Evaluating changes in “good safety monitoring” for cancer clinical trial participants during the COVID-19 pandemic.
Authors: Ragavan Meera Vimala , LaLanne Alyssa , Skafel Andrea , Hong Julian C. , Odisho Anobel Y. , Yousefi Sasha , Small Eric Jay , Borno Hala 
Published: September 2021

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Background: Comprehensive and frequent safety monitoring is an essential component of clinical trial conduct to accurately characterize potential toxicities of a study drug and to minimize potential harm to study participants. The COVID-19 pandemic substantially impacted the delivery of cancer care with reduced frequency of overall and in-person visits. We hypothesized that reporting of serious adverse events (SAEs) occurring on clinical trials may have been impacted by these care delivery changes. The current study evaluated pandemic-related changes in the frequency of safety monitoring for cancer patients (pts) enrolled on a clinical trial and identified predictors of SAE reporting before and during the pandemic. Methods: This study included all adult cancer pts enrolled in interventional therapeutic clinical trials at an academic cancer center between 1/1/2019 and 12/30/2020. In this analysis, the "pre-pandemic" period was defined as the time between 1/1/19 and 3/14/20, and the pandemic period between 3/15/20 and the data cutoff date of 12/30/2020. SAE was defined as a grade 3 or grade 4 adverse event (AE) as reported by the trial. Demographic characteristics of pts, visit type (virtual vs in-person), and frequency of SAE reporting were summarized pre-pandemic and during the pandemic. A multivariate logistic regression model was employed to identify predictors of SAE reporting, with the outcome defined as report of at least one SAE from the time pts went on study until the data cutoff date. Covariates included age, gender, race (white vs. non-white), having at least one virtual visit, and enrollment on a trial before versus during the pandemic. Results: This study included 190 pts; 138 (73%) enrolled on trial pre-pandemic and 52 (27%) enrolled during the pandemic. During-pandemic participants were more likely to be older than pts enrolled pre-pandemic, but otherwise the groups were similar in terms of race and gender. Overall, 78 pts (41%) reported an SAE. Among pre-pandemic enrollees, 50% reported at least one SAE, compared to 17% among during-pandemic enrollees. In the multivariate logistic regression model, only enrolling on trial pre-pandemic was associated with a higher likelihood of reporting at least one SAE. Visit type (virtual vs. in-person) was not recorded in over half of during-pandemic patient encounters. Conclusions: There was a significant decline in frequency of SAE reporting during the COVID-19 pandemic. While having at least one virtual visit was not a significant predictor of SAE reporting in the multivariate regression model, our analysis may underrepresent the association of virtual visits and SAE reporting. As the number of virtual visits is expected to stay high post-pandemic, further work is needed to characterize the association of virtual visits and SAE reporting to ensure ongoing adequate safety monitoring for clinical trial patients.