is a serious and potentially life-threatening condition affecting up to 1 in 6 adults at some
point during their lifetime. While considerable efforts over the past 40 years have led to the
introduction of safer and better tolerated pharmacological treatments, they only achieve sufficient
symptom reductions in about 50% of the patients with this disabling condition. However, developing
new drugs is very time consuming and expensive. New approaches to more quickly and more
efficiently detect the most promising new drug candidates are therefore needed. To address this, the
EU Patient-cEntric clinicAl tRial pLatforms project (EU-PEARL) is developing what is called an
“integrated research platform” that provides a reusable infrastructure for screening, enrolling, and assessing/treatment of participants in a flexible and highly adaptive “platform trial”.
In this report, we present a draft of how we envision our “integrated research platform” for depression. Moreover, we have discussed this draft with the European Medicines Agency (EMA), the authority overseeing pharmaceuticals in the European Union. We present a summary of the advice we have received from EMA experts to ensure that the trial yields speedy results on the benefit of any new drug tested and maintains the highest ethical and safety standards. Moreover, we provide an outlook on how we intend to proceed as we are moving towards finalizing our project.
Read or download EU-PEARL- D4.3 Interim Report on TRD PRD master protocol
WP4 – Integrated Research Platform for Major Depressive Disorder (MDD)
This report gives the public information about an observational research study on difficult-to-treat depression. It is also written for people who take part in this study.The purpose of the EU-PEARL project is to develop a new way to screen, enrol and treat participants in clinical trials. A new way that is flexible, allowing the possibility to test several new treatments at the same time. For depression, these treatments are discontinued as soon as it becomes apparent that they do not work. The present study is part of this new framework design. Its purpose is to identify individuals with depression, who do not adequately respond to antidepressant medication,and offer them the possibility to participate in this new framework of clinical trials, where multiple medications for treatment resistant depression can be tested at the same time. A set of health outcomes directly reported by patients who experienced depression, that measure medication side-effects, symptom burden, functioning, recovery, social support and stressful life events are used in this study. The development of a new reusable approach to test multiple medications in individuals who do not adequately respond to antidepressant medication will help develop new treatments in this area of such medical need.
Read or download EU-PEARL’s D4.4 LNHS Readiness cohort protocol for MDD platform
Access Annex I LNHS Protocol ANNEX II. MADRSsigma ANNEX III.ICHOM PROMs ANNEX IV. ICHOM reference-guide