Patient hesitancy in perioperative clinical trial enrollment during the COVID-19 pandemic

PLOS ONE RESEARCH ARTICLE Patient hesitancy in perioperative clinical trial enrollment during the COVID-19 pandemic Josue D. Chirinos ID1, Isabella S. Turco ID2, Raffaele Di Fenza ID1,2, Stefano Gianni1,2, Grant M. Larson ID2,3, Joseph F. Swingle4, Oluwaseun Akeju ID1,2☯, Lorenzo Berra ID1,2,5☯* 1 Harvard Medical School, Boston, Massachusetts, United States of America, 2 Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America, 3 Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America, 4 Department of Sociology, Wellesley College, Wellesley, Massachusetts, United States of America, 5 Respiratory Care Services, Massachusetts General Hospital, Boston, Massachusetts, United States of America a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 ☯ These authors contributed equally to this work. * Abstract OPEN ACCESS Citation: Chirinos JD, Turco IS, Di Fenza R, Gianni S, Larson GM, Swingle JF, et al. (2023) Patient hesitancy in perioperative clinical trial enrollment during the COVID-19 pandemic. PLoS ONE 18(1): e0279643. https://doi.org/10.1371/journal. pone.0279643 Editor: Seth Kwabena Amponsah, University of Ghana Medical Centre, GHANA Received: June 20, 2022 Accepted: December 12, 2022 Published: January 17, 2023 Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. The editorial history of this article is available here: https://doi.org/10.1371/journal.pone.0279643 Copyright: © 2023 Chirinos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The COVID-19 pandemic has caused tremendous disruptions to non-COVID-19 clinical research. However, there has been little investigation on how patients themselves have responded to clinical trial recruitment during the COVID-19 pandemic. To investigate the effect of the COVID-19 pandemic on rates of patient consent to enrollment into non-COVID19 clinical trials, we carried out a cross-sectional study using data from the Nitric Oxide/Acute Kidney Injury (NO/AKI) and Minimizing ICU Neurological Dysfunction with Dexmedetomidine-Induced Sleep (MINDDS) trials. All patients eligible for the NO/AKI or MINDDS trials who came to the hospital for cardiac surgery and were approached to gain consent to enrollment were included in the current study. We defined “Before COVID-19” as the time between the start of the relevant clinical trial and the date when efforts toward that clinical trial were deescalated by the hospital due to COVID-19. We defined “During COVID-19” as the time between trial de-escalation and trial completion. 5,015 patients were screened for eligibility. 3,851 were excluded, and 1,434 were approached to gain consent to enrollment. The rate of consent to enrollment was 64% in the “Before COVID-19” group and 45% in the “During COVID-19” group (n = 1,334, P<0.001) (RR = 0.70, 95% CI 0.62 to 0.80, P<0.001). Thus, we found that rates of consent to enrollment into the NO/AKI and MINDDS trials dropped significantly with the onset of the COVID-19 pandemic. Patient demographic and socioeconomic status data collected from electronic medical records and patient survey data did not shed light on possible explanations for this observed drop, indicating that there were likely other factors at play that were not directly measured in the current study. Increased patient hesitancy to enroll in clinical trials can have detrimental effects on clinical science, patient health, and patient healthcare experience, so understanding and addressing this issue during the COVID-19 pandemic is crucial. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. PLOS ONE | https://doi.org/10.1371/journal.pone.0279643 January 17, 2023 1 / 16 PLOS ONE Funding: LB receives salary support from K23 HL128882/NHLBI NIH as principal investigator for his work on hemolysis and nitric oxide. LB receives technologies and devices from Inhaled Nitric Oxide (NO) Therapeutics LLC, Masimo Corp. This study was supported through LB by the Reginald Jenney Endowment Chair at Harvard Medical School, by Sundry Funds at Massachusetts General Hospital, and by laboratory funds of the Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine at Massachusetts General Hospital. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: LB has filed a patent application on June 7, 2021 for NO delivery in COVID-19 disease: PCT application number: PCT/ US2021/036269. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Patient hesitancy in perioperative clinical trial enrollment during the COVID-19 pandemic Introduction Since the World Health Organization (WHO) announced the rise of a novel coronavirusrelated pneumonia in Wuhan, China on January 9, 2020 [1], the coronavirus disease 2019 (COVID-19) pandemic has dramatically altered the lives of virtually every human on the planet. According to the WHO, as of November 2022, there have been over 639 million confirmed cases of COVID-19 worldwide and over 6.6 million associated deaths [2]. Additionally, the COVID-19 pandemic has imposed substantial economic burdens, with early estimates in the tens of trillions of dollars in the United States alone [3]. The COVID-19 pandemic has also caused tremendous disruptions to non-COVID-19 clinical research. An April 2020 study showed that of over 1,000 clinical trial site personnel surveyed, 69% reported that the COVID-19 pandemic had affected their ability to conduct ongoing clinical trials and 78% reported that it had affected their ability to initiate new clinical trials [4–6]. Additionally, studies have reported decreases in clinical trial patient recruitment [4]. In this setting, there was a concomitant global decline in patient enrollment during the COVID-19 pandemic, with a 59% drop from the pre-COVID-19 baseline by the end of April 2020 [7]. Clinical trial disruptions and reduced patient enrollments have detrimental effects on the advancement of clinical science. Additionally, patients enrolled in clinical trials often receive new cutting-edge treatments, have more frequent health check-ups and medical care, and gain access to information about disease support groups and resources [8]. Thus, clinical trial disruptions and reduced patient enrollments into clinical trials can also (...truncated)