Association of the Coronavirus Disease 2019 (COVID-19) Outbreak With Enrollment in Cancer Clinical Trials | Infectious Diseases | JAMA Network Open | JAMA Network
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Figure.  Enrollment to National Cancer Institute–Sponsored Trials vs Coronavirus Disease 2019 (COVID-19) Incidence
Enrollment to National Cancer Institute–Sponsored Trials vs Coronavirus Disease 2019 (COVID-19) Incidence

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.

Table.  Changes in Enrollment by Patient and Trial Characteristics and by Spread of COVID-19
Changes in Enrollment by Patient and Trial Characteristics and by Spread of COVID-19
1.
Dong  E, Du  H, Gardner  L.  An interactive web-based dashboard to track COVID-19 in real time.   Lancet Infect Dis. 2020;20(5):533-534. doi:10.1016/S1473-3099(20)30120-1PubMedGoogle ScholarCrossref
2.
GitHub. Data from The New York Times based on reports from state and local health agencies. Accessed April 12, 2020. https://github.com/nytimes/covid-19-data
3.
National Clinical Trial Network Group Chairs. NCTN Group Chairs: cancer trials take backseat to clinical care amid COVID-19 pandemic. The Cancer Letter. Published April 10, 2020. Accessed May 7, 2020. https://cancerletter.com/articles/20200410_1/
4.
National Cancer Institute. Presentations from the 1st virtual joint meeting of NCI Board of Scientific Advisors and National Cancer Advisory Board. April 9, 2020. Accessed April 29, 2020. https://deainfo.nci.nih.gov/advisory/joint/0420/index.htm
5.
US Food and Drug Administration. FDA guidance on conduct of clinical trials of medical products during COVID-19 pandemic. Published March 2020. Accessed April 9, 2020. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/fda-guidance-conduct-clinical-trials-medical-products-during-covid-19-pandemic
6.
National Cancer Institute. Coronavirus guidance. Updated April 1, 2020. Accessed April 9, 2020. https://ctep.cancer.gov/investigatorResources/corona_virus_guidance.htm
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    Research Letter
    Oncology
    June 1, 2020

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

    Author Affiliations
    • 1SWOG Cancer Research Network Statistics and Data Management Center, Fred Hutchinson Cancer Research Center, Seattle, Washington
    • 2SWOG Cancer Research Network Group Chair’s Office, Oregon Health and Science University Knight Cancer Institute, Portland
    • 3Columbia University Medical Center, New York, New York
    JAMA Netw Open. 2020;3(6):e2010651. doi:10.1001/jamanetworkopen.2020.10651
    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 ≥65 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 χ2 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) through week 11 (March 8-14), with a mean (SD) enrollment of 137.0 (9.6) (Figure). Beginning in week 12 (March 15-21), enrollment declined to 109; concurrently, the cumulative COVID-19 cases increased from 2918 to 25 697, a nearly 10-fold increase during 7 days. From week 13 (March 22-28) until the end of the study period, weekly accrual did not exceed 74 patients (mean [SD], 66.0 [7.0]), as cumulative COVID-19 cases neared 1 million.

    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 enrollments in weeks 1 to 11 were only approximately half as likely to enroll patients in weeks 12 to 17 (odds ratio, 0.56; 95% CI, 0.41-0.76; P < .001).

    Discussion

    The COVID-19 pandemic is associated with a notable decrease in enrollment in National Cancer Institute–sponsored cancer clinical trials, especially in areas most affected by COVID-19. The study was limited by its inclusion of enrollment data from only 1 of 4 adult National Cancer Institute network groups; however, the findings are consistent with observed systemwide decreases in accrual.4 In response, the National Cancer Institute6 and the US Food and Drug Administration5 have issued guidance to provide greater flexibility to ensure that patients enrolled in clinical trials are exposed to as little risk as possible during the COVID-19 pandemic. These proactive steps include allowing for remote consent and virtual (ie, telehealth) visits, approaches that may improve the experience of trial participation for patients in the long term. Such measures are vitally important given the critical role government- and industry-sponsored trials play in establishing new oncology treatment options for patients.

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    Article Information

    Accepted for Publication: May 4, 2020.

    Published: June 1, 2020. doi:10.1001/jamanetworkopen.2020.10651

    Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Unger JM et al. JAMA Network Open.

    Corresponding Author: Joseph M. Unger, PhD, SWOG Statistics and Data Management Center, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, M3-C102, PO Box 19024, Seattle, WA 98109-1024 (junger@fredhutch.org).

    Author Contributions: Dr Unger had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: Unger, Hershman.

    Acquisition, analysis, or interpretation of data: All authors.

    Drafting of the manuscript: All authors.

    Critical revision of the manuscript for important intellectual content: Unger, Blanke, Hershman.

    Statistical analysis: Unger.

    Obtained funding: Unger, Blanke.

    Administrative, technical, or material support: Blanke, LeBlanc.

    Supervision: Unger, Blanke.

    Conflict of Interest Disclosures: Dr LeBlanc reported receiving grants from the National Institutes of Health outside the submitted work. No other disclosures were reported.

    Funding/Support: Research reported in this article was supported in part by grant 5UG1CA189974 from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health (Drs Blanke and Hershman); grants U10CA180888 and U10CA180819 from the National Cancer Institute, National Institutes of Health (Drs Blanke and Leblanc, respectively); and in part by The Hope Foundation for Cancer Research in support of infrastructure, data analysis, and trial design within the SWOG Cancer Research Network, at the SWOG Statistics and Data management Center (Dr Unger).

    Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

    Additional Contributions: We wish to recognize all the SWOG researchers and investigators on the front lines of patient care. In addition, the authors wish to thank SWOG staff members Cathy Rankin, MS, for development of coronavirus disease 2019–related data on SWOG trials and Dana Sparks, MAT, for overseeing SWOG protocol changes and memos related to coronavirus disease 2019. They were compensated for their time.

    References
    1.
    Dong  E, Du  H, Gardner  L.  An interactive web-based dashboard to track COVID-19 in real time.   Lancet Infect Dis. 2020;20(5):533-534. doi:10.1016/S1473-3099(20)30120-1PubMedGoogle ScholarCrossref
    2.
    GitHub. Data from The New York Times based on reports from state and local health agencies. Accessed April 12, 2020. https://github.com/nytimes/covid-19-data
    3.
    National Clinical Trial Network Group Chairs. NCTN Group Chairs: cancer trials take backseat to clinical care amid COVID-19 pandemic. The Cancer Letter. Published April 10, 2020. Accessed May 7, 2020. https://cancerletter.com/articles/20200410_1/
    4.
    National Cancer Institute. Presentations from the 1st virtual joint meeting of NCI Board of Scientific Advisors and National Cancer Advisory Board. April 9, 2020. Accessed April 29, 2020. https://deainfo.nci.nih.gov/advisory/joint/0420/index.htm
    5.
    US Food and Drug Administration. FDA guidance on conduct of clinical trials of medical products during COVID-19 pandemic. Published March 2020. Accessed April 9, 2020. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/fda-guidance-conduct-clinical-trials-medical-products-during-covid-19-pandemic
    6.
    National Cancer Institute. Coronavirus guidance. Updated April 1, 2020. Accessed April 9, 2020. https://ctep.cancer.gov/investigatorResources/corona_virus_guidance.htm
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