Download Journal Club - Clinical Chemistry

Prevalence of Blood Doping in
Samples Collected from Elite Track
and Field Athletes
P.-E. Sottas, N. Robinson, G. Fischetto, G. Dollé,
J.M. Alonso, and M. Saugy
www.clinchem.org/cgi/content/article/57/5/762
May 2011
© Copyright 2011 by the American Association for Clinical Chemistry
Introduction
 Drug testing in elite sports
>World Anti-Doping Agency laboratories statistics:
 2008: 1.08% adverse analytical findings
 2009: 1.11% adverse analytical findings
 Is the prevalence of doping underestimated?
> Because false positives must be avoided, anti-doping tests give
priority to specificity at the expense of sensitivity
> Increasingly sophisticated doping protocols being used to evade
detection by drug tests
> In addition to problem of undetectable substances, drugs designed
specifically to foil drug tests are being produced
© Copyright 2009 by the American Association for Clinical Chemistry
How to estimate the prevalence of doping?
 Questionnaire-based surveys
Individual bias in the assessment of a sensitive attribute
such as doping
> Methods of maintaining confidentiality
Randomized response methods for decreasing evasive answer
bias
> However these methods have never been applied
successfully in world elite athletes
Athletes may still be reluctant to answer truthfully in an
attempt to avoid suspicions directed not only towards
themselves but also towards their sport
> Any more objective alternative?
© Copyright 2009 by the American Association for Clinical Chemistry
Method: Use of biomarkers of doping
 In the clinics
Epidemiological method to characterize a disease has been a
cornerstone method of public health research
> In epidemiology, biomarkers of disease or biomarkers of exposure are
used to provide prevalence measures
Translated to anti-doping
Epidemiological method to characterize the abuse of doping substances
> Prevalence measures based on biomarkers of doping
> Reference cumulative distributions built thanks to data collected in
clinical trials
© Copyright 2009 by the American Association for Clinical Chemistry
Paradigm shift in anti-doping
 From drug tests to biomarkers of doping
The use of biomarkers of doping recently has been formalized in the
so-called Athlete Biological Passport
 Biomarkers of blood doping
Blood doping refers to any method that aims to increase red cell
mass, such as blood transfusion and recombinant EPO (rEPO)
> Blood sampling by sport governing bodies
Some international sport federations introduced the collection of
blood samples and the measurement of red blood cell indices in the
1990's with the aim to limit the abuse of rEPO
© Copyright 2009 by the American Association for Clinical Chemistry
Biomarkers of blood doping
 From a full blood count
Seven red blood cell indices are used to form the
multiparametric marker of blood doping called the Abnormal
Blood Profile Score (ABPS)
> ABPS is a universal marker
Sensitive to rEPO independently of the administration period
> ABPS has proven sensitivity
The higher the sensitivity, the lower the number of tests required
to provide a precise estimate (low sampling error)
> ABPS has good generalization properties
Good internal and external validity (low systematic error)
> ABPS accounts for known effects of heterogenous factors
The marker can be applied to populations stratified according to
sex, age and other heterogenous factors (low bias)
© Copyright 2009 by the American Association for Clinical Chemistry
Blood testing in elite track & field athletes
 Full blood counts since 2001

From 2001 to 2009, the International Association of Athletics
Federations (IAAF) collected 7289 blood samples from 2737
track and field athletes
 Data Collection
 Date of test, venue, sport, type of competition (in-, pre-,
out-of-competition), instrument technology, date of analysis,
sex, birth date and nationality were collected
 Exposure to altitude
 Altitude of the testing location was identified in 3658 tests;
altitude also identified from the athletes’ whereabouts in the
three-week pre-competition profile for the 2005 and 2007
World Championships© Copyright
in Athletics
(3444 entries)
2009 by the American Association for Clinical Chemistry
Results
Table 1. Descriptive statistics on the blood samples collected from elite athletes between 2001 and 2009.
The tested population was highly heterogeneous for many factors (eg 147 nationalities). 79% of samples
collected were from endurance athletes running distances equal to or longer than 800 m. These were
athletes who could benefit from blood doping to enhance their aerobic metabolism. Out-of-competition tests
accounted for approximately a quarter of all the tests (23%).
© Copyright 2009 by the American Association for Clinical Chemistry
Figure 1. Cumulative distribution functions (CDF) of the biomarker ABPS. Black lines: reference CDFs obtained for a
modal population of female athletes; left: assuming no doping; right: assuming doping with microdoses of rEPO. The
difference between the left and right reference CDFs represents the discriminative power of the marker ABPS. Other
lines: empirical CDF obtained from all tests performed on all female athletes of the modal group (green, 1056 samples),
on athletes of country A (red, 67 samples) and on a subgroup that includes athletes from country D (blue,84 samples).
© Copyright 2009 by the American Association for Clinical Chemistry
Prevalence estimates
Table 2. Period prevalence estimates of abnormal blood profiles in elite track and field athletes. n: number
of samples from which the estimates were derived. Prevalence M1: minimal estimates without any
assumptions on the doping method. Prevalence M2: estimates obtained assuming doping with rEPO
microdoses. (): 95% CI estimated by bootstrapping methods, with any negative estimates rounded toward
0%.
© Copyright 2009 by the American Association for Clinical Chemistry
Figure 2. Graphical representation of the blood module of the Athlete Biological Passport for a female
athlete of the modal group. Upper left, hemoglobin (HGB); upper right: stimulation index OFF-score (OFFS);
lower left: ABPS; lower right: reticulocyte percentage (RET%). Blue lines: actual test results (8 tests). Red
lines: individual limits. Colored bars: percentile in the distribution of expected sequences at which falls the
observed sequence. This passport shows variations as expected for a normal physiological condition.
© Copyright 2009 by the American Association for Clinical Chemistry
Figure 3. Graphical representation of the Athlete Hematological Passport for another female athlete of the
modal group (see Figure 2 for details). This passport shows variations and absolute values that are not in
accordance with a normal physiological condition. A closer examination was required to determine whether
the polycythemia presented on several occasions was due to a medical condition or doping. The increased
values were measured before important competitions and most probably implicated a doping behavior.
© Copyright 2009 by the American Association for Clinical Chemistry
Conclusion
 Epidemiological method for doping prevalence
When applied at the population level, biomarkers of blood doping
can be used to derive prevalence estimates of doping
Prevalence estimates depend on nationality
World’s elite athletes are not only heterogenous in physiological
and anthropometric factors but also in their doping behavior
The Athlete Biological Passport
When applied at the individual level, following the concept of
personalized biology, the same biomarkers provide a biological
signature that can be used to detect doping
© Copyright 2009 by the American Association for Clinical Chemistry
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© Copyright 2009 by the American Association for Clinical Chemistry