Association of the Coronavirus Disease 2019 (COVID-19) Outbreak With Enrollment in Cancer Clinical Trials

This cohort study investigates how the coronavirus disease 2019 (COVID-19) pandemic is associated with national enrollment in cancer clinical trials.


Introduction
Enrollment in clinical trials is key in advancing new treatments for patients with cancer. Poor accrual can result in trials that fail to complete or generate less timely research findings for patients in need of better therapies. The outbreak of coronavirus disease 2019 (COVID-19) has caused severe disruptions in care for many patients-especially patients with cancer, who are more susceptible to infections because of underlying malignant neoplasms or therapy-in an effort to reduce patient and staff exposure and to preserve resources. Given systemwide changes, some institutions in areas with high rates of COVID-19 have stopped all enrollment in interventional trials, while others have made minor changes. An important question is how the COVID-19 pandemic is associated with national enrollment in cancer clinical trials.

Methods
To address this, we conducted a cohort study to examine initial enrollments in studies conducted by the SWOG Cancer Research Network, a National Cancer Institute-sponsored National Clinical Trials Network group and a member of the National Cancer Institute's Community Oncology Research Program. Enrollments between January 1 and April 25, 2020, were included. Because trial accrual frequently clusters between Monday and Friday, we aggregated enrollments by week. We followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cohort studies. Enrollments were from trials previously approved by an institutional review board; written informed consent was previously obtained for all patients.
Enrollments were compared with the cumulative incidence of confirmed COVID-19 cases in the US. 1 We examined whether changes in enrollment differed by trial type (treatment vs cancer control and prevention), age (<65 vs Ն65 years), sex, and self-reported race and ethnicity. To explore the potential association of regional outbreak severity with enrollment, we examined patterns according to state-level statistics on cases per 100 000 individuals. 2 Logistic regression analyses were used to generate odds ratios, with corresponding Wald χ 2 statistics used to test comparisons. Analyses were conducted in SAS version 9.4 (SAS Institute) and R version 3.4.1 (R Project for Statistical Computing).
Statistical significance was set at α = .05, and all tests were 2-tailed.

Results
Weekly total SWOG enrollments ranged from 125 per week to 150 per week from week 1 (January 1-4) In total, 1870 patients were enrolled (1431 [76.5%] during weeks 1-11 and 439 [23.5%] during weeks 12-17). There were no significant differences in patterns of decreased enrollment by age, race, or ethnicity (Table). Women patients were marginally less likely to be enrolled in weeks 12 to 17 (odds ratio, 0.77; 95% CI, 0.61-0.99; P = .04). Enrollment to cancer control and prevention trials decreased much more than to treatment trials (odds ratio, 0.38; 95% CI, 0.29-0.50; P < .001), potentially reflecting an emphasis on offering beneficial treatment to individual patients. 3 Sites from the states with highest number of COVID-19 cases per 100 000 individuals that composed the upper quintile of The first case of COVID-19 in the US was detected on January 21, 2020. For presentation and estimation purposes, the weekly total for the partial week January 1 to 4 was estimated as the mean daily rate for January 2 to 4 multiplied by 7. The vertical gray bar indicates week 12, when COVID-19 cases in the US increased nearly 10-fold. compared with week 1 to 11 (ie, January 1 to March 14); ORs were estimated among patients with known data.