Methods for Stratification and Validation Cohorts: A Scoping Review.

Personalized medicine requires large cohorts for patient stratification and validation of patient clustering. However, standards and harmonized practices on the methods and tools to be used for the design and management of cohorts in personalized medicine remain to be defined. This study aims to describe the current state-of-the-art in this area.

Therapeutic hypothermia for acute ischaemic stroke. Results of a European multicentre, randomised, phase III clinical trial.

Introduction: We assessed whether modest systemic cooling started within 6 hours of symptom onset improves functional outcome at three months in awake patients with acute ischaemic stroke.

Patients And Methods: In this European randomised open-label clinical trial with blinded outcome assessment, adult patients with acute ischaemic stroke were randomised to cooling to a target body temperature of 34.0-35.

Evaluation of repositories for sharing individual-participant data from clinical studies.

Background: Data repositories have the potential to play an important role in the effective and safe sharing of individual-participant data (IPD) from clinical studies. We analysed the current landscape of data repositories to create a detailed description of available repositories and assess their suitability for hosting data from clinical studies, from the perspective of the clinical researcher.

Methods: We assessed repositories that enable storage, sharing, discoverability, re-use of the IPD and associated documents from clinical studies using a pre-defined set of 34 items and publicly available information from April to June 2018.

How the new European data protection regulation affects clinical research and recommendations?

Clinical research on human subjects or their data is confronted with conflicting requirements with, on one hand, the principle of open science (transparency and data sharing), the possibilities offered by big data and the reuse of healthcare or research data, and on the other, changes to the regulatory and legislative framework, including the general data protection regulation (GDPR). A roundtable was organized in Giens, France in October 2018 to identify problem areas, the need for clarification and streamlining, and to make recommendations to promote clinical research while ensuring a high level of patient protection. After details were given about these developments, the roundtable participants were able to propose recommendations, primarily (1) to clarify: what is considered anonymized data, and what is "public interest" within the meaning of the GDPR; (2) for the French data protection authority (CNIL) to continue preparing reference methodologies to simplify the approval system; (3) to promote the secondary use of data by making it easier to inform patients and obtain broad patient consent, by specifying the circumstances under which their withdrawal and opposition rights apply, so as to limit the risk of bias; (4) to facilitate access to data warehouses by providing technological and methodological aids.

European mental health research resources: Picture and recommendations of the ROAMER project.

As part of the Roamer project, we sought to have a picture of the available mental health research (MHR) funding, capacity-building and infrastructures resources and to establish consensus-based recommendations that would allow an increase of European MHR resources and enable better use and accessibility to them. The methods fell into three sections (i) a review of the literature, (ii) a mental health-related keywords search within the Cordis, On-Course and Meril databases which contain information on European research funding, training and infrastructures. These reviews provided an overview that was presented to (iii) two experts workshops with 28 participants drawn from academic which identified gaps and produced recommendations.

Sharing and reuse of individual participant data from clinical trials: principles and recommendations.

Objectives: We examined major issues associated with sharing of individual clinical trial data and developed a consensus document on providing access to individual participant data from clinical trials, using a broad interdisciplinary approach.

Design And Methods: This was a consensus-building process among the members of a multistakeholder task force, involving a wide range of experts (researchers, patient representatives, methodologists, information technology experts, and representatives from funders, infrastructures and standards development organisations). An independent facilitator supported the process using the nominal group technique.

A systematic literature review of evidence-based clinical practice for rare diseases: what are the perceived and real barriers for improving the evidence and how can they be overcome?

Background: Evidence-based clinical practice is challenging in all fields, but poses special barriers in the field of rare diseases. The present paper summarises the main barriers faced by clinical research in rare diseases, and highlights opportunities for improvement.

Methods: Systematic literature searches without meta-analyses and internal European Clinical Research Infrastructure Network (ECRIN) communications during face-to-face meetings and telephone conferences from 2013 to 2017 within the context of the ECRIN Integrating Activity (ECRIN-IA) project.

Specific barriers to the conduct of randomised clinical trials on medical devices.

Background: Medical devices play an important role in the diagnosis, prevention, treatment and care of diseases. However, compared to pharmaceuticals, there is no rigorous formal regulation for demonstration of benefits and exclusion of harms to patients. The medical device industry argues that the classical evidence hierarchy cannot be applied for medical devices, as randomised clinical trials are impossible to perform.

Evidence-based practice within nutrition: what are the barriers for improving the evidence and how can they be dealt with?

Background: Evidence-based clinical research poses special barriers in the field of nutrition. The present review summarises the main barriers to research in the field of nutrition that are not common to all randomised clinical trials or trials on rare diseases and highlights opportunities for improvements.

Methods: Systematic academic literature searches and internal European Clinical Research Infrastructure Network (ECRIN) communications during face-to-face meetings and telephone conferences from 2013 to 2017 within the context of the ECRIN Integrating Activity (ECRIN-IA) project.

Barriers to the conduct of randomised clinical trials within all disease areas.

Background: Randomised clinical trials are key to advancing medical knowledge and to enhancing patient care, but major barriers to their conduct exist. The present paper presents some of these barriers.

Methods: We performed systematic literature searches and internal European Clinical Research Infrastructure Network (ECRIN) communications during face-to-face meetings and telephone conferences from 2013 to 2017 within the context of the ECRIN Integrating Activity (ECRIN-IA) project.

Evidence-based clinical practice: Overview of threats to the validity of evidence and how to minimise them.

Using the best quality of clinical research evidence is essential for choosing the right treatment for patients. How to identify the best research evidence is, however, difficult. In this narrative review we summarise these threats and describe how to minimise them.

A European multi-language initiative to make the general population aware of independent clinical research: the European Communication on Research Awareness Need project.

Background: The ECRAN (European Communication on Research Awareness Needs) project was initiated in 2012, with support from the European Commission, to improve public knowledge about the importance of independent, multinational, clinical trials in Europe.

Methods: Participants in the ECRAN consortium included clinicians and methodologists directly involved in clinical trials; researchers working in partnership with the public and patients; representatives of patients; and experts in science communication. We searched for, and evaluated, relevant existing materials and developed additional materials and tools, making them freely available under a Creative Commons licence.

Mental health research priorities for Europe.

Mental and brain disorders represent the greatest health burden to Europe-not only for directly affected individuals, but also for their caregivers and the wider society. They incur substantial economic costs through direct (and indirect) health-care and welfare spending, and via productivity losses, all of which substantially affect European development. Funding for research to mitigate these effects lags far behind the cost of mental and brain disorders to society.

Fostering EMA's transparency policy.

The European Medicines Agency has opened a window to access clinical trial data. This is an important step forward which deserves attention, support, and advice from all the stakeholders. Regulatory agencies are the most comprehensive repositories of clinical trial data on drugs and can also promote and develop standard practices for data sharing.

ROAMER: roadmap for mental health research in Europe.

Despite the high impact of mental disorders in society, European mental health research is at a critical situation with a relatively low level of funding, and few advances been achieved during the last decade. The development of coordinated research policies and integrated research networks in mental health is lagging behind other disciplines in Europe, resulting in lower degree of cooperation and scientific impact. To reduce more efficiently the burden of mental disorders in Europe, a concerted new research agenda is necessary.

European Network of Bipolar Research Expert Centre (ENBREC): a network to foster research and promote innovative care.

Bipolar disorders rank as one of the most disabling illnesses in working age adults worldwide. Despite this, the quality of care offered to patients with this disorder is suboptimal, largely due to limitations in our understanding of the pathology. Improving this scenario requires the development of a critical mass of expertise and multicentre collaborative projects.

Typical investigational medicinal products follow relatively uniform regulations in 10 European Clinical Research Infrastructures Network (ECRIN) countries.

Background: In order to facilitate multinational clinical research, regulatory requirements need to become international and harmonised. The EU introduced the Directive 2001/20/EC in 2004, regulating investigational medicinal products in Europe.

Methods: We conducted a survey in order to identify the national regulatory requirements for major categories of clinical research in ten European Clinical Research Infrastructures Network (ECRIN) countries-Austria, Denmark, France, Germany, Hungary, Ireland, Italy, Spain, Sweden, and United Kingdom-covering approximately 70% of the EU population.

Disclosure of investigators' recruitment performance in multicenter clinical trials: a further step for research transparency.

Rafael Dal-Ré and colleagues argue that the recruitment targets and performance of all site investigators in multi-centre clinical trials should be disclosed in trial registration sites before a trial starts, and when it ends.

[ECRIN (European clinical research infrastructures network), a pan-European infrastructure for clinical research].

Clinical research plays a key role both in the development of innovative health products and in the optimisation of medical strategies, leading to evidence-based practice and healthcare cost containment. ECRIN is a distributed ESFRI-roadmap pan-European infrastructure designed to support multinational clinical research, making Europe a single area for clinical studies, taking advantage of its population size to access patients, and unlocking latent scientific providing services to multinational. Servicing of multinational trials started during the preparatory phase, and ECRIN has applied for ERIC status in 2011.

Common definition for categories of clinical research: a prerequisite for a survey on regulatory requirements by the European Clinical Research Infrastructures Network (ECRIN).

Background: Thorough knowledge of the regulatory requirements is a challenging prerequisite for conducting multinational clinical studies in Europe given their complexity and heterogeneity in regulation and perception across the EU member states.

Methods: In order to summarise the current situation in relation to the wide spectrum of clinical research, the European Clinical Research Infrastructures Network (ECRIN) developed a multinational survey in ten European countries. However a lack of common classification framework for major categories of clinical research was identified, and therefore reaching an agreement on a common classification was the initial step in the development of the survey.

Emotional hyper-reactivity in normothymic bipolar patients.

Background: Normothymic states in bipolar disorders are generally considered to be devoid of severe symptoms. However, bipolar patients present subsyndromal symptoms for half of their lives, and often have comorbid psychiatric disorders. If we go beyond the concept of temperamental features, can we identify certain emotional characteristics distinguishing normothymic bipolar patients from normal controls? We previously showed, using self-completed questionnaires, that normothymic bipolar patients display higher levels of emotional lability and intensity than controls.