In this study, we quantified the impact of the global COVID-19 pandemic on industry-sponsored clinical trial enrollment rates by examining the YOYD in enrollment rate by country and therapeutic area as well as analyzing the correlation between COVID-19 pandemic severity and enrollment rate both during the onset of the pandemic as well as over time. It verified the assumption that, overall, COVID-19 significantly and negatively impacted clinical trial enrollment and provided insights on the differential impacts the pandemic has had at a country level, therapeutic area level, and temporal level.
The impact of the pandemic was most extreme during the spring of 2020 when many countries first faced COVID-19 at a national scale. Given the lack of understanding of the virus in terms of severity, transmission, treatment, and prevention, coupled with a general societal concern, the impact on trial recruitment was part of the much larger lifestyle restrictions put into place by governments. Also, clinical trial sites either elected to not see any new trial participants until more information was known or their resources were diverted to urgent COVID-19-related care and research. While there was a massive decline in overall trial enrollment, some research activity continued such as in oncology where research represents part of cancer care, and is reflected in our results.
We note in our analysis that, overall, the negative relationship between pandemic severity and clinical trial enrollment observed in more recent months has lessened compared to that of the first twelve weeks of the pandemic. This is in large part due to two major trends. First, the international scientific community, through tireless effort and unprecedented scholarly communication across the globe, has learned a great deal about COVID-19 and has created several vaccines to combat the spread of the virus.7 A recent study estimated that vaccines approved for administration outside a clinical trial setting saved 14,4 million lives in 185 countries between December 2020 and December 2021.8 Second, society has grown tolerant and/or fatigued of the various social restrictions deployed almost universally in spring 2020.9 This hypothesis is supported in the analysis of the enrollment impact of the pandemic with a gradual lessening of the impact of the virus on enrollment rates even when infections and deaths were higher than in previous waves. For instance, the United States was impacted by multiple waves of viral variants throughout 2020 and 2021 and those waves had considerably higher death counts and total infections than in spring 2020. However, the decline in enrollment rates in clinical trials, though suppressed during those subsequent waves, was not as severe as in spring 2020. This may reflect also measures taken to adapt clinical research protocols to accommodate the pandemic, implementation of virus control measures,10 or a growing fatigue with viral containment protocols that also hinder business operations, particularly for commercial research sites.
Additionally, the country level differences in pandemic-induced decline in trial enrollment are also observed. There have been many different national level responses to the pandemic, particularly from the perspective of social restrictions such as masking, public gatherings, full community lockdowns, and many others.11 Some countries have deployed clear overarching, low-tolerance policies to aggressively contain the pandemic, whereas others have deployed varied approaches reflecting the state of the pandemic that have been followed by constituents. Others, such as the United States, have left those decisions to individual states and municipalities, creating a heterogeneous response spectrum within a single nation.
Our results are broadly comparable to findings of other reports in the literature. An analysis of 321,218 non–COVID-19–related trials listed on the clinicaltrial.gov database showed that from January 2017 to May 2020, 28,672 (8.9%) trials were stopped (i.e., reported a switch in trial status from “recruiting” to “active and not recruiting”, “completed”, “suspended”, “terminated” or “withdrawn”), revealing that during the initial months of COVID-19, and average of 1,147 trials/month were stopped compared to an average rate of 638 trials/month in the pre-pandemic period, implying a significant slowdown in research activity.12 Another study showed that between February and May 2020, the number of trials activated in the US was just 57% of expected number.13 Another study showed a 60% decrease in the number of launches of phase 1–4 oncology trials during January-May 2020 compared with the pre-pandemic period.14
For future work, we are continuing to monitor the impact of COVID-19 on clinical trial operations and understanding it from long-term perspective. We are also building predictive models that incorporate COVID-19 pandemic severity to forecast enrollment rate, which would allow us to further quantify the impact using model parameters and apply it towards business operations. These observations may assist future researchers with anticipating impacts of pandemics on the conduct of clinical trials on a global scale.