Search

Background: The new European Medicines Agency (EMA) Clinical Trials Information System (CTIS), based on the Clinical Trials Regulation (CTR EU 536/2014), came into full effect on 31 January 2022 and was intended to provide an easier, more streamlined approach to the registration of clinical trials taking place in Europe. Using the experience gained on the new regulatory framework from three multi-national European clinical research studies of outbreak-prone infectious diseases, this article describes the advantages and shortcomings of the new clinical trial submission procedure. Methods: We report the time to approval, size of the application dossier, and number of requests for information (RFIs) for each study. We also explore the experience of each study within the regulatory framework and its use of CTIS to document the real-world, practical consequences of the system on individual studies. The study assesses the experience of three multi-country studies conducted in Europe working within the EU and non-EU regulatory environments. Results: While the time to regulatory and ethical approval has improved since the implementation of the new regulation, the timelines for approvals are still unacceptably slow, particularly for studies being conducted in the context of an evolving outbreak. Within the new regulatory approval procedure, there is evidence of conflicting application requirements, increased document burden, barriers to submitting important modifications, and debilitating technical hurdles. Conclusions: CTIS promised to lower the administrative bar, but unfortunately this has not been achieved. There are challenges that need to be urgently confronted and addressed for international research collaborators to effectively manage health crises in the future. While the value of multi-national outbreak research is clear, the limitations and delays imposed by the system, which raise challenging ethical questions about the regulation, are prejudicial to all clinical research, especially publicly funded academic studies. This report is relevant to both regulators and clinical researchers. It is hoped that these findings can help improve pan-European clinical trials, especially for the purpose of epidemic preparedness and response. Trial registration: This paper references experiences gained during management of three pan-European trials: EU-SolidAct's Bari-SolidAct (CT No. 2022-500385-99-00 - 15 March 2022) and AXL-SolidAct (CT No. 2022-500363-12-00 - 19 April 2022), and MOSAIC (CT No. 2022-501132-42-00 - 22 June 2022). [ABSTRACT FROM AUTHOR]

Background: Amyotrophic lateral sclerosis (ALS) is a highly debilitating neurodegenerative condition. Despite recent advancements in understanding the molecular mechanisms underlying ALS, there have been no significant improvements in therapeutic options for ALS patients in recent years. Currently, there is no cure for ALS, and the only approved treatment in Europe is riluzole, which has been shown to slow the disease progression and prolong survival by approximately 3 months. Recently, tauroursodeoxycholic acid (TUDCA) has emerged as a promising and effective treatment for neurodegenerative diseases due to its neuroprotective activities. Methods: The ongoing TUDCA-ALS study is a double-blinded, parallel arms, placebo-controlled, randomized multicenter phase III trial with the aim to assess the efficacy and safety of TUDCA as add-on therapy to riluzole in patients with ALS. The primary outcome measure is the treatment response defined as a minimum of 20% improvement in the ALS Functional Rating Scale-Revised (ALSFRS-R) slope during the randomized treatment period (18 months) compared to the lead-in period (3 months). Randomization will be stratified by country. Primary analysis will be conducted based on the intention-to-treat principle through an unadjusted logistic regression model. Patient recruitment commenced on February 22, 2019, and was closed on December 23, 2021. The database will be locked in September 2023. Discussion: This paper provides a comprehensive description of the statistical analysis plan in order to ensure the reproducibility of the analysis and avoid selective reporting of outcomes and data-driven analysis. Sensitivity analyses have been included in the protocol to assess the impact of intercurrent events related to the coronavirus disease 2019. By focusing on clinically meaningful and robust outcomes, this trial aims to determine whether TUDCA can be effective in slowing the disease progression in patients with ALS. Trial registration: ClinicalTrials.gov NCT03800524. Registered on January 11, 2019. [ABSTRACT FROM AUTHOR]

Favoring innovation by making timely medical technology available to people and by securing patients' safety is a challenge. The new European Medical Device Regulation (MDR) will have a central implication in the development of new devices and could affect their innovation and availability, as well as discourage investment in research within Europe. Start-ups and small companies might not be able to cope with the increasing complexity and the required changes of perspective. Health-care institutions are facing an increasing availability of complex technologies, while data on their clinical efficacy and cost-effectiveness are rarely provided. A partnership/collaboration between health-care institutions, academia, and private industries will enhance their own specific interests with the common goal of improving overall health and quality of life. The complexity of the subject combined with the variety of specialists and stakeholders involved requires the implementation, in hospital centers of clinical excellence, of units dedicated to the whole path of the medical device innovation. Stakeholders should quickly provide adequate measures to facilitate the complex medical device innovation path under the more stringent MDR aimed to increase safety and quality of care. [ABSTRACT FROM AUTHOR]

The ongoing COVID‐19 pandemic caused by the SARS‐CoV‐2 coronavirus has affected the health of tens of millions of people worldwide. In particular, in elderly and frail individuals the infection can lead to severe disease and even fatal outcomes. Although the pandemic is primarily a human health crisis its consequences are much broader with a tremendous impact on global economics and social systems. Vaccines are considered the most powerful measure to fight the pandemic and protect people from COVID‐19. Based on the concerted activities of scientists, manufacturers and regulators, the urgent need for effective countermeasures has provoked the development and licensure of novel COVID‐19 vaccines in an unprecedentedly fast and flexible manner within <1 year. To ensure the safety and efficacy of these novel vaccines during the clinical development and the routine use in post‐licensure vaccination campaigns existing regulatory requirements and procedures had to be wisely and carefully adapted to allow for an expedited evaluation without compromising the thoroughness of the regulatory and scientific assessment. In this review, we describe the regulatory procedures, concepts and requirements applied to guide and promote the highly accelerated development and licensure of safe and efficacious COVID‐19 vaccines in Europe. [ABSTRACT FROM AUTHOR]

The management of juvenile idiopathic arthritis (JIA) has improved tremendously in recent years due to the introduction of new drug therapies but remains complex in terms of non-pharmaceutical issues. In order to determine the direction of scientific progress by characterizing the current spectrum of ongoing clinical research in JIA, we analyzed all ongoing studies in the field of JIA—registered in clinicaltrials.gov and clinicaltrialsregister.eu—concerning sponsoring, enrollment, duration, localization, and particularly objectives. The close of the database was 7 January 2021. After identifying double-registered studies, n = 72 went into further analysis. Of these, 61.1% were academia-sponsored and 37.5% were sponsored by the pharma industry. The majority of the studies was of the interventional type (77.8%), while others (22.2%) were observational. The median planned enrollments were 100 participants (interventional studies) and 175 participants (observational studies), respectively. The duration differed remarkably from one month to more than 15 years, with a median of 42.5 months. A total of 61.1% of studies were located in a single country, and 38.9% were in several. Europe and North America clearly dominated the study localizations. The study objectives were DMARDs (56.9%), followed by diagnostics and disease activity measurement (18.1%), and medication other than DMARD (12.5%), besides others. Studies on DMARDs were mainly sponsored by industry, predominantly interventional studies on established and novel biologics, with several on specific issues such as systemic JIA and others. The spectrum of registered studies is currently centered on drug therapy and diagnostics, while other issues in JIA play a subordinated role in current research. Drug development was transferred from adult rheumatology into the JIA population with little innovation for children. Future research should take specific pediatric needs better into account. [ABSTRACT FROM AUTHOR]