Within-subject variability and analytic imprecision of insulinlike growth factor axis and collagen markers: implications for clinical diagnosis and doping tests.
BACKGROUND
The utility of insulinlike 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-I, 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-I 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.
Nguyen
Tuan V
TV
Garvan Institute of Medical Research and Department of Endocrinology, Sydney, Australia.
Nelson
Anne E
AE
Howe
Christopher J
CJ
Seibel
Markus J
MJ
Baxter
Robert C
RC
Handelsman
David J
DJ
Kazlauskas
Ray
R
Ho
Ken K
KK
D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D019411:Clinical Laboratory Techniques / Q000379:methods / Q000592:standards; D015331:Cohort Studies; D003094:Collagen / Q000032:analysis* / Q000097:blood; D004300:Doping in Sports / Q000517:prevention & control*; D005260:Female; D013006:Growth Hormone / Q000097:blood*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008297:Male; D012680:Sensitivity and Specificity; D013177:Sports / Q000592:standards*; D015813:Substance Abuse Detection / Q000379:methods / Q000592:standards
D015415:Biomarkers; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D003094:Collagen