Journal article
COVID-19 pandemic and enrollment of critically Ill children in randomized clinical trials
Frontiers in pediatrics, Vol.13, 1704390
11/25/2025
DOI: 10.3389/fped.2025.1704390
PMCID: PMC12685906
PMID: 41378199
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.
Details
- Title: Subtitle
- COVID-19 pandemic and enrollment of critically Ill children in randomized clinical trials
- Creators
- Sarah B. KandilDavid Panisello-ManterolaMadhuradhar ChegondiChristine AllenJill M. CholetteMichele KongMatthew PintoHilary SchreiberChristie GlauE. Vincent S. Faustino
- Resource Type
- Journal article
- Publication Details
- Frontiers in pediatrics, Vol.13, 1704390
- DOI
- 10.3389/fped.2025.1704390
- PMID
- 41378199
- PMCID
- PMC12685906
- NLM abbreviation
- Front Pediatr
- ISSN
- 2296-2360
- eISSN
- 2296-2360
- Publisher
- FRONTIERS MEDIA SA
- Grant note
- American Heart AssociationNational Center for Research ResourcesEunice Kennedy Shriver National Institute of Child Health and Human Development
The author(s) declare that financial support was received for the research and/or publication of this article. This publication was made possible in part by Grant Numbers UL1 RR024139, UL1 TR000142 and UL1 TR001863 from the National Center for Research Resources, R21 HD089131 and R01 HD106326 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and 16RNT31180018 from the American Heart Association. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the National Institutes of Health or the American Heart Association.
- Language
- English
- Date published
- 11/25/2025
- Academic Unit
- Stead Family Department of Pediatrics
- Record Identifier
- 9985035036402771
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