V A LeGrys1, T C Moon2, J Laux3, M J Rock4, F Accurso5. 1. Division of Clinical Laboratory Science, University of North Carolina School of Medicine, Chapel Hill, NC, United States. Electronic address: vlegrys@med.unc.edu. 2. Division of Clinical Laboratory Science, University of North Carolina School of Medicine, Chapel Hill, NC, United States. 3. The North Carolina Translational and Clinical Science Institute, University of North Carolina, Chapel Hill, NC, United States. 4. Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States. 5. Department of Pediatrics, University of Colorado Denver School of Medicine, Breathing Institute, Children's Hospital of Colorado, Aurora, CO, United States.
Abstract
BACKGROUND: Using sweat chloride as a biomarker for CFTR modifying drugs requires knowledge of analytical and biological variation. METHODS: 979 sweat chloride concentrations from 128 subjects enrolled in the placebo arm of 2 multicenter, investigational drug trials were analyzed to determine coefficients of variation (CV) as well as reference change value (RCV) and index of individuality (II). RESULTS: For these populations, calculated values for the two studies were: analytical variation (3.9, 4.1%); within-subject variation (4.4, 6.0%); between-subject variation (8.9, 7.0%); RCV (13.7, 17.0%) and II (0.7, 1.0). Sweat chloride variation was not affected by sex, collection site or sample weight; but was slightly affected by age in one of the two studies. CONCLUSION: Through determination of analytical as well as between- and within-subject variation, and with a larger sample size, our data allows improved estimates of the RCV and II, and can contribute to future trials of CFTR modulators and inform the design and interpretation of n of 1 trials in both research and clinical settings.
BACKGROUND: Using sweat chloride as a biomarker for CFTR modifying drugs requires knowledge of analytical and biological variation. METHODS: 979 sweat chloride concentrations from 128 subjects enrolled in the placebo arm of 2 multicenter, investigational drug trials were analyzed to determine coefficients of variation (CV) as well as reference change value (RCV) and index of individuality (II). RESULTS: For these populations, calculated values for the two studies were: analytical variation (3.9, 4.1%); within-subject variation (4.4, 6.0%); between-subject variation (8.9, 7.0%); RCV (13.7, 17.0%) and II (0.7, 1.0). Sweat chloride variation was not affected by sex, collection site or sample weight; but was slightly affected by age in one of the two studies. CONCLUSION: Through determination of analytical as well as between- and within-subject variation, and with a larger sample size, our data allows improved estimates of the RCV and II, and can contribute to future trials of CFTR modulators and inform the design and interpretation of n of 1 trials in both research and clinical settings.
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