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BRIEF RESEARCH REPORT article

Front. Pediatr.

Sec. Pediatric Critical Care

COVID-19 Pandemic and Enrollment of Critically Ill Children in Randomized Clinical Trials

Provisionally accepted
Sarah B KandilSarah B Kandil1,2*David Jose Panisello-ManterolaDavid Jose Panisello-Manterola3Madhuradhar ChegondiMadhuradhar Chegondi4Christine AllenChristine Allen5Jill Marie CholetteJill Marie Cholette6Michele KongMichele Kong7Matthew PintoMatthew Pinto8Hilary SchreiberHilary Schreiber9Christie GlauChristie Glau10E. Vincent S. FaustinoE. Vincent S. Faustino11
  • 1Department of Pediatrics, Section of Critical Care Medicine, School of Medicine, Yale University, New Haven, United States
  • 2Yale University, New Haven, United States
  • 3Lake Erie College of Osteopathic Medicine, Elmira, United States
  • 4University of Illinois College of Medicine and Children's Hospital of Illinois at OSF Health Care, Peoria, United States
  • 5The University of Oklahoma Health Sciences, Oklahoma City, United States
  • 6University of Rochester Golisano Children's Hospital, Rochester, United States
  • 7The University of Alabama at Birmingham, Birmingham, United States
  • 8Maria Fareri Children's Hospital at Westchester Medical Center, Valhalla, United States
  • 9Medical College of Wisconsin, Milwaukee, United States
  • 10University of Pennsylvania Perelman School of Medicine and Children's Hospital of Philadelphia, Philadelphia, United States
  • 11Yale School of Medicine Department of Pediatrics, New Haven, United States

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ABSTRACT Objective: To evaluate the association of the COVID-19 pandemic with enrollment rates of critically ill children in randomized clinical trials (RCT). We hypothesized that enrollment rates declined due to increased parental refusal. Design: Cross-sectional analysis of 2 multicenter RCTs conducted pre-and post-COVID-19. Setting: A total of 5 centers pre-COVID-19 and 15 centers post-COVID-19 conducting pediatric RCTs on enoxaparin prophylaxis against catheter-associated thrombosis. Patients: Critically ill children <18 years old with newly inserted central venous catheters. Interventions: Randomization to enoxaparin prophylaxis or usual care. Measurements: Enrollment rates and reasons for non-enrollment were analyzed in 622 eligible children: 165 pre-COVID-19 (November 2017–August 2019) and 457 post-COVID-19 (May 2022–August 2024). Main Results: Enrollment rates declined from 30.9% pre-COVID-19 to 18.2% post-COVID-19 (P=0.001). Reasons for non-enrollment differed significantly (P=0.001). Parental unavailability decreased post-COVID-19 (17.7% vs. 34.2%, P<0.001), while research staff unavailability increased (28.6% vs. 15.8%, P=0.006). Overall parental refusal rates remained similar (38.6% pre-COVID-19 vs. 39.6% post-COVID-19, P=0.85). However, among all eligible patients, enrollment failure due to parental refusal increased post-COVID-19 (64.1% vs. 46.3%, P=0.003). Parental refusal inversely correlated with research staff availability (r=- 0.71, P=0.003). Conclusions: The COVID-19 pandemic is associated with lower enrollment rates in RCTs enrolling critically ill children. Increased parental refusal post-pandemic is confounded by reduced research staff availability. Further investigation is needed to assess the role of science denialism and identify strategies to enhance enrollment in RCTs of critically ill children.

Keywords: Pediatrics, Parental Consent, Patient Selection, Thromboprophylaxis, pandemic

Received: 12 Sep 2025; Accepted: 10 Nov 2025.

Copyright: © 2025 Kandil, Panisello-Manterola, Chegondi, Allen, Cholette, Kong, Pinto, Schreiber, Glau and Faustino. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Sarah B Kandil, sarah.kandil@yale.edu

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material