Thursday, July 27, 2006

Is there a definitive test?

Cycling's ruling body, Union Cycliste Internationale or UCI, will administer a second test to a different sample from Floyd Landis. This is what is commonly known as a copunter-analysis. In other words, they will use a different method than the previous screen to determine whether Flandis' elevated ratio is either a naturally occurring phenomenon or one caused by illicit actions of Landis'.

So, OK, these people aren't completely crazy.

But what constitutes a definitive test? And does the UCI use a definitive test method in their counter-analysis?

Let's go back to the experts.

According to a study performed by the Swiss Laboratory for Doping Analyses in Lausanne [C Saudan, N Baume, N Robinson, L Avois, P Mangin and M Saugy, "Testosterone and doping control", British Journal of Sports Medicine 2006;40(Supplement 1):i21-i24)] the ratio test used initially is what's known as an "indirect method." An indirect method by definition isn't definitive; it merely detects things that are frequently but not necessarily associated with illicit activity.

The study also indicates that the 4:1 ratio test (known as the T/E ratio) can be masked if the steroid is administered with ethanol.

It can be safely said that someone with half a brain administering to himself anabolic steroids and undergoing testing would administer the drug with a bit of ethanol and pass the test.

Clearly, at least to me, the T/E ratio test for competitive athletes is a load of junk. Ir produces high false positive and false negative rates, and the false negative rate can be easily jacked through simple methods, such as administering doasges with ethanol. That false negative rate can also be jacked by taking epitestosterone. This test is, simply put, easy to beat--if you have a reason to worry about it, that is.

OK, this indirect test, and perhaps any indirect test for that matter, relies only on half-baked science. What about a *definitive* test?

According to the aforementioned Swiss study, "(d)irect evidence may be obtained with a method based on the determination of the carbon isotope ratio of the urinary steroids" (i21). In fact it is mandatory for the International Olympic Committee to determine definitively through a secondary test whether the steroid is a natural steroid or an artificial one. Even if the ratio test method is tuned to the specific athlete over a long period of time to detect anomalous fluctuations in ratios, "there is a lack of definitive proof for the exogenous application of natural steroids," they write. Further, the authors of the study add,
One possible way of solving this problem is the ratio of the two stable carbon isotopes 13C/12C, which can allow the differentiation of natural and synthetic steroids. As exogenous testosterone or precursors contain less 13C than their endogenous homologues, it is expected that urinary steroids with a low 13C/12C ratio originate from pharmaceutical sources.

Does the UCI actually use such a method? Do they test for carbon isotope ratios? Or do they simply re-test Floyd with the same or another indirect method?

Even if such a definitive test is used by the UCI it remains to be seen whether cortisone would alter it.

Questions Linger. Can the administration of cortisone elevate naturally occurring testosterone levels or lower naturally occurring epitestosterone? Can extreme pain do it? What about extreme athletic performance? How about looking at the frequency of statistical outliers?

We'll take a look at the World Anti-Doping Administration's guidelines on elevated T/E ratios.

13 Comments:

Blogger DMC303 said...

I want to believe Floyd's innocent as much as anybody. I've been miserable all day since the news came out.

Two questions, though:

1) you state "It can be safely said that someone with half a brain administering to himself anabolic steroids and undergoing testing would administer the drug with a bit of ethanol and pass the test." Remember all the talk about Floyd having a beer after stage 16? Is that enough ethanol to mask results?

2) what I can't figure out is how someone who has presumably undergone a T/E test hundreds of times in his career, and probably 10 times in the month of July alone, failed by a not insignificant margin on one date alone.

I know nothing about the science and like I said, I'm desperately hoping he comes out of this innocent, but any light you could shed on these issues would be helpful.

3:01 PM  
Blogger Justin's Blog Site said...

The WADA guidelines on the T/E process seem reasonable and one would hope UCI would follow them to a T (pun intended). An IRMS test to determine if the T/E was exogeneous (of external origin) or of endogeneous (naturally occuring).

If endogeneous, they need to confirm using longitudinal studies such as "was his overall testosterone level abnormally high?" If endogeneous and he passes all endogeneous studies, he's off the hook.

Otherwise, they have to continue to study weather outside influences such as cortisone injections and alchohol consumptions can create elevated T/E.

4:01 PM  
Blogger Free Floyd said...

good questions dmc303. To (1), my informed guess is that no, a beer has an ethanol dose of about 20 grams. Street word is that ethanol can be used as a masking agent but how much is unknown. Peer reviewed literature shows that if he drank 6 beers or so (fewer if they are of the strong french country variety) he could actually elevate his T/E ratio. (see http://www.clinchem.org/cgi/content/full/43/7/1280). The plot thickens.

(2) is a more serious point. That might be the very point that the UCI makes in their final review, and that's enough to make his test a positive regardless of the science. The evaluative process gives primacy to the subjective evaluation.

Again, good points.

7:28 PM  
Blogger Free Floyd said...

Hi Justin -

What I described--the evaluation of the 13C/12C ratio--is the IRMS test (the IR is for isotope ratio). It appears that there's no requirement for either sample A or B to be tested using IRMS. I haven't heard whether IRMS was used for sample A or if it will for sample B. If it has already been used, things look very bleak for Landis. Further I can't find any pharmacodynamics documentation on any relationship between glucocorticosteroids and either E or T. If he's positive on the T/E ratio frankly it's bad science, but if they bother to do the IRMS and he comes out positive after that it looks pretty bad for floyd. Now the IRMS is also subject to false positives but those would be pretty extreme and related to diet. If they had a daily test record that would certainly help make a fair determination.

7:51 PM  
Blogger First_in_Floyd said...

Free Floyd armbands or bracelets are needed.

8:00 PM  
Blogger Jason A. Miller said...

Re: Carbon Isotope test

I'm in the middle of listening to Floyd's second journalist teleconference, done after the Madrid press conference, on Friday evening. Philip Hersh, of the Chicago Tribune, stated then, and has now written in an article, that L'Equipe is reporting that Sample A was in fact tested using carbon isotope analysis and did show the presence of external testosterone. I hope they're wrong. I don't read French, so I can't go to the source to verify Hersh's statement.

11:39 AM  
Blogger Free Floyd said...

If it's true that A was already tested using IRMS, then he's busted. i don't think he has a plausible excuse if an IRMS comes out positive for exogenous testosterone. maybe that six pack they gave him has testosterone in it. but it wouldn't matter how he got it in his system. if exogenous T is in his body, he's done. and I can go home and shut up!

6:14 PM  
Blogger Free Floyd said...

From the WADA release, which can be found at the bottom of the page here it appears that the IRMS is only applied to sample B if sample A comes postive through the T/E test. Thats what I've gathered before. The UCI and WADA documentation does not suggest that using IRMS for sample A is anything more than a recommendation, and that documentation does imply that there's a cost issue involved.

6:30 PM  
Blogger Jason A. Miller said...

During the aforementioned Friday evening teleconference, Floyd said he had never heard of IRMS until a journalist mentioned it. It seems that he knows very little about the process and is learning about as fast as the rest of us. He also said that he is pretty much on his own to arrange his defense. I hope he picked good lawyers and doctors.

9:39 PM  
Blogger MMB202 said...

More coverage on IRMS:

Amy Shipley of the Washington Post, 7/29/06:

Just one elevated testosterone-to-epitestosterone ratio test is not considered proof of a doping positive by WADA. To prove a doping violation, WADA demands that the charging agency examine other samples to ensure that the elevation is not the result of a naturally elevated T/E ratio.

Such follow-up analysis can be avoided if the sample is examined using what is known as the carbon isotope ratio test to distinguish natural from artificial testosterone.

Mario Zorzoli, chief medical officer for the International Cycling Union [UCI], said the French lab that analyzed Landis's sample was known to use the carbon isotope ratio test as part of its standard testing procedure, suggesting it was likely used in this case. The Paris lab director, however, could not be reached for comment.


Alan Abrahamson of the Los Angeles Times, 7/29/06:

Meanwhile, a French newspaper report, said lab results show the testosterone in Landis' Stage 17 sample was synthetically produced, not natural.

"I haven't heard anything about that," Landis' doctor, Brent Kay, said Friday.


Not sure what to make of any of this.

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