key: cord-0779395-y1r0h5k4 authors: Arai, Roberto J.; Moniz, Camila M.V.; Chen, André T.C.; Mak, Milena P.; Chammas, Roger; Hoff, Paulo M. title: Managing risks of oncology clinical trials during COVID-19 pandemic date: 2020-08-13 journal: Contemp Clin Trials Commun DOI: 10.1016/j.conctc.2020.100637 sha: 30ea21038b213185bd8bff0435df6bf19e38a0d8 doc_id: 779395 cord_uid: y1r0h5k4 São Paulo city is the epicenter of the Brazilian COVID-19 pandemic. The Instituto do Cancer do Estado de São Paulo is currently conducting 161 multinational sponsored trials plus 116 in house studies in the oncologic population. There are 242 currently active participants and 180 patients in follow-up. The management of the tightly controlled environment of clinical research becomes a challenge, and the Food and Drug Administration set of priority recommendations for patient safety while maintaining study integrity. Fast adaptations are necessary, and actions coalesce to participant protection from COVID-19. We pointed out critical processes for adjustments, and we believe that our experience may help other academic health centers. The COVID-19 pandemic is jostling established processes in academic health centers resulting in a profound reorganization of its clinical operations. The management of resources to prioritize COVID-19 patients raises concerns such as those with chronic diseases, including cancer. Cancer is a potentially life-threatening disease, and, to many patients, particularly in developing and emerging countries, participation in clinical trials represents an alternative means of treatment. The environment to conduct clinical trials requires well-controlled procedures regularly performed in in-person visits. Contrasting, social distancing, and the isolation of infected individuals have long been the primary strategy to fight infectious diseases. The complexities of the pandemics are moving the clinical research toward a high level of uncertainty, and resolute alternatives such as halting research activities are neither feasible nor desirable. The Food and Drug Administration (FDA) published guidance to industry, investigators, and institutional review boards (IRB) on conducting clinical trials during the COVID-19 pandemic 1 . The orientations prioritize participant safety and study J o u r n a l P r e -p r o o f activities could be adapted to achieve the best possible level of patient welfare, otherwise recommending to decision-makers to discontinue study participation if risks outweigh potential benefits. Modern drug clinical trials run in multiple sites worldwide, which have been drastically affected by the COVID-19 pandemic, particularly with couriers' logistics for sample shipping, delivery of investigational products to centers, and to import and export study materials. Withholding or deferring recruitment temporarily during the COVID-19 pandemic could prevent potential risks of candidates to participate in studies that might end up unfinished. It may be necessary to reorganize infrastructure, reestablish logistics, and normalize lockdowns to permit in-person visits. From the participants' perspective, unavoidable non-compliance with study schedules and procedures may be anticipated. Practical obstacles like patient consent withdrawal due to fear of COVID-19 exposure, missed appointments due to lack of transportation, and treatment-toxicity related examination constraints (i.e., shortage of ophthalmologists and otolaryngologists to evaluate immunologic treatment-associated adverse events) require adaptations (Table) . Upon efforts on adjustments, clinical trials should be conducted at a reasonable safety level. In our institution, we interrupted recruitment of all protocols for eight weeks, and 107 days after the 1 st death occurred in March 18 th2 , no dropouts or discontinuation due to COVID-19 were registered. The participants continue to receive experimental treatment during contingency according to protocols, and the primary objectives were successfully assessed. The local site workforce responsible for managing study requirements is multidisciplinary, and an expert team typically requires months of training to achieve an adequate level of experience. The new coronavirus outbreak may cause substantial staff infection and reduction, which may impact the ability to coordinate all corrective and preventive actions. Also, there is a growing possibility of research team reallocation to life-saving pandemic mitigation efforts. Replacement in a clinical trial team is problematic because of specific personnel background and study-related credentials. Leaders should work at different shifts to reduce the risk of simultaneous infection. Virtual meetings and safe desk distances between coworkers may be part of the contingency plan to maintain a minimum organizational structure to coordinate the adjustments. The use of telehealth modalities, including video conferences and The study integrity is of great concern as the overall survival is the most critical endpoint in oncology. A UK report estimates a COVID-19 case-fatality ratio of 28% in cancer patients with symptomatic COVID-19, with mortality increasing with age and • Postponement of the activation of sites that have not yet been initiated until logistics normalization. • Make 4 to 6 months planning for drug supply to included patients. • Consider home delivery of medications, especially oral drugs. • Inform the participants of all study changes and adaptations immediately. 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