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You’re 1 in 1,000 Baby: Understanding the Bio-Passport OFF-Score

October 12, 2013
Trends in Reticulocyte Percent (R%), R-count, and OFF-score for 3 blood samples taken over 10 days of racing for 253 riders participating in the 2010 and 2012 GiroBio, http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0063092

Figure 1: Trends in Reticulocyte Percent (R%), R-count, and OFF-score for 3 blood samples taken over 10 days of racing for 253 riders participating in the 2010 and 2012 GiroBio, http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0063092

Disclaimer: I am not a physician, hematologist, anti-doping expert, or even a veterinarian.  I am just a coach and athlete who has a passion for data analysis, visualization and clean and fair sporting.

The “Athlete’s Biological Passport” (ABP) is used in cycling to detect changes in an athlete’s balance of haemotological parameters that might be indicative of doping. The passport if a set of blood values and associated metrics that attempts to describe an athlete’s “normal” or “equilibrium” point, a way of separating natural variations due to genetics, environment and training stimuli from the variations that result from prohibited pharmacological stimuli. It is a complex topic, with the experts in interpreting the passport often expressing their beliefs in terms of probabilities, likelihoods, and ultimately, taking very conservative approaches to the responsibility that they have: their judgement can ultimately be a substitute for a “positive” or “negative” doping charge. One feature of the ABP is what’s known as the “OFF-Score” – a score which has an upper and lower range of “normal” values, in other words, a too high or too low OFF-score is considered to be indicative of doping. Though the experts reiterate that the OFF-score is merely one part of their ABP assessment, perhaps due to it’s wonderful name, and easily interpreted range (85-110 is considered “non-suspicious”), it seems to be a pretty cut and dried matter for arm-chair doping analysts.

OFFs, ONs, and ESAs
At first glance, the name “OFF-score” could give the impression that it was a suspicion score, that is, a number that says “something is off here”, but it’s not. In fact, the OFF-score could better be described is a an indication that a persons red-blood generative process has been switched “OFF”, which is noted as an effect of blood-transfusion, or “coming OFF” a round of EPO or other “erythropoiesis-stimulating agent” (ESAs), or activity (like coming down from altitude). In contrast to the OFF-score, there is also an “ON-score”, which refers to the opposite case, that is a score that indicates the likelihood that a person’s RBC production has been switched “ON”, perhaps as a result of a round of EPO or some other stimulus for the generation of red blood cells. Below is a quote from an article entitled “Blood doping and its detection (Jelkman & Karsten 2011)“:

Some blood parameters, such as the concentration of Epo and reticulocytes (Ret), increase on administration of ESAs (ON-score), whereas they decrease after RBC transfusion or after the cessation of ESA administration (OFF-score)

A Jury of Your Peers
Now, the OFF-score is not a score of cheating, or even of suspicion – at it’s core, it is simply a number that is derived from the ratio of hemoglobin (oxygen carrying red blood cells – Hg) and reticulocytes (%R – baby red blood cells). In general, the expectation is that the more baby-RBC’s you have, the higher your Hb since baby-RBCs grow up to hold a lot of Hg. The formula for OFF-score is as follows;

Eq 1: ([Hb] (g/L) − 60 × √ (reticulocyte percentage)

There are several things to note when considering the meaning of this score:

  • Units Conversion – In the passport files that you will see, Hb is usually in the range of 13-16, whereas in the OFF-score calculation, that value is effectively multiplied by 10, having a range of 130-160.
  • This value is an expression of the underlying notion that in the average or median athletes body more reticulocytes generally means more hemoglobin.  In other words, this is a way of measuring an individuals ratio of Ret/Hg against that of their peers.  The fact that there is a range of “normal” values means that the actual Ret/Hg ratios in human beings is not fixed … some folks RBC’s may “live longer”, resulting in a lower level of Ret to produce a given Hg level, or vice-versa.
  • The most important thing to note, is that a value that is considered “of concern” or “suspicious” is one that lies outside of the 99.9th percentile (as prescribed by the WADA guidelines).

You’re 1 in 1,000 Baby: Cheaters & Outliers
I have often heard suspicious values in a passport as representing “a 1 in a million chance that this athlete is NOT doping”, or claiming that being outside of the prescribed OFF-score range indicates a 99.9% chance that the athlete IS doping – it should be stated unequivocally that this is not correct. An OFF-score that meets the 99.9% threshold (high or low) is literally a 1 in 1,000 score. That is, the statistics suggest that in the whole population of non-doped athletes that have been tested, 1 out of every 1,000 samples is outside of this prescribed range, in other words 0.1%.

Factors Influencing OFF-score
Plugging numbers into Eq1, it can be shown that if you have a high Hb coupled with a low-%R, that yields a high OFF. The idea being that if you have a high number of mature RBC’s without a correspondingly high %R, that you might have just transfused some RBCs, or recently came off of EPO and your body is now shutting down reticulocyte production to allow you to return to your natural equilibrium level. However, coming back from altitude (http://www.spectroscopynow.com/details/earlyview/10.1002/dta.1539/Altitude-exposure-in-sports-the-Athlete-Biological-Passport-standpoint.html?tzcheck=1) has been show to cause this effect, and the stress of stage racing has been shown to raise %R (see figure 1), which might manage to either raise OR lower OFF-score.

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