Discussion
stroke, death, venous or arterial thrombosis, ill
MYOCARDIAL INFARCTION, STROKE, EVENT, SECONDARY, EVENTS
This ACTIV-4B trial secondary analysis demonstrates that clinical trial enrollment setting is an important predictor of the composite outcome of hospitalization, venous or arterial thrombosis, stroke, myocardial infarction, or death in patients with clinical stable COVID-19. When adjusted for other risk factors the location of enrollment remains an important predictor of outcomes.The underlying cause of this finding is likely multifactorial. One possible explanation is that patients that are more ill will self-select to an AUEC location out of concern for their health (as opposed to testing remotely) even though at first evaluation they were discharged for care at home. This hypothesis is supported by the observation that the median time to enrollment was shorter among AUEC patients compared with MC patie MC alternatives to AUEC may not have been uniformly available for all ill individuals. While broad awareness of AUECs in a community exists, MC assessment as a potential resource is comparatively novel in clinical research prior to the pandemic. Likewise, MC enrollment was incumbent on screening that occurred at sites that established this novel screening infrastructure. Some of these limitations may be more pronounced in certain areas such as neighborhoods with disproportionally more elderly, or among certain populations (e.g., Blacks and Hispanics). These findings may also highlight the important safety net provided by emergency departments and other AUEC settings in providing access to care or trial opportunities not otherwise readily available to vulnerable patients at elevated risk.We identified phenotypical factors associated with COVID-19 clinical outcome events among patients presenting to an AUEC location or an MC location. These findings have ramifications that can inform future clinical trial design to optimize enrollment equity. While standardized enrollment criteria existed for ACTIV-4B, patients that presented to MC settings and AUEC settings differed. AUEC enrollment patients were more likely to be Black, Hispanic, and older. Some minimal contact COVID-19 clinical trials have had limited success in enrolling targeted numbers of patients [Clinical trials or therapeutic delivery programs designed to reduce hospitalizations or death related to COVID-19 should consider incorporating AUEC enrollment settings into the enrollment and drug delivery design. Indeed, a trial with a comparable outcome to ACTIV-4B would require N = 557 participants per arm to have 80% power to detect a 50% reduction in the outcome with alpha = 0.05 if conducted using AUEC enrollment (outcome event risk 7.9% versus 3.95%) as compared to N = 6,689 participants per arm to detect a similar relative reduction (0.7% versus 0.35%) if conducted using list MC enrollment setting (Fig. 