Analytical and biological variation in repeated sweat chloride concentrations in clinical trials for CFTR modulator therapy

• Published in: Journal of cystic fibrosis 2018-01, Vol.17 (1), p.43-49
• Main Authors: LeGrys, V.A., Moon, T.C., Laux, J., Rock, M.J., Accurso, F.
• Format: Article
• Language: English
• Subjects: Adult; Analytical variation; Biological variation; Biological Variation, Individual; Chloride Channel Agonists - administration & dosage; Chlorides - analysis; Cystic fibrosis; Cystic Fibrosis - drug therapy; Cystic Fibrosis - genetics; Cystic Fibrosis - metabolism; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Cystic Fibrosis Transmembrane Conductance Regulator - metabolism; Drugs, Investigational - administration & dosage; Female; Humans; Index of individuality; Male; Mutation; Reference change value; Reference Values; Sweat - chemistry; Sweat - metabolism; Sweat chloride
• ISSN: 1569-1993; 1873-5010
• DOI: 10.1016/j.jcf.2017.07.008

Using sweat chloride as a biomarker for CFTR modifying drugs requires knowledge of analytical and biological variation. 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). 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. 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.