The first quarter of 2020 was a period of uncertainty in the timeline of the COVID-19 pandemic, as the pathogenicity and the transmission of the disease remained largely unknown. As the country with the greatest caseload, the majority of clinical trials were based in China. The second highest number of clinical trials were carried out in Iran during this period, followed by the US and Italy. It is therefore apparent that in the early stages of the pandemic, the level of clinical research was dictated by a given country’s caseload. Interestingly, as shown in Figure 1, the overwhelming majority of trials were non-industry-sponsored (88.8%), far outnumbering industry-sponsored trials by 77.6%. These data suggest a predominant number of studies involved repurposing existing off-patent medications as therapeutic agents for COVID-19. With regards to vaccine development, the majority of prospects had a very short window of preclinical development, with Moderna’s mRNA-1273 listed as the first vaccine to enter clinical trials, with the study being initiated just before the end of the first quarter. Phase II trials accounted for the highest number of trials (32.2%) during this period, followed by Phase I (28.1%), Phase IV (19.2%), and Phase III (14.9%).
The second quarter of 2020 represented a period of global rise in cases. The US dominated where the number of new cases were concerned, leading the US to have the greatest number of COVID-19 clinical trials. Iran was in second place, followed by India and Spain. In accordance with the reduction in COVID-19 cases in China, the number of clinical trials initiated decreased almost 6-fold, thereby demonstrating that the capability for clinical research is strongly reduced with a reduction in the relevant patient population. During the second quarter, non-industry-sponsored trials outnumbered industry-sponsored studies by 55.5%, representing a significant increase in the proportion of industry-sponsored trials from 11.2% to 22.5%. The data suggest that many industry sponsors were now targeting a greater number of therapeutic agents in clinical development against COVID-19. Progress was made in the race for a COVID-19 vaccine, with many sponsors announcing Phase I results in which adequate safety profiles were observed. Nonetheless the proportion of Phase I trials fell to 7.4% in the second quarter, with Phase II studies accounting for the greatest proportion (46.7%); Phase III studies also displayed a significant increase in proportion, rising to 36.9%, while Phase IV accounted for 8.9% of trials. The second quarter represented the period with the greatest number of COVID-19 trials being initiated.
The number of trial initiations dropped significantly in the third quarter when compared with the second quarter; this can be attributed to the fact that a greater proportion of trials were already in progress. A record surge in cases was observed worldwide with the US leading, followed by India and Brazil. The US maintained research dominance, marginally outnumbering India with the highest number of trial initiations. Iran dropped to third place, followed by Brazil and the UK. During the third quarter, non-industry-sponsored studies outnumbered industry-sponsored trials by 25.8%, once again highlighting the increased influence of industry sponsors as we transitioned further into the pandemic timeline. Phase II trials again accounted for the largest proportion of studies (48.4%), followed by Phase III (31.8%), Phase I (13.8%), and Phase IV trials (6.0%). Significant vaccine progress was observed in the third quarter with many prospective vaccines demonstrating targeted immune responses, allowing for progression to later-phase studies.
Moving into the fourth quarter, many countries are experiencing second waves of COVID-19, particularly observed in Europe. At present the US leads with the number of trial initiations, followed by India, Canada, Iran, and Spain. Phase II studies remain dominant (46.6%), with Phase III trials (25.4%) narrowly outnumbering Phase I trials (23.9%), and Phase IV trials (4.1%) in fourth place for the third consecutive quarter. The fourth quarter represents a promising period in the pandemic timeline, with a number of sponsors soon issuing the results of their Phase III vaccine studies, thereby presenting a gateway towards approval and the possible initiation of widespread vaccination programs. For the third successive quarter the proportion of industry sponsors has increased, with industry-sponsored trials (53.7%) outnumbering non-industry-sponsored trials (46.3%) for the first time in 2020. This trend demonstrates that the COVID-19 clinical research space is being increasingly influenced by industry sponsors.