The Athlete Biological Passport: a ‘magic bullet’ for EPO detection? Part 2 of 2

Athlete Biological Passport Procedure Published 07 February 2013 By: Emma Mason

The Athlete Biological Passport: a ‘magic bullet’ for EPO detection? Part 2 of 2

The anti-doping community has taken note of these criticisms (see part 1) and in 2000 WADA approved its operating guidelines for the Athlete Biological Passport (ABP) marking a return to indirect testing methods and a change of analytical focus from urine to blood.

The ABP Procedure

Detection of EPO abuse is determined through analysis of changes in haematological parameters subject to detectable fluctuations following administration. However, the ABP is an altogether more scientifically sophisticated analytical tool than its predecessor, the ‘No Start” rule outlined above. The ABP analyses multiple blood parameters and after an initial blood sample is taken, the athlete’s upper and lower limits are set based on the statistical average of the athlete population. As further tests are conducted the limits are adapted with previous measurements becoming the basal level. Effectively, over time, the limits narrow and the athlete becomes his or her own reference generating a characteristic profile for each athlete. The limits will reach equilibrium and under normal circumstances the athlete’s haematological data will remain within these. These individualised limits allow for natural differences in haematological parameters between athletes, thus overcoming one of the shortcomings of the ‘No Start’ rule. One of the parameters, percentage reticulocytes (RET%) is well known as one of the best indicators of blood doping; EPO administration results in elevation levels of more than 2% while maintenance or ‘washing out’ periods (where the drug is excreted out) the level falls to below that of the athlete’s natural base level. This change in haematological parameters is visible on the ABP by the athlete going outside of their own limits. Consequentially, the OFFs score (a measure of both Haemoglobin values (HGB) and %RET) is specifically used to flag up possible doping activities1 .

ABP profiles are further individualised by the fact that sport specific and medicinal variables that could affect the haematological data have been statistically assessed and formalised. The effects have been documented for differences in training, altitude and medical conditions. By using a Bayesian statistical approach it is possible to remove these factors resulting in a truly individualised profile where an atypical profile can be attributed to a doping offence. On having blood taken, all athletes are required to state additional factors that could affect their data such as altitude training or medical conditions and provide appropriate documentation.

As the ABP analysis is based on a statistical approach to a large quantity of haematological data from empirical testing, an atypical profile should provide strong evidence of a doping offence. In order to substantiate the anti-doping regulator’s case, it has been further suggested that the atypical profile should be accompanied by information surrounding the prevalence of doping within the specific athlete community, for example the sport involved, before a panel of independent experts make an informed decision on guilt or innocence 2. However, it is arguable that to introduce such stereotypes would inevitably encourage a level of bias in analysis of the test results. Thus, it is submitted that this would hinder rather than facilitate the tests credibility.

There are several benefits to the use of the ABP compared to the classical direct detection. If the definition of a fair and effective doping test is one that ensures the risk of false positives are formalised and kept to an absolute minimum, then, it has been argued, these risks must be analysed through statistics3. The introduction of a statistical approach to anti-doping is, therefore, a welcome move. It allows for variation in biological and external factors that have in the past ‘tripped up’ anti-doping scientists and specifically led to a lack of confidence in the scientific and legal credibility of the EPO test. The use of the Bayesian approach4 allows for an application of logic to the relationship of cause and effect: doping activity and change in haematological parameters. The ABP profile has the potential to be a powerful and, more importantly, scientifically and legally credible tool in determination of guilt or innocence.

In addition, the use of blood analysis in place of the traditional urinary analysis has several advantages. Blood analysis is a long established procedure in medicine with modern haematological equipment having high degrees of precision, performance with minimum uncertainty5 . There is an available framework of established standardised analytical procedures that can easily be adapted to the anti-doping requirements thus reducing potential sources of error. The challenge for the anti-doping community will be to ensure that these procedures are universally harmonised. The longitudinal profiling of haematological parameters and the global nature of modern day sporting careers means results will be collected from separate laboratories. However, in order for these data to be credible it is imperative the procedure and measurements at each laboratory are identical and independent of the laboratory that carries them out. A failure to devise and implement identical test conditions would result in unacceptable errors that would increase as further testing at more laboratories was conducted. This would fundamentally undermine the credibility of the ABP.

The current status is that implementation of the ABP is being encouraged by WADA but it is not yet being employed as a stand-alone analytical tool. More specifically, several endurance sports directly affected by the prevalence of EPO abuse, such as cycling and athletics, are running pilot programmes in conjunction with classical methods. The UCI conducted analysis of 20,000 blood samples from 850 cyclists between 2008 and 20096 . The UCI were positive in review believing it to be a major step forwards for the anti-doping movement citing two successful convictions for doping offences through the ABP programme (after further confirmation by the direct detection method). Furthermore, they suggested the mere existence of the passport was acting itself as a deterrent: riders were not able to secure professional contracts if they had an unexplained, atypical profile.

However, the phased introduction of the passport has not been without issue. Problems included an increase in cost and resources to ensure standardised protocols, analytical steps and external quality assessment. External criticism of the ABP so far has included the use of a flawed statistical method in the longitudinal profiling7 that could be corrected by the use of experienced statisticians rather than haematological experts to analyse data8. More worryingly it has been reported that the ABP, like the direct EPO test, is unable to detect micro dosing9 . The research showed that micro dosing with EPO caused a simultaneous significant increase in blood volume. Thus, as the ABP measures red blood cell concentration rather than the amount of red blood cells the body’s biological response is able to disguise changes in the parameters that would normally indicate EPO abuse and prompt further investigation. Michael Ashenden, the doping expert who conducted the research, and who had been acting as an independent reviewer for blood profiles in cycling, has recently resigned from the regulatory body responsible for management of the ABP10 The Athlete Passport Management Unit. Ashenden cited a contractual clause barring him from discussing the passport in public during his role (and up to eight years after) as the reason for his resignation. He believes transparency is essential to gain confidence in the ABP and education of the media and public is a key way in which to do this. It is clear restriction of that freedom is counterintuitive: it suggests the anti-doping community have something to hide and prevents important discussion on ways in which the passport could be improved thus hindering further development of the test. Finally, critics of the ABP have argued that a doping conviction based on the profile alone will not be legally enforceable until the science (both statistical and biochemical) on which it is based is no longer refutable11 . This last point is specifically important in ensuring not only the operational future of the ABP but in safeguarding the athletes themselves and the reputation of the anti-doping movement as a whole. In other words, if the ABP is to be an effective test for EPO it must be based on sound science and capable of detecting abuse: only then can it provide athletes and the public with the confidence that EPO abusers will be caught.

 

Conclusion

EPO has been problematic for anti-doping scientists to detect since the drug was developed over two decades ago. The physiological advantages it affords and the obstacles to detection are ample explanation for its widespread use by athletes seeking to gain an unfair advantage. Despite the extensive efforts of the anti-doping movement and the level of scientific sophistication employed, the classical direct detection method has encountered many difficulties and confidence in its ability is low. On the other hand, the ABP seems to have captured the confidence of the athlete community. However, in order to maintain this, the anti-doping community should heed both the successes and failures from the pilot programmes and use them to further develop and improve the tool prior to mandating use. By doing so, the anti-doping community may avoid the public controversies and forced adaptations that have plagued the current EPO test, thus providing an altogether more trusted and effective analytical test for EPO that would prevent another Lance Armstrong style revelation in future.

 

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Author

Emma Mason

Emma Mason

Emma is a trainee solicitor in Squire Patton Boggs’ sports litigation department who has completed seats in corporate, international dispute resolution and a secondment to Chelsea Football Club. During her traineeship Emma has, from a sporting perspective, assisted with the sale of a Championship football club and the provision of advice to various International Federations and Premier League football clubs.