title: The development of decision limits for the GH-2000 detection methodology using additional insulin-like growth factor-I and amino-terminal pro-peptide of type III collagen assays.
abstract: The GH-2000 and GH-2004 projects have developed a method for detecting GH misuse based on measuring insulin-like growth factor-I (IGF-I) and the amino-terminal pro-peptide of type III collagen (P-III-NP). The objectives were to analyze more samples from elite athletes to improve the reliability of the decision limit estimates, to evaluate whether the existing decision limits needed revision, and to validate further non-radioisotopic assays for these markers. The study included 998 male and 931 female elite athletes. Blood samples were collected according to World Anti-Doping Agency (WADA) guidelines at various sporting events including the 2011 International Association of Athletics Federations (IAAF) World Athletics Championships in Daegu, South Korea. IGF-I was measured by the Immunotech A15729 IGF-I IRMA, the Immunodiagnostic Systems iSYS IGF-I assay and a recently developed mass spectrometry (LC-MS/MS) method. P-III-NP was measured by the Cisbio RIA-gnost P-III-P, Orion UniQ™ PIIINP RIA and Siemens ADVIA Centaur P-III-NP assays. The GH-2000 score decision limits were developed using existing statistical techniques. Decision limits were determined using a specificity of 99.99% and an allowance for uncertainty because of the finite sample size. The revised Immunotech IGF-I - Orion P-III-NP assay combination decision limit did not change significantly following the addition of the new samples. The new decision limits are applied to currently available non-radioisotopic assays to measure IGF-I and P-III-NP in elite athletes, which should allow wider flexibility to implement the GH-2000 marker test for GH misuse while providing some resilience against manufacturer withdrawal or change of assays.
authors: Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, UK.
authors: Richard I G
authors: RI
authors: Holt
authors: Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, UK.
authors: Walailuck
authors: W
authors: Böhning
authors: Nuffield Division of Clinical Laboratory Sciences, University of Oxford, UK.
authors: Nishan
authors: N
authors: Guha
authors: Department of Pharmacy and Forensic Science, Drug Control Centre, King's College London, UK.
authors: Christiaan
authors: C
authors: Bartlett
authors: Department of Pharmacy and Forensic Science, Drug Control Centre, King's College London, UK.
authors: David A
authors: DA
authors: Cowan
authors: Swiss Laboratory for Doping Analyses, University Center of Legal Medicine, Geneva and Lausanne, Switzerland.
authors: Sylvain
authors: S
authors: Giraud
authors: School of Mathematics, Statistics and Actuarial Science, University of Kent, UK.
authors: E Eryl
authors: EE
authors: Bassett
authors: Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, UK.
authors: Peter H
authors: PH
authors: Sönksen
authors: Southampton Statistical Sciences Research Institute, University of Southampton, UK.
authors: Dankmar
authors: D
authors: Böhning
mesh_terms: D000293:Adolescent; D000328:Adult; D056352:Athletes; D002648:Child; D004300:Doping in Sports; D005260:Female; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D007118:Immunoassay / Q000379:methods; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D057230:Limit of Detection; D008297:Male; D010446:Peptide Fragments / Q000097:blood*; D011347:Procollagen / Q000097:blood*; D015813:Substance Abuse Detection / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods; D055815:Young Adult
chemical_list: D010446:Peptide Fragments; D011347:Procollagen; C041876:procollagen Type III-N-terminal peptide; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I
keywords: amino-terminal pro-peptide of type III collagen (P-III-NP); doping; growth hormone; insulin-like growth factor-I (IGF-I); test