Thanks so much for this link:
The prosecution's theory is that Contador followed a course of injections of 200 micrograms of clenbuterol for three weeks and then his blood was extracted and through apheresis, the plasma was divided from the red blood cells. Several weeks later 200 milliliters of plasma was reinjected. If a person weighing 66 kilos urinates every three hours and a little over a liter a day, 12 to 24 hours after the reinfusion, around 50 picograms of clenbuterol would be present, the quantity found in Contador.
This does not say anything about separate red cell and plasma transfusions, though i guess it is implied.
The calculations IMO are fine, except more detailed than they need to be or in fact can be. There is a broad range of body weights, possible CB doses and plasma volumes that could account for the 50 pg/ml. I tend to agree with GJB that the prosecution is overdoing the detail (to the extent that reports like this accurately portray what the prosecution is saying). In the RFEC report, the prosecution worked with broad ranges, much more effective.
Contador's own pharmacokinetic study refutes the prosecution theory completely, pointing especially to the elevated level of toxicity that would be present in a person who had injected clenbuterol for three weeks. The cyclist's defense also emphasizes that for an athlete who undergoes as many tests as Contador - 32 in the seven months before the 2010 Tour - taking a banned substance for three consecutive weeks would be sheer folly. The study also questions WADA's calculation of the amount Contador urinates during competition, based on mid-Tour controls; WADA says 1.172 liters but Contador's team says he urinates as much as two liters. In the report, Contador himself states that if he only fills three-quarters of a sample container, it is for hygienic reasons. In 112 experiments using the WADA data, Tomás Martín Jiménez of the University of Tennessee found no scenario in which 50 picograms of clenbuterol could have been detected.
Point by point: There might be some adverse effects of CB at 200 ug per day for 3 weeks, but as I noted before, one does not need a dose nearly that high nor a regimen nearly that long to account for 50 pg/ml. 50-75 ug a day for a few days will do it. I don’t understand what WADA is up to here. I guess they want to use a dose that makes it impossible to refute the 50 pg/ml conclusion under any circumstances, but they should at least emphasize that 50 pg/ml is very reasonable with much lower doses (maybe they are, and this wasn't reported).
I agree that taking CB for three weeks would be very dangerous. I always thought if he took it, it was only for a few days. Of course, psychological factors like these don’t carry much weight in a tribunal like this. The assumption is the doper might do anything that worked. But personally, I've always doubted that Bert took large doses of CB for any extended period
Wrt volume passed, the presumption is that the more Bert passes, the lower the concentration in urine will be after a particular length of time. True enough, but with the broad ranges of estimates in play, increasing the urine volume will not be enough to make 50 pg/ml unlikely. Not even close, this seems to me grasping at straws.
Moreover, what increasing the urine volume estimate will do is increase the estimate of amount of CB he originally took. This doesn’t help the argument that it is contaminated meat, though I assume at this point Bert’s team has already accepted that you can’t get the 50 pg/ml from Euro-passed meat. IOW, their assumption is that if you are playing the outlaw meat card, it doesn’t matter how much CB was in your system. But this could backfire, because there might be estimates of how much meat contaminated at particular levels exist, based on the few positive tests of Spanish cattle, as well as on tests of imported meat. The higher the estimate of CB originally ingested, the lower the probability of contaminated meat at any level.
OTOH, the higher urine estimate also means a higher estimate of CB ingested intentionally, which helps support the arguments about side effects and dangers of taking a lot of CB. But overall, I don't think the higher estimate helps either side significantly.
I continue to think that the prosecution has a very strong case based the probability of contaminated meat. The case for transfusion I think is also fine, except for the DEHP test discrepancy, which is glaring. But setting that aside, the pharmacokinetics support transfusion far more than they do contamination.
The other main component of Contador's defense is Sheila Bird, a biostatistician and a world authority on mad cow disease who painted a bleak panorama of health controls in the European meat industry. According to Bird, and based on EU and Spanish regional data, only 900 of every one million cattle are tested before sale in Europe. Therefore, it can be affirmed that 99 percent of beef consumed in Spain has not been through any checks.
Discussed here before. In statistics, it doesn’t matter what the % of total is. All that matters is the absolute number of animals tested. If you test just 1000 cattle, the standard of error is, forgot now, but around 1-2%, I believe. Electoral polls work on the same principle. The key point is were the tests random. If they were, this argument holds no weight at all.
Pistolero: Yes, they must be representative or random, as I said. I'm still waiting to hear Bert's team claim they weren't.
Some more:
This is from an article that was previously linked here:
When [clenbuterol] was orally administered repeatedly to men twice a day, the plasma level reached the plateau within 4 d after the initial administration. At that time, the plasma levels of the unchanged form were 0.2 to 0.3 ng/ml and 0.5 to 0.6 ng/ml at doses of 20 and 40 μg/man, respectively.
Take the dose of 40 ug. A plasma level of 0.5-0.6 ng/ml. corresponds to 100-120 ng of CB in 200 ml of blood. Estimates of the amount Bert ingested are around 500 ng. (this was discussed on an earlier thread), that is, about 4-5 higher. If you multiply the 40 ug dose by 4-5 you get about 200 ug. This is reasonable, because the study cited showed a linear effect of dose vs. plasma concentration. I think this is how WADA came up with this figure.
But the 500 ng figure for what Bert ingested is an estimate only, it could easily be in a range of say 300-700 ng. This is quite reasonable, because there is considerable uncertainty in some of the very low CB values in Bert’s later samples, and because pharmacokinetics can vary somewhat from individual to individual (body weight differences as well as differences in physiology). If you take the lower 300 ng figure, you are down to 120 ug as an estimate of what he had to take per day. If you assume he infused 500 ml, not 200 ml., you can lower that all the way to about 50 ug. So rather than claiming Bert took 200 ug, it would seem much more sensible to argue he took a minimum daily dose of about 50 ug, which could have been more. Nobody can refute the possibility of 50 ug. It might not be correct, but it is far more likely than contaminated meat.
Also note from the above quote that the plateau value of CB in the blood was reached in four days. Three weeks are unnecessary, and I don’t understand why WADA is using that time frame.
The above study is quite old, and there may be newer data available, but I doubt they differ much.