Within-Subject Variability and Analytic Imprecision of Insulin-Like Growth Factor Axis and Collagen Markers: Implications for Clinical Diagnosis and Doping Tests
BACKGROUND: The utility of insulin-like growth factor (IGF) axis and collagen markers for a growth hormone (GH) doping test in sport depends on their stability and reproducibility. We sought to determine short-term within-subject variability of these markers in a large cohort of healthy individuals. METHODS: We measured IGF-1, IGF binding protein 3 (IGFBP-3), acid labile subunit (ALS), and the collagen markers N-terminal propeptide of type I procollagen (PINP), C-terminal telopeptide of type I collagen (ICTP), and N-terminal propeptide of type III procollagen (PIIINP) in serum samples obtained on multiple occasions (median 3 per participant) over a 2- to 3-week period from 1103 elite athletes (699 men, 404 women) ages 22.2 (5.2) years [mean (SD)]. We estimated between-subject and within-subject variances by mixed-effects ANOVA. RESULTS: Within-subject variance accounted for 32% to 36% and 4% to 13% of the total variance in IGF markers and collagen markers, respectively. The within-subject CV ranged from 11% to 21% for the IGF axis markers and from 13% to 15% for the collagen markers. The index of individuality for the IGF axis markers was 0.66-0.76, and for the collagen markers, 0.26-0.45. For each marker, individuals with initial extreme measured values tended to regress toward the population mean in subsequent repeated measurements. We developed a Bayesian model to estimate the long-term probable value for each marker. CONCLUSIONS: These results indicate that in healthy individuals the within-subject variability was greater for IGF-1 than for the collagen markers, and that where a single measurement is available, it is possible to estimate the long-term probable value of each of the markers by applying the Bayesian approach. Such an application can increase the reliability and decrease the cost of detecting GH doping.
|Authors||Nguyen, T. V.;Nelson, A. E.;Howe, C. J.;Seibel, M. J.;Baxter, R. C.;Handelsman, D. J.;Kazlauskas, R.;Ho, K. K. :|
|Responsible Garvan Author|
|Publisher Name||CLINICAL CHEMISTRY|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18567697|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/2372|