Combined statistical decision limits based on two GH-2000 scores for the detection of growth hormone misuse

TY - JOUR

T1 - Combined statistical decision limits based on two GH-2000 scores for the detection of growth hormone misuse

AU - Liu, Wei

AU - Bretz, Frank

AU - Böhning, Dankmar

AU - Holt, Richard I.G.

AU - Han, Yang

AU - Böhning, Walailuck

AU - Guha, Nishan

AU - Cowan, David A.

N1 - Funding Information: We thank the referees for constructive comments. The authors received no financial support for the research, authorship, and/or publication of this article. Publisher Copyright: © The Author(s) 2022.

PY - 2022/8

Y1 - 2022/8

N2 - The growth hormone-2000 biomarker method, based on the measurements of insulin-like growth factor-I and the amino-terminal pro-peptide of type III collagen, has been developed as a powerful technique for the detection of growth hormone misuse by athletes. Insulin-like growth factor-I and amino-terminal pro-peptide of type III collagen are combined in gender-specific formulas to create the growth hormone-2000 score, which is used to determine whether growth hormone has been administered. To comply with World Anti-Doping Agency regulations, each analyte must be measured by two methods. Insulin-like growth factor-I and amino-terminal pro-peptide of type III collagen can be measured by a number of approved methods, each leading to its own growth hormone-2000 score. Single decision limits for each growth hormone-2000 score have been introduced and developed by Bassett, Erotokritou-Mulligan, Holt, Böhning and their co-authors in a series of papers. These have been incorporated into the guidelines of the World Anti-Doping Agency. A joint decision limit was constructed based on the sample correlation between the two growth hormone-2000 scores generated from an available sample to increase the sensitivity of the biomarker method. This paper takes this idea further into a fully developed statistical approach. It constructs combined decision limits when two growth hormone-2000 scores from different assay combinations are used to decide whether an athlete has been misusing growth hormone. The combined decision limits are directly related to tolerance regions and constructed using a Bayesian approach. It is also shown to have highly satisfactory frequentist properties. The new approach meets the required false-positive rate with a pre-specified level of certainty.

AB - The growth hormone-2000 biomarker method, based on the measurements of insulin-like growth factor-I and the amino-terminal pro-peptide of type III collagen, has been developed as a powerful technique for the detection of growth hormone misuse by athletes. Insulin-like growth factor-I and amino-terminal pro-peptide of type III collagen are combined in gender-specific formulas to create the growth hormone-2000 score, which is used to determine whether growth hormone has been administered. To comply with World Anti-Doping Agency regulations, each analyte must be measured by two methods. Insulin-like growth factor-I and amino-terminal pro-peptide of type III collagen can be measured by a number of approved methods, each leading to its own growth hormone-2000 score. Single decision limits for each growth hormone-2000 score have been introduced and developed by Bassett, Erotokritou-Mulligan, Holt, Böhning and their co-authors in a series of papers. These have been incorporated into the guidelines of the World Anti-Doping Agency. A joint decision limit was constructed based on the sample correlation between the two growth hormone-2000 scores generated from an available sample to increase the sensitivity of the biomarker method. This paper takes this idea further into a fully developed statistical approach. It constructs combined decision limits when two growth hormone-2000 scores from different assay combinations are used to decide whether an athlete has been misusing growth hormone. The combined decision limits are directly related to tolerance regions and constructed using a Bayesian approach. It is also shown to have highly satisfactory frequentist properties. The new approach meets the required false-positive rate with a pre-specified level of certainty.

KW - Bayesian tolerance regions

KW - decision limits

KW - growth hormone misuse detection

KW - growth hormone-2000 scores

KW - tolerance limits

KW - tolerance regions

UR - http://www.scopus.com/inward/record.url?scp=85131042002&partnerID=8YFLogxK

U2 - 10.1177/09622802221093730

DO - 10.1177/09622802221093730

M3 - Article

C2 - 35611962

AN - SCOPUS:85131042002

SN - 0962-2802

VL - 31

SP - 1439

EP - 1448

JO - Statistical Methods in Medical Research

JF - Statistical Methods in Medical Research

IS - 8

ER -