The scientific chaos phase of the great pandemic: A longitudinal analysis and systematic review of the first surge of clinical research concerning COVID-19.

Background: Early stages of catastrophes like COVID-19 are often led by chaos and panic. To characterize the initial chaos phase of clinical research in such situations, we analyzed the first surge of more than 1000 clinical trials about the new disease at baseline and after two years follow-up. Our 3 main objectives were: (1) Assessment of spatial and temporal evolution of clinical research of COVID-19 across the globe, (2) Assessment of transparency and quality-trial registration, (3) Assessment of research waste and redundancies.

Methods: By entering the keyword "COVID-19" we screened the International Clinical Trials Registry Platform of the WHO and downloaded the search output when our goal of 1000 trials was reached on the 1st of April 2020. Additionally, we verified the integrity of the downloaded data from the meta registry by comparing the data with each individual registration record on their source register. Also, we conducted a follow-up after two years to track their progress.

Results: (1) The spatial evolution followed the geographical spread of the disease as expected, however, the temporal development suggested that panic was the main driver for clinical research activities. (2) Trial registrations and registers showed a huge lack of transparency by allowing retrospective registrations and not keeping their registration records up to date. Quality of trial registration seems to have improved over the last decade, yet crucial information still was missing. (3) Research waste and redundancies were present as suggested by discontinuation of trials, preventable flaws in study design, and similar but uncoordinated research topics operationally fragmented in isolated silo-structures.

Conclusion: The scientific response mechanism across the globe was intact during the chaos phase. However, supervision, leadership, and accountability are urgently needed to prevent research waste, to ensure effective structure, quality, and validity to ultimately break the "panic-then-forget" cycle in future catastrophes.