key: cord-0955327-tq65gs0f
authors: Yeboa, Debra Nana; Akinfenwa, Chidinma Anakwenze; Nguyen, Jonathan; Amaya, Diana; de Gracia, Beth; Ning, Matthew; Cox, Victoria; De, Brian; Smith, Benjamin D.; Lin, Lili; Beddar, Sam; Hoang, Hanh; Koong, Albert; Liao, Zhongxing
title: Effectively Conducting Oncology Clinical Trials during the COVID-19 Pandemic
date: 2021-03-03
journal: Adv Radiat Oncol
DOI: 10.1016/j.adro.2021.100676
sha: 56f65ec8d20c53a0e6292cd50a6be0ed7a5efa63
doc_id: 955327
cord_uid: tq65gs0f

INTRODUCTION: Clinical trial enrollment has declined globally due to the COVID-19 pandemic. This underscores the importance of structured methods to continue critical medical research safely and efficiently. METHODS: We report the impact of a phased trial reopening strategy, remote research staffing, and telemedicine on cancer trial enrollment at one of the largest Radiation Oncology academic cancer centers. In Phase 1, trials investigating definitive therapeutic benefit were opened, followed by trials not increasing patient exposure or pulmonary toxicity risk in Phase 2. During Phase 2.5, multicenter trials reopened and limited research staff were allowed on-site. RESULTS: Despite initial enrollment declines during the early pandemic, the percentage of new patients enrolling in clinical trials from March to August 2020 was 8.8%, and represented an 10.5% relative increase from 2019. Monthly accrual enrollment from March to August 2019 ranged from 42-71 compared to enrollment during COVID-19 from 23-73 patients (p<0.001). CONCLUSIONS: Through a phased approach to trial reopening and adaptive techniques, the Division of Radiation Oncology maintained cancer trial accrual during the COVID-19 pandemic. The experience may help centers maintain accrual, preserve clinical trial integrity, and minimize risk to patients and staff.

In response to the COVID-19 pandemic, the US Food and Drug Administration (FDA) provided guidelines to safely and efficiently continue critical medical research.(1) It included nonbinding recommendations for resource allocation, remote monitoring and consenting, and new methods for clinical outcome assessments. At one of the world's largest cancer centers, the Division of Radiation Oncology (RO) conducts over 100 clinical protocols. We analyzed how a phased approach to trial reopening, remote coordination of research staff, and telemedicine allowed for continuing cancer clinical trials.

In March, we paused certain clinical trials, required research staff to work remotely, and planned a multi-phase approach for reopening trials (Figure 1, Figure 2 ). We adopted institutional policies to mitigate the risk of COVID-19 exposure, including limiting laboratory and clinical personnel interaction. For Phase 1, we selected therapeutic protocols that met specific criteria, such as potential for lifesaving, therapeutic, or clinical benefit while minimizing correlative procedures. We assessed if trials increased patient visits beyond standard-of-care or if investigational agents increased immunosuppression or pulmonary toxicity risks.

During Phase 2 in May 2020, we considered reopening trials that would not increase blood 

Forty-four, 139, and 73 patients enrolled on therapeutic trials during Phase 1, Phase 2, and Phase 2.5, respectively, which corresponds to 1.2, 2.4, and 2.5 patients enrolled per day in each phase. Monthly accrual pre-COVID-19 from September 2019 to February 2020 ranged from 50-75 patients, in contrast to enrollment during COVID-19 after March 2020 ranging from 23-73 patients (Table 1, Figure 3 ). Enrollment from FY19 March to August ranged from 42-71, which is statistically different from the same months during the COVID-19 pandemic in FY20 (p<0.001). Enrollment as a percentage of patients treated in the department pre-pandemic in FY20 ranged from 7.9% to 10.6% before March, though dropping to 4.9% in April 2020 and rebounding to 11.3% in July with increased telemedicine resources. When evaluating changes J o u r n a l P r e -p r o o f and 45.7% [FY20 N=73/647, 11.3% vs FY19 N=55/710, 7.7%] in June and July 2020 compared to 2019. Overall, the 6-month percent enrollment during COVID-19 was 8.8%, reflecting a relative increase of 10.5% from FY19 to FY20. The pandemic also impacted our geographic catchment area for RO patient enrollment across the institution, with a greater proportion of enrollees living in Texas in FY20 (Table 2 ).

Modeling institutional guidance, our Division instituted a phased approach to maintain trial accrual by first prioritizing therapeutic trials with potential clinical benefit over standard-of-care. It was followed by reopening trials that could be conducted safely with minimal operational logistics. Adaptive techniques in remote staffing and telemedicine resulted in enrollment being (11, 12) Other approaches suggested stratifying patients by degree of risk, especially if older or with comorbidities, which reflect some of our strategies. (13, 14) With only 8% of all cancer patients enrolling on clinical trials,(5) more virtual trials could improve enrollment while also potentially shifting geographic demographics as seen at our center. As we moved towards regional marketing during the pandemic, we saw increases in percentages of instate participants. In a survey of US Cancer Centers of Excellence with above-average recruitment of ethnic minority groups such as our center, increasing local community engagement through strategic initiatives could be an important component for increasing diversity with virtual trials in the future. (15) Observation data has limitations and there may be unmeasured confounding factors contributing to enrollment patterns during COVID. For instance, several institutional policies and J o u r n a l P r e -p r o o f 6 changes in clinic procedures were necessary to adjust to the pandemic. However, we took into account how relative changes in clinic volume could impact enrollment.

Our departments were able to increase clinical trial enrollment with a detailed stepwise approach that prioritized patient safety and telemedicine techniques. Using techniques to preserve integrity of oncology trials in the COVID-19 era offers hope for cancer patients while advancing academic science. J o u r n a l P r e -p r o o f 1.8% a This number reflects unique patient enrollments of Radiation Oncology patients that were enrolled on institution-wide trials b Percentages do not sum to 100% as these represent enrollment numbers for the most highly represented states

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