Protecting Vulnerable Populations in Clinical Research: Are Children or Adults More At-risk for Non-compliance in Neurologic Protocols?
Matthew Gooden1, Katherine Landry1, Gina Norato1, Sandra Martin1, Henry Roberts1, Lauren Reoma1
1Clinical Trials Unit, NIH/NINDS
Objective:
The objective of this single-center study was to compare non-compliance events in vulnerable populations of children and adults participating in neurologic research protocols.
Background:
Clinical non-compliance with pediatric patients has been well documented, with studies identifying logistical and pharmaceutical issues across countries, notably Saudi Arabia, India, and the United Kingdom. However, additional work is needed to determine the occurrence of pediatric non-compliance in the United States to protect this vulnerable population in neurologic research.
Design/Methods:
A retrospective, cross-sectional cohort study design was used to compare non-compliance across vulnerable populations. Non-compliance was categorized by the type of population enrolled in each study and the non-compliance type, primary category, and cause. Non-compliance rates of the pediatric and adult cohorts were analyzed by calculating comparisons of two rates, incidence rate ratios (IRRs), and 95% confidence intervals.
Results:
Overall, 368 non-compliance events occurred across 2,544 participants. Fourteen events occurred across 25 participants in the pediatric cohort (0.56 events/participant), whereas 354 events occurred across 2,519 participants in the adult cohort (0.14; p<0.001; IRR=3.98 [2.16-6.78]). Minor non-compliance was more likely to occur in the pediatric cohort (0.56 vs. 0.13; p<0.001; IRR=4.37 [2.36-7.44]). Protocol non-compliance (0.32 vs. 0.12; p=0.02; IRR=2.60 [1.11-5.19]), specimen collection (0.20 vs. 0.003; p<0.001; IRR=71.97 [18.01-263.43]), and breach of personally identifiable information (0.04 vs. 0.002; p=0.07; IRR=16.79 [0.37-138.42]) were more likely to occur in the pediatric cohort (pediatric vs. adult, respectively). Lastly, pediatric non-compliance was more likely to be caused by COVID-19 (0.12 vs. 0.07; p=0.38; IRR=1.66 [0.34-4.93]), the research participant (0.24 vs. 0.03; p<0.001; IRR=8.40 [2.98-19.19]) and the study team (0.16 vs. 0.02; p<0.01; IRR=9.16 [2.39-25.16]).
Conclusions:
Pediatric research participants are more likely to experience certain types of non-compliance when compared to adults. The potential for under-reporting is also a factor in this population. Clinical research teams should proactively amend protocols to prevent non-compliance and prioritize safety.