Athlete’s Biological Passport

Objectives

The objective of this study was to show that it is possible to use indirect markers as sufficient evidence of different types of doping, including blood doping, steroid and hormonal abuse. The biological passport contains all the necessary information useful to make better decisions on the basis on indirect markers, such as the athlete’s physiological characteristics and results of past blood and urine tests making it possible to use the athlete as his or her own reference.

Introduction

Technological advances result in the production of substances with molecular structures that are strictly identical to those of substances produced naturally by the human organism. In such cases, it is impossible to differentiate exogenous and endogenous substances. The use of indirect doping markers offers an interesting alternative to circumvent this problem: instead of focusing on the possible presence of exogenous substances, it looks at modifications of biological parameters induced by doping agents. For example, hemoglobin may be used as an indirect marker of abnormal modifications of erythropoiesis, without necessarily understanding the cause underlying such modification (recombinant erythropoietin doping, blood transfusion doping or growth hormone doping).

Indirect markers have been used in sports for many years, but in an ambiguous manner. For example, the official reason for introducing the hematocrit rule in 1997 was to protect the health of athletes. In practice, however, this rule was a deterrent to the abuse of rEPO. At the same time, infringement of any rule pertaining to an indirect marker does not constitute a violation of the World Anti-Doping Code.

Methods

The results of blood and urine tests were obtained by pooling data from clinical studies and anti-doping tests in order to study the variations in indirect markers that have natural, analytical or artificial causes. The chosen methodology was Bayesian and empirical. Only Bayesian methodology allows one to abandon the notion of causality (doping=effect <-> marker=cause) and to determine whether the observed variations are natural or result from doping.

Results

In this work, we estimated and integrated into a Bayesian network different components of variance of blood doping markers (hemoglobin, OFF-score, ABPS, tHb-mass) and steroid doping makers (T/E). The created network also included models of heterogeneous factors such as the influence of altitude on blood markers on the basis of a model proposed by the WHO. The Bayesian network has been validated and applied to more than 20,000 blood or steroid profiles. A software application, available upon demand, is capable of storing and interpreting an Athlete’s Biological Passport.

Conclusion

Thanks to a number of recent developments, it is possible today to obtain data with sufficient sensitivity and specificity to launch disciplinary action in certain cases on the sole basis of indirect blood markers. The key elements include the introduction of multiparametric markers specific for blood doping, the inclusion of heterogeneous factors such as gender, age, ethnic origin as well as exposure to altitude, reliance on the athlete’s own previous measurements as basal levels, thus using the athlete as his or her own reference, adoption of standardized protocols for blood sample collection and extensive use of external quality control procedures that reduce pre-analytical and analytical variability. The biological passport embodies a shift in the anti-doping paradigm from the archaic hypothesis of unity and perfection to an empirical approach, such as proposed and more easily explained in areas such as DNA-based identification. Currently, there are no scientific or technical obstacles that may prevent the creation of an Athlete’s Biological Passport in any sports discipline. The IGF-1 marker and the multiparametric ASPS marker for steroid doping shall be added to this resource in the near future.

Publications

1. Robinson N., Mangin P., Saugy M., Time and temperature dependant changes in red blood cell analytes used for testing recombinant erythropoietin abuse in sports. Clin. Lab. 50 (2004) 317-23.
2. Robinson N., Schattenberg L., Zorzoli M., Mangin P., Saugy M. Haematological analysis conducted at the departure of the Tour de France 2001. Int J Sports Med. 26(3) (2005) 200-7.
3. Sottas P.-E., Robinson N., Giraud S., Taroni F., Kamber M., Mangin P., Saugy M. Statistical Classification of Abnormal Blood Profiles in Athletes. Int J Biostatistics. 2(1) (2006) 3.
4. Robinson N., Sottas P.E., Mangin P., Saugy M., Bayesian detection of abnormal haematological values to introduce a “no-start” rule for heterogeneous populations of athletes. Haematologica 92 (2007) 1143-1144.
5. Sottas P.E., Baume N., Saudan C., Schweizer C., Kamber M. & Saugy M. Bayesian detection of abnormal values in longitudinal biomarkers with an application to T/E ratio. Biostatistics. (2) (2007) 285-96.
6. Robinson N., Lausanne Blood protocol, Swiss Laboratory for Doping Analyses technical document, 2007.
7. Sottas P.E., Saudan C., Schweizer C., Baume N., Mangin P. & Saugy M. From population- to subject-based limits of T/E ratio to detect testosterone abuse in elite sports. Forensic Science International 174 (2008) 166-72.
8. Sottas P.E., Robinson N., Niggli O., Saugy M., A forensic approach to the interpretation of blood doping markers. Law Probability & Risk, Advance Access published on January 11, 2008, doi:10.1093/lpr/mgm042
9. Sottas P.E., Robinson N., Saugy M., Les marqueurs indirects du dopage sanguin, sous presse.
10. Sottas P.E., Robinson N., Saugy M., The athlete's biological passport and indirect markers of blood doping, in press.

^{Baysian network developed in this study}

^{Athlete's hematological passport result}

Last Update on 07.10.2008