Friday, September 28, 2012

Scientists Debate--Parisotto's Response to Ferrari

Point 1 
Michele Ferrari: The article "It is all about blood" of September 20, 2012 makes no reference to the Tour de France 2009: it proposes two graphs for Hemoglobin values 
​​and reticulocytes, without any historical (dates), logistical (altitude), and competitive context, comparing values ​​obtained in different situations, which interfere with the values ​​themselves. 

In particular, You cannot compare the results collected at the end of a three-week stage race with tests done out of competition, furthermore at altitude. Yet you decline to answer to such a serious FLAW. 
Robin Parisotto: The data which was initially reviewed (HERE) does not contain any reference to altitude exposure. Where or what evidence is there that these two samples were collected/tested at altitude? 
In a normal Biological Passport review such data is only made available when a full documentation package is requested to confirm/exclude any suspicions. The documentation package will include chain of custody details, time and place of collection, storage conditions,  time of transport, time of testing, testing laboratory, any relevant illnesses/injuries, exposure to altitude and any other relevant information such as blood donations.  
Until such time, a passport may be described (and communicated to an anti-doping authority) as being consistent with manipulation and deemed to be in breach of anti-doping rule violation (ADRV) until factors such as hemodilution, altitude exposure, illnesses or underlying medical conditions have been considered which suggest otherwise. As indicated previously, the analysis was posted in the context of an initial biological passport evaluation.
To address the "flaw, " the values in the graphs can be linked/viewed/confirmed by comparison with the results listed at the above website.  See the response to Point 3 and the chart for further clarification..

Point 2 
MF: Armstrong stayed at altitude (Aspen) from June 1, 2009 to June 26, 2009: therefore the tests on the 16th and 17th of June 2009 were taken at an altitude of 2400m a.s.l. 
So was the test dated August 12, 2009 (always Aspen, Armstrong raced in Leadville a few days later). 

RP: As this was data that was not evident in the website described above and also in the chart HERE:    which would ordinarily only become available to Passport members on request to the UCI through the Biological Passport process.   It is curious how a member of the public(As Armstrong has stated, Dr. Ferrari is merely a friend and their conversations have not been about matters of training or physiological analysis such as this) has such intimate knowledge of times, places, and conditions surrounding these blood tests.

Point 3 
MF: Since You are not informed enough about the discussed facts: the tests mentioned above are official values from USADA - UCI and each corresponds to a sample code. 

The correction factors are NOT applied in the COMMUNICATION of the result, but in any possible further EVALUATION: therefore Hemoglobin=16.0 is the measured value.

RP: The UCI is listed at the testing agency at this WEBSITE , so what is the point here? With regard to recorded vs corrected Hemoglobin values, to infer that a value of 16.0 equates to a value of 15.2 is making a simplistic interpretation of the biological passport evaluation process.

It is true that at altitude of between 2000 and 2500 metres a correction factor of eight is applied to the passport profile. However the correction factor is not automatically deducted from the recorded test value but rather applied to a predictive formula which adjusts the predictive distribution for low and high Hemoglobin values at that particular time of testing (see graphic below with upper and lower red lines indicating predictive values and blue line indicating the recorded values for each of the four passport parameters). 

In other words, if the predictive value was X but there was a confounding factor of altitude present, then this predictive value of X would rise to accommodate the influence of altitude (for those inclined, see WADA Athlete Biological Passport Guidelines for a full explanation HERE ) . The recorded value is not changed but the predictive value is, and if the recorded value is still increased above the adjusted high predictive value (or below the low predictive value) then this would be flagged as being an abnormal result. 

As previously posted though when evaluating a biological passport it is not about identifying or singling out any one abnormal result but rather about making a subjective assessment of the pattern of test results, magnitude of changes, and the times at which these changes may be occurring over a whole sequence of results (the profile). 

Point 4 
MF: Z-score is a number that expresses the probability that the test can not be the result of natural physiological changes (not necessarily doping, in any case). 
Z-score is used in the Biological Passport (Haematologica 2006,91:356-363 and UCI Technical Document 2.09), even though, as you say, often it takes a SUBJECTIVE assessment of a "picture of pattern, magnitude of changes and what time they are occurring", which sometimes lends itself to biased interpretations. 

RP: The four parameters used in the Biological Passport, as of today, are: Hemoglobin, %reticulocytes, OFF-score and ABPS-score. The passport is not a static tool or threshold based test but rather a continuous assessment of blood parameters that when assessed as a 'whole' can give very clear and objective patterns which may be reflective of blood manipulation. Factors such as competition, altitude, illness/injury, and pathology are always considered, however, before making final recommendations or conclusions about any suspicious profile.

Point 5 

MF: See comment to Point 3. 
I find it very surprising that such an Expert Scientist as Yourself has expressed an "absolute certainty of blood manipulation" in the evaluation of data of which You had only partial knowledge. 

RP: Two points that have not been explained by Ferrari and which would be pivotal in an evaluation of such a profile are:

1.      1) Why had the Hemoglobin and Hematocrit increased during the 2009 Tour race when in just the previous race they had dramatically decreased (by almost 15%). The point here is not the decrease in Hemoglobin during the Giro as this probably reflects  hemodilution as pointed out by Ferrari (and was not suggested by me that this was due to blood withdrawal) but rather why the same phenomenom did not occur during the Tour de France.
         2)Why were reticulocyte levels decreased when Hemoglobin was increased in the two tests allegedly collected/performed at altitude prior to the 2009 tour. This scenario is consistent with previous administration of stimulating agents such as EPO and or previous blood re-infusion. In the original post …. from October 16, 2008 the average reticulocyte levels are 1.1 but from May 18, 2009 the average reticulocyte levels are 0.6.’ This change/reduction in reticulocyte production during competition is not due to hemodilution however as percentage values for reticulocytes are not affected by this physiological response. This reduction reflects a blunted response to normal red blood cell production and can be achieved by micro-doping over an extended period of time or blood doping over shorter periods.

Without a satisfactory explanation of these two key points, my suspicion of blood manipulation would remain as my conclusion in the initial biological passport evaluation.


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