Article Text
Abstract
Objective To investigate agreement between plasma biomarker measurements run in duplicate and explore the precision of statistical modelling approaches using all replicate data vs standard of practice sample means and >20%CV data exclusion.
Design Cohort study.
Setting Canadian high-school and community sport settings.
Participants Healthy youth athletes participating in the SHRed Concussions study (n=149, 48% female, ages 11–17).
Assessment of Risk Factors Previous concussion (Yes/No), age (years), and sex (M/F).
Outcome Measures Plasma GFAP, NF-L, UCH-L1, T-tau, and ptau-181 concentrations (SIMOA;Quanterix) were examined. 95% limits of agreement (95%LOA) between biomarker replicates were assessed using Bland-Altman (B-A) analysis. Three multivariable regression models (α=0.05) were performed to assess estimates of association between independent variables and natural-log (ln) transformed biomarker levels. Model 1 (M1): multi-level model, all replicate data; Model 2 (M2): means of replicates; Model 3 (M3): means of replicates, excluding pairs >20%CV.
Main Results B-A showed 95%LOA in GFAP (-17.74;18.2 pg/mL), UCH-L1 (-13.77;14.82 pg/mL), NF-L (-1.871;1.801 pg/mL), ptau-181 (-0.5314;0.5391 pg/mL) and T-tau (ln-T-tau back-transformed ratio 65.27%;150.03%). Biomarker-specific regression β-estimates differed between M1–3 for each biomarker (largest difference in M3 given data exclusion >20%CV). Age was associated with ln-UCH-L1 in M2 (β=0.0485; 95%CI:0.0006,0.0964). Sex was associated with ln-NF-L [(M1:β=0.1940; 95%CI:0.0135,0.3745); (M2:β=0.1945; 95%CI:0.0105,0.3786)] and ln-GFAP [(M1:β=-0.1676; 95%CI:-0.3037,-0.0315); (M2:β=-0.1668; 95%CI:-0.3066,-0.0270) in M1–2. M1 displayed narrowest 95%CIs (highest estimate precision).
Conclusions Wide 95%LOA in baseline blood biomarkers suggest the mean of sample duplicates may not reflect true population values. Future pediatric sport-related concussion studies may benefit from statistical modelling incorporating all replicate biomarker data to increase estimate accuracy and precision while considering the importance of age and sex.