Operationalization of decentralized clinical trials: The BrUOG354 experience.
Authors: Dizon Don S. , MacLaughlan Shannon Diane , Kim Kang Woo , Wood Roxanne , Hadfield Matthew , Strenger Rochelle , Fenton Mary Anne , Hsu Emily , Lopresti Mary Lorraine , Bandera Christina , Hassinger Faith , Mathews Cara Amanda ,   Brown University Oncology Group
Published: October 2023

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Background: Decentralized clinical trials (DCT) aim to bring a trial’s activities to the patient. However, to date there is little practical experience about conducting them in the therapeutic arena. Due to the COVID-19 pandemic, and in partnership with Bristol Myers Squibb (BMS), we modified our Investigator-Initiated study, BrUOG354 (ClinicalTrials.gov ID: NCT03355976), a phase II trial on the role of Nivolumab and Ipilimumab in extra-renal clear cell carcinoma. This allowed for the shipment of investigational product (IP) to the patient for local administration without trial site activation. Here we report the experience and lessons learned. Methods: The administrative process to facilitate decentralization on BrUOG-354 required FDA guidance, BMS agreement, and Lifespan IRB approval. Brown University Oncology Group (BrUOG) databases were mined for all communications with local sites and providers. We report on enrollment figures per quarter pre- and during/post-pandemic, the number of off-study sites approached, and agreements reached. The reasons for not moving forward at the local site were characterized by two authors (DD, RW). Results: This study was initiated at two Providence health systems initially and activated a third site at the University of Illinois at Chicago in 2021. In total, 46 volunteers were consented to this trial between April 2018 and April 2023, with 16 (34.8%) registered prior to the lockdown in March 2020 and 30 (65.2%) after. Among 34 patients treated at the PI’s institution, seven travelled from out of state for treatment. Two who started treatment pre-lockdown were successfully transitioned so that protocol therapy was administer locally, and both remain on study. Five people were registered during the pandemic and six institutions were approached; three accommodated the request. Reasons provided for not allowing local administration of IP including: unavailability of a research pharmacy (1), blanket institutional prohibition (1) and lack of indemnification language (1). Conclusions: The experience with BrUOG354 exemplifies the potential of DCTs in an oncological setting while simultaneously highlighting barriers to implementation. Therapeutic DCTs are feasible and heightened capacity for future patient-centric trial designs is an exciting prospect. For these to succeed, the ability to conduct study visits by telehealth, especially for out of state residents, is critical. While not originally designed to be decentralized, adopting this approach enabled us to complete enrollment in a rare tumor during the pandemic. By shifting to a patient-centric model, DCTs may improve patient access and options for clinical trials in particular for less common malignancies, while preserving quality of life, addressing financial toxicity, and foster a more diverse trial population. Clinical trial information: NCT03355976 .