Perpetual observational studies: new strategies to support efficient implementation of observational studies and randomized trials in infectious diseases
Hassoun-Kheir N, van Werkhoven CH, Dunning J, Jaenisch T, van Beek J, Bielicki J, Butler CC, Francois B, Harbarth S, Hernandez Padilla AC, Horby P, Koopmans M, Lee J, Rodriguez-Baño J, Tacconelli E, Themistocleous Y, van der Velden AW, Bonten M, Goossens H, de Kraker MEA
Clin Microbiol Infect
].Emerging infectious diseases are a growing threat, through population growth, increased trade and travel, urbanization, deforestation, and climate change []. Clinical research in response to emerging infectious diseases is challenging; selecting and contracting the appropriate study sites for a trial is time consuming, and often too few patients can be timely recruited to acquire high-quality evidence about the best treatment strategies []. In 2014, the EU-funded PREPARE project (Platform foR European Preparedness Against (Re-)emerging Epidemics) was initiated to rapidly respond to severe infectious diseases outbreaks. It initiated two adaptive platform trials, the REMAP-CAP [] and the ALIC4E trial [], determining the effectiveness of multiple treatment strategies for a single disease. The REMAP-CAP trial was designed for a pandemic of severe community-acquired pneumonia and expanded globally during the COVID-19 pandemic. It has already delivered 10 important conclusions for better treatment of COVID-19 [
].Antimicrobial resistance (AMR), on the other hand, is a more silent pandemic, which further augments the burden of infectious diseases. Development of new antibacterial agents has slowed, due to a combination of low return on investment and challenging clinical trial conditions []. Since the 2000s, national and global efforts have been initiated to promote antibiotic development, including the setup of public–private partnerships, like COMBACTE (Combatting Bacterial Resistance in Europe), funded by the EU's Innovative Medicines Initiative. Since 2013, COMBACTE has focused on rapid and efficient development of new AMR prevention and treatment strategies, through site selection streamlining, real world data collection for patient enrichment and pathogen prioritization [], and improvement of clinical trial efficiency through innovative methodological and statistical approaches [
A clinical research network applying different innovative concepts could enhance research efficiency to address both the growing threat of (re-)emerging infectious diseases and the increasing burden of AMR. Therefore, the academic partners from PREPARE, COMBACTE, and other EU-funded collaborative networks (see Acknowledgements) combined their strengths to establish the European Clinical Research Alliance on Infectious Diseases (Ecraid) Foundation in January 2022—a clinical research network that aims to efficiently generate rigorous evidence to improve the diagnosis, prevention, and treatment of infections in Europe through innovative solutions. Here we discuss the advantages and challenges of the implementation of Perpetual Observational Studies (POS).