123 - COVID19 and Enrollment of Critically Ill Children in a Clinical Trial

Publication Number: 123.4236

Sarah B.. Kandil, Yale School of Medicine, New Haven, CT, United States; David J. Panisello-Manterola, Yale-New Haven Children's Hospital, Elmira, NY, United States; Madhuradhar Chegondi, University of Illinois College of Medicine, Peoria, IL, United States; Christine Allen, Oklahoma Childrens Hospital at OU Health, Oklahoma City, OK, United States; Jill M. Cholette, Golisano Children's Hospital at The University of Rochester Medical Center, Rochester, NY, United States; Michele Kong, University of Alabama School of Medicine, Birmingham, AL, United States; Matthew Pinto, Maria Fareri Children's Hospital at Westchester Medical Center, Valhalla, NY, United States; E Vincent Faustino, Yale School of Medicine, New Haven, CT, United States; Christie L. Glau, Perelman School of Medicine at the University of Pennsylvania, Newtown Square, PA, United States; Hilary Schreiber, Children's Hospital of Wisconsin, Milwaukee, WI, United States

Background: Enrollment of critically ill children in randomized clinical trials (RCT) is challenging. Rising in prevalence during the coronavirus-19 (COVID19) pandemic, science denialism has further complicated enrollment.

Objective: We hypothesized that the COVID19 pandemic is associated with lower enrollment rates of critically ill children in RCTs due to increased parental refusal.

Design/Methods: We enrolled in 5 centers a phase 2b RCT of early prophylaxis against catheter-associated thrombosis in critically ill children from November 2017 to August 2019 (pre-COVID19). We randomized critically ill children < 18 years old with a newly inserted central venous catheter to enoxaparin prophylaxis or usual care. Based on findings from this RCT, enrollment for a multicenter (15 centers) phase 2/3 RCT with comparable eligibility criteria and study design began in May 2022 (post-COVID19). In this study, we analyzed eligible children from the pre-COVID19 RCT and up to August 2024 from the post-COVID19 RCT. Enrollment rates and reasons for failure to enroll were analyzed with descriptive statistics and Chi-Squared analysis.

Results: We analyzed 622 eligible children, of whom 165 (26.5%) were pre-COVID19 and 457 (73.5%) were post-COVID19. Enrollment rates were 30.9% pre-COVID19 and 18.2% post-COVID19 (P=0.001). Distribution of reasons for not enrolling eligible children were different pre- and post-COVID19 (P=0.001) (Figure 1). Parents not available was proportionally lower post-COVID19 (17.7% vs 34.2% pre-COVID19, P< 0.001), while research staff not available was higher post-COVID19 (28.6% vs 15.8% pre-COVID19, P=0.006). Parental refusal was comparable (38.6% pre-COVID19 vs 39.6% post-COVID19, P=0.85). However, the percentage of parental refusal per hospital was inversely correlated with the percentage of research staff not available (correlation coefficient: –0.71, P=0.003) (Figure 2). Among all eligible patients, enrollment failure due to the percentage of parental refusal was higher post-COVID19 at 64.1% of 231 children versus 46.3% of 95 children pre-COVID19 (P=0.003) (Figure 3).

Conclusion(s): The COVID19 pandemic is associated with lower enrollment rates of critically ill children in RCTs. In children approached for RCT enrollment, the percentage of parental refusal was more frequent post-COVID19. This is confounded by higher rates of research staff not available post-COVID19. Further studies should explore the impact of science denialism in parental refusal to identify interventions and increase enrollment of critically ill children in RCTs.

Figure 1
Stacked bar chart of reasons for not enrolling eligible children by enrollment period. The distribution of reasons for not enrolling these children was different pre- and post-COVID19.

Figure 2
Scatterplot of parental refusal and research staff not available. The percentage of parental refusal per hospital was inversely correlated with the percentage of unavailability of research staff.

Figure 3
Stacked bar chart of outcomes of parents approached for enrollment. Among these children, the percentage of parental refusal was higher post-COVID19 than pre-COVID19.