The COVID-19 pandemic and new clinical trial activations

Abstract

Background: The COVID-19 pandemic has caused severe disruptions in care for many patients. A key question is whether the landscape of clinical research has also changed.

Methods: In a retrospective cohort study, we examined the association of the COVID-19 outbreak with new clinical trial activations. Trial data for all interventional and observational oncology, cardiovascular, and mental health studies from January 2015 through September 2020 were obtained from ClinicalTrials.gov . An interrupted time-series analysis with Poisson regression was used.

Results: We examined 62,252 trial activations. During the initial COVID-19 outbreak (February 2020 through May 2020), model-estimated monthly trial activations for US-based studies were only 57% of the expected estimate had the pandemic not occurred (relative risk = 0.57, 95% CI 0.52 to 0.61, p < .001). For non-US-based studies, the impact of the pandemic was less dramatic (relative risk = 0.77, 95% CI 0.73 to 0.82, p < .001), resulting in an overall 27% reduction in the relative risk of new trial activations for US-based trials compared to non-US-based trials (relative risk ratio = 0.73, 95% CI 0.67 to 0.81, p < .001). Although a rebound occurred in the initial reopening phase (June 2020 through September 2020), the rebound was weaker for US-based studies compared to non-US-based studies (relative risk ratio = 0.87, 95% CI 0.80 to 0.95, p < .001).

Conclusions: These findings are consistent with the disproportionate burden of COVID-19 diagnoses and deaths during the initial phase of the pandemic in the USA. Reduced activation of cancer clinical trials will likely slow the pace of clinical research and new drug discovery, with long-term negative consequences for cancer patients. An important question is whether the renewed outbreak period of winter 2020/2021 will have a similarly negative impact on the initiation of new clinical research studies for non-COVID-19 diseases.

Keywords: COVID-19; Cancer clinical trials; Cardiovascular clinical trials; ClinicalTrials.gov; Mental health clinical trials.

Fig. 1

Monthly trial activations over time. a Monthly trial activations for oncology, cardiovascular, and mental-health studies. The gray rectangular shaded area represents the initial pandemic period. The red squares and blue circles show observed non-US-based and US-based (respectively) monthly trial activation totals. The dark red line indicates the Poisson model-fitted (or predicted) non-US-based monthly activation totals; the lighter orange shows the model-based expected (or counterfactual) number of activations had the pandemic not occurred. Similarly, the dark blue line indicates the Poisson regression model-fitted US-based monthly activation totals, and the lighter blue line shows the model-based expected number of activations had the pandemic not occurred. Panel B) Observed monthly trial activations for COVID-19 studies. The red and blue lines show the observed number of trial activations for non-US-based and US-based studies, respectively