ABSTRACT
Background We have followed the COVID-19 clinical trial research agenda from the beginning using the COVID-evidence.org platform. Now, two years after the COVID-19 pandemic started, our aim was to re-examine this research agenda with the latest data to provide a global perspective on the research landscape with a focus on Germany. Methods We reviewed and updated previously published data on the COVID-19 clinical research agenda as of 28February 2022 focusing on randomized trials. We used the COVID-evidence.org platform including registry entries from ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform as well as publications from the Living OVerview of Evidence platform for COVID-19 (L·OVE). Results Two years on from the pandemic outbreak, there were 4,673 registered trials. The majority of these trials have remained small with a median of 120 planned participants (IQR 60-320). In the first hundred days of the pandemic most of them (50 %) had been registered in China. More than two years later, the five countries with the most registered trials (alone or within a framework of international collaborations) were the USA (825 trials;18 %), Iran (619 trials;13 %), India (566 trials;12 %), China (353 trials;8 %), and Spain (309 trials;7 %). Only 119 trials were reported to have a study site in Germany (2.5 % of the registered trials). Of the 4,673 trials registered, 15 % (694 trials) had published their results by February 2022. The clinical research agenda has been marked by both successes, such as the large RECOVERY trial providing evidence on 10 treatments for COVID-19 including over 45,000 patients as of February 2022, and failures: worldwide only 57 randomized trials have been registered over two years that aimed to assess non-pharmaceutical interventions (e.g., face mask policies and lockdown measures) to prevent COVID-19, and only 11 of them had published results informing decisions that have an impact on the life of billions of people worldwide. Conclusions The COVID-19 clinical research agenda has highlighted the substantial effort of the research community but also the challenges of the clinical research ecosystem. Most importantly, it has shed light on the ability to circumvent traditional barriers and to make trials more useful even under extraordinary conditions. The time to learn our lessons and apply them is now, and the time to demonstrate how we have improved the system is before the next pandemic.