Ever since the Floyd Landis scandal broke in July 2006, I’ve been puzzled and bothered by what seems to be an odd inconsistency in the story. As followers of the Landis saga know, France’s anti-doping lab reported that Landis tested positive for the use of synthetic testosterone on Stage 17 of the Tour de France that year. Just over a month ago, the arbitration panel that heard Landis’ case ruled against him in a 2-1 decision which has been controversial (among dedicated followers of this story, anyway), to say the least.
The thing that’s bothered me is this: It was well-known before the alleged positive result that Landis had a therapeutic use exemption (TUE) for cortisone, in order to treat a hip problem. Mid-way through the Tour, a New York Times Magazine article told the story of how Landis had injured his hip several years before, and how he’d managed to continue to compete despite the discomfort. After the Tour, the story announced, Landis would be getting a hip replacement using the new (to this country) Birmingham Hip Resurfacing technique.
The basis of the case against Landis is the alleged finding of synthetic testosterone in his system. Testing of other B samples from the Tour yielded similar results to the Stage 17 sample in several instances. Whether or not the test results indicate the use of testosterone is still a matter of debate — except for the two arbitrators who ruled against Landis.
What’s interesting to note is that during all of this testing, the one thing that should have been found — an otherwise banned substance without a proper medical exemption — was cortisone. And yet, there’s no solid evidence that LNDD found, much less reported, that Landis had any synthetic cortisone in his system. The question of why this was never found or reported (and if reported, then determined to be covered by a TUE) has lurked in the back of my mind ever since Landis released the lab documentation package (LDP) a year ago.
Tonight, I decided to do a little investigating, focusing on two areas. First, what kind of tests are used to determine a that an athlete has used cortisone, and can it detect cortisone taken orally or intramuscularly (which is how I presume Landis received the medication). Second, what are the technical requirements for reporting a positive result for the use of synthetic cortisone. Figuring the best place to go would be the World Anti-Doping Agency’s web site, I searched high and low for a technical document regarding cortisone tests.
What I found may partly explain why LNDD didn’t report a positive result for cortisone. First off, is a document that WADA publishes that sets forth basic requirements for the detection of various compounds, like cortisone (referred to as glucocorticosteroids in WADA’s various documentation). In WADA Technical Document TD2004MRPL, the agency requires that all doping labs should be able to detect a minimum concentration of glucocorticosteroids of 30 ng/ml.
So, the next question is: a concentration in what — blood or urine? And to answer that question, one might look for a technical document referring to the methods of detection and requirements for reporting an adverse finding. As the document above notes:
The MRPL is not a threshold, nor is it a limit of detection or a limit of quantification. Adverse Analytical Findings may result from concentrations below thos listed in the table.
So we still don’t have any indication of what constitutes an adverse finding for cortisone, at least not in the MRPL. What of a technical document listing the criteria for a positive (non-negative in ADA-speak) result? There isn’t one. Nada. Zip. Zilch. Zero.
Whether or not LNDD or any other lab tests for cortisone, there is no standard set forth that specifies what would constitute a positive test — at least none available on WADA’s site. Search for similar technical documents on EPO and testosterone and you will find information about the testing procedures to be used and what constitutes a positive test result.
For cortisone, there does appear to be some research into developing testing standards, and that research appears to focus on detecting cortisone metabolites in urine using various techniques. Drs. de Ceaurriz (Criteria setting for the misuse of glucocorticosteroids.), and Leinonen (Development of a universal screening procedure for acidic, neutral and basic doping agents in urine.) in February 2005 and Dr. Kazlauskas (Improved methodology for detecting and confirming the abuse of glucocorticosteroids.) in March 2005 wrote project reviews for research related to glucocorticosteroid detection.
The reviews by Dr. de Ceaurriz and Dr. Kazlauskas seem to be most applicable. Still, no one addresses the issue of what currently constitutes a positive test. Looking at the banned substance list for 2005, it appears that various patches that contain such medications no longer require a TUE. So whatever amount would show up by using such patches clearly wouldn’t be a violation. But what would be?
That’s the open question. Just as one open question from the Landis case is, if cortisone is a banned substance and Floyd was known to be using it, how come LNDD didn’t find it? Or perhaps they did, but mis-identified it as something else.
In the article A Dangling Issue at Trust But Verify, TBV notes:
As historical note, Duckstrap looked at this in March:
At DPF, Duckstrap sees two dots that might connect — cortisol metabolites and unidentified peaks that may have skewed the carbon isotope ratio.
A different discussion is looping around the issue of whether Landis’ cortisone was detected, or not detected, reported or not reported or what. What seems agreed is that the data shows it was detected in at least some tests, but it seems not to have been explicitly noted for reasons unclear — perhaps there was an undocumented discretionary choice not to follow up, or there was an undocumented TUE evaluation. Rare participant Dumas is asking some interesting questions and bringing in good new information.
And slightly later [Duckstrap] thought the numbers were suspiciously similar:
Just to add further fuel to the speculative fire, I will point out that metabolites of cortisol have four acetylation sites, instead of the two found on metabolites of T. The number of carbons in cortisol metabolites is 21 vs. the 19 in T metabolites. If a peak containing primarily cortisol metabolites were a significant contaminant or were misidentified, then because of the highly negative CIR of the acetic anhydride used for derivitization (-53 per p. 351), a cortisol metabolite with a corrected CIR of -24 would have an uncorrected value of -32 in the IRMS, exactly in line with the observed CIR of the mystery “5bA” in the Landis F2 sample, and with the putative “5aA” sample in his F3 sample.
Duckstrap’s observations are very interesting. Perhaps what LNDD found wasn’t a positive result for testosterone. Perhaps it was cortisone, instead.
It would help, of course, to have a technical document that lays out the standards for a positive cortisone test. It could even shed an interesting light on Landis’ results. Especially given what Duckstrap notes about the CIR data, above.
In the back of my mind, I keep wondering: Did LNDD really find synthetic testosterone, or did they find cortisone, instead?
I wonder if we’ll ever know.
In the back of my mind, I keep wondering: Did LNDD really find synthetic testosterone, or did they find cortisone, instead? I wonder if we’ll ever know. Rant I don’t see how that such questions be addressed?
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If data was distroyed, wiped or rewritten – how on earth could we? And it seems that theb powers that bee seem not to “worry” about such small details. Of course if they were to pay attention and actually act on the in´formation that is now avaiable – it would mean they would have to admit that this whole Landis Case was nothing but a badly organised peice of power-playing amongst them.
To my mind, related issues here are the over-written data files and the wiped hard drive from LNDD. These are rather suggestive that LNDD had something to hide.
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Regarding the over-written data files: the LNDD tech testified that when they ran tests they didn’t like the results and so they did them over, and saved the resulting files using the same name as the original data file name. OK, it is possible that somewhere there is something which says that is the data looks a certain way, it indicates there is a problem and you need to correct the problem (equipment set up? sample processing?) and re-do the test. If that was the case, the techs should have been more specific in their testimony, and there should be supporting documentation in equipment manuals (which they didn’t have in the first place) or lab SOP or WADA regs or whatever. Otherwise these do-overs can be interpreted as running the tests over until you get the results you want. In any case, the original data should have been retained so that it could be used to back up whatever reason they had for re-doing the tests. I suppose just about anybody who uses a computer at some time has mistakenly overwritten some file, but my impression from the testimony was that this was done several times and deliberately.
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The wiped hard drive is even more troubling. One has to deliberately take action to wipe a hard drive, so there is no other conclusion that could be drawn here other than there was something on that drive that LNDD didn’t want to become public. Whether is was something that would have damaged their case against Landis or just something else that would have been embarrassing to LNDD, who knows. Maybe someone was downloading porn on the lab computer in their spare time.
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If we had all this missing data, it is possible that it might clear up some on the questions that have been raised about the tests. Maybe that would make a clear cut case against Landis, but if that was the case, I think LNDD would have produced the data. So maybe what was destroyed would have helped Landis. But we’ll never know.
http://www.bloomberg.com/apps/news?pid=20601109&sid=aDe3l5g45w6E&refer=home
ORG,
Very interesting article. I’d heard some rumblings about a way to sabotage the EPO test, but my source wouldn’t provide more than that. Apparently, someone at Bloomberg put the whole story together. Thanks for the link.
ORG, OMG! So an athlete can avoid EPO detection by flicking a few flakes of LAUNDRY SOAP into his urine? LOL! No WONDER Dick Pound is paranoid. You have to wonder if Mayo was aware of this trick.
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Rant, you raise good questions. Can the labs actually detect cortisone in an athlete’s sample? If not, why not? When the labs prepare an athlete’s urine sample, can they filter out the cortisone, so that it could not interfere with whatever else they might be trying to detect (such as testosterone)?
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I’m posting actively on the TBV discussion of this issue, so I won’t repeat myself here … except to say that FL never raised the issue of possible cortisone contamination of LNDD’s adverse finding, and for this reason I don’t think USADA needed to address the issue.
Larry,
I’ve seen your post and comments at TBV. I believe that you’re correct in saying that since Team Landis didn’t raise the possibility of contamination by cortisone that USADA wasn’t required to refute that possibility. I suspect that the Landis side felt that showing ISL violations was enough. Perhaps, however, at the CAS level, the issue of contamination will take on some life.
What is even more frightening is that they do not seem to know the difference, whether on purpose to cover up – or unknowingly. Either case – this lab should be sanctioned from testing. WADA must be made to uphold its own certification rules and not allowed to change said rules in mid crissis.
From a legal stand point, the possibility of cortisone contamination was irrelevant. It’s not something that could be proven from the Landis side, with the information provided form LNDD (heck, the lab pack couldn’t even prove doping). Therefore, the possibility that the urine was contaminated is purely hypothetical and not relevant to the case. WADA rules do not address this. It is a little shocking to find that WADA/UCI doesn’t test for cortisone. However, I can’t say it upsets me (too much). I have never accepted that doping includes therapeutic drugs like cortisone, cold medicine, or pain killers. Everyone is all in huff about ventolin and asthma in cyclists (forget about that hacking cough I always get after a hard ride). Does anyone really believe that Patacchi wins races because he has an inhaler?
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Moving along (sorry about the side rant), I think that it is very likely that some of the C13 is from Floyd’s cortisone injection. From the testing “methodology” utilized by LNDD there is no way to prove or disprove this theory. Once Floyd established the ISL violation he could have inserted this theory (but at what price? could the cortisone theory have opened another can of worms?), but his theory would serve no purpose except to provide a distraction. Once the ISL was established, it was up to the ADA to prove that the test was valid – not Floyd’s responsibility to show theories. Why would he help them by providing a plausible explanation that they could focus on disproving?
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What I would like to see, is someone refute Larry’s post over at TBV. His explanation regarding the ISL violation seems rock-solid. If he is correct, then the injustice perpetrated by the arbiters (all three of them) is truly sad.
If I was a scientist interested in the issue of whether or not cortisone contamination could produce the results seen in the Landis case, I probably would test a number of people. I’d have some take T, some take C, some both and some neither, double blind of course, and see whether or not the 2 substances could be clearly distinguished or not. But if trying to refute the LNDD results, there’s always the problem that we don’t know exactly how they conducted all steps in their work, and maybe they did something that would change the results in the hypothetical experiment described above.
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If cortisone contamination were a known issue in testing, and there was some standard method of dealing with the problem, USADA could show that a lab dealt with the issue, IF THE LAB HAD GOOD DOCUMENTATION of its procedures. “We knew FL was using C per his TUE, so we did such and such to sort it out.” But LNDD’s documentation is faulty, and their testimony at the hearing seems to me to be a lot of trying to spin things after the fact to explain away issues the Landis camp raised. We don’t really know how they IDed things, because they started out saying they use RRT, but when M-A threw a spanner in those works, Brenna backed up and introduced the visual inspection idea (which to my mind is just a fuzzy version of RRT).
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So we have a lab that did not have a manual for the equipment they used, did not know how to properly set it up (the MM ears, running test over pressure), failed to adequately document what they did, destroyed electronic documentation, produced 2 different versions of the “original” documentation, has unexplained discrepancies with the rider ID numbers, used white-out to “correct” alleged errors, rendering it impossible to see what was “corrected”, apparently has no written SOP, and we are supposed to believe their results?
1999 Tour per
http://www.britannica.com/eb/article-9343162/Lance-Armstrong:
During the Tour he fought allegations of doping because traces of a banned substance, corticosteroid, from a prescription skin cream he used for saddle sores, were found in his urine.
per VeloNews, via
http://www.tdfblog.com/lance_armstrong_2004/index.html:
The UCI and the Tour de France instituted a new test for Corticosteroids. On July 19, 1999 – in the middle of Armstrong’s first successful assault on the Tour – the French newspaper Le Monde ran an article citing laboratory sources as saying that samples from several riders – including Armstrong -had shown traces of the banned drug. The levels were below those required to show a positive on the new test, but the results raised suspicions. The UCI later confirmed the result, but noted that the traces were from Armstrong’s use of the topical ointment Cemalyt. The governing body also later announced that it had a prescription on record. As a result of both the low levels and the prescription, the test result is not officially considered to be a “positive.” – Editor
Art,
Right you are about the UCI and corticosteroid testing. What’s puzzling to me is WADA’s lack of clear-cut standards and procedures. For an organization whose mission is to “harmonise” anti-doping practices at the various labs around the world, this seems odd, to say the least. WADA doesn’t publish any technical document or standard for positive tests, at least none that can be found on their site. One can easily find information for testosterone, anabolic steroids, EPO and other drugs. Given how long corticosteroids have been around, it seems like a pretty glaring omission. And it seems to leave the testing and determination of what a positive result is up to each lab.
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That said, an emailer sent me links to the proceedings of the 2005 Cologne conference where several articles were presented about new techniques for testing for glucocorticosteroids. According to the articles, WADA added them to their banned list starting in 2004. In 2005 they took off the requirement that use of a patch would need a TUE, which appears to mean a situation like Armstrong’s in 1999 would have been a positive test from 2000 – 2004, but in his last year on the Tour it again would have been a negative test. Confusing, no?
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I’ll be writing more about those articles later today or tomorrow.
Rant –
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Your post here is terrific, and deserves a better response from me than I’ve had time to give you.
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You’ve done great research on how cortisone is detected, and on the guidance (or lack of guidance) from WADA on how a lab should detect cortisone. I’m coming to realize that WADA gives a great deal of flexibility to its labs. The International Standard for laboratories (ISL) promulgated by WADA governs what the WADA labs are supposed to do, but the ISL leaves a lot of territory uncovered. And in those areas where the ISL provides guidance, in many cases the ISL requires the labs to develop standards or criteria satisfying minimum requirements set forth in the ISL. So on an operational level, the rules that the labs are supposed to follow are their OWN rules. The ISL places some limits on what these rules might be, but does not require the rules to be the same from lab to lab.
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We’ve seen this play out in practical terms in the Mayo case, where the EPO testing performed by Ghent is not the same as the EPO testing performed at the LNDD. WADA has standards for EPO testing, but apparently these standards still allow the labs some leeway to develop different procedures to test for the same drug.
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Now, maybe this is as it should be. Maybe it’s not possible to impose uniform procedures on different labs, in different places, using different languages, with different budgets and different access to equipment, operating in different environments. Also, you don’t want to impose procedural requirements on labs that are so rigid that they cannot keep up with advances in the science and make improvements.
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I think this is what you’ve encountered with cortisone, where the ISL requires the labs to be able to detect cortisone within certain limits, but is silent about the relevant details (like, do the labs detect cortisone in urine or in blood?). WADA leaves it up to each lab to develop rules to deal with cortisone, with the requirement that the rules meet minimum standards (such as the ability to detect cortisone within the prescribed limits).
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The problem I’m seeing is not with the ISL itself, but with the system WADA uses to prosecute doping cases. If the ISL is written so that most of the applicable standards are written by the labs into their standard operating procedure (SOP), then we need to see the SOP to figure out what the hell is going on. But we don’t have access to the lab SOP. In fact, from my discussions over at TBV, I’m not even sure that the FL team had access to the LNDD’s SOP.
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Do you want to know if LNDD tested for cortisone? It should be in their SOP. Want to know if the “chemistry” performed by the LNDD on FL’s S17 sample included a procedure to remove cortisone from the sample, so that the cortisone could not interfere with the testosterone? The answer is in the LNDD’s SOP.
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But we don’t have the SOP. We have the ISL that was used to guide LNDD in its preparation of its SOP … so we know that where the ISL mandates a particular procedure (like 3 ions for T/E testing), that procedure is required to be in the LNDD SOP. The mandated procedure may or may not actually be set forth in the LNDD SOP, but we know it’s supposed to be there, and if the LNDD fails to follow the mandated procedure, we can prove an ISL departure.
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The problem we run into is with all of the cases where the ISL does not clearly mandate a given procedure, but instead gives the labs the leeway to adopt its own procedure. If the ADAs are not required to disclose the SOP, then you’re pretty much proceeding in the dark when you ask the kinds of questions we want to ask … such as, “was it something else”?
Larry:
Do I have this straight: the ISL says the labs are supposed to be able to detect cortisone, but leaves the how up to each lab. The labs in turn are supposed to develop an SOP, but at least for LNDD, if such exists it is TOP SECRET. For all we know, there SOP could be sacrifice a chicken and read the entrails. Now given, that probably is an exaggeration, but unless we have an actual SOP, we have no way of knowing if they actually do anything, and if they do, is it legitimate. Given the problems they had that we do know about, it is quite possible that they either failed to do anything to either detect or eliminate cortisone, or indeed any other possible contaminant. Or it may be that they did indeed do something, but didn’t document it and so we are supposed to just take their word for it. Personally, I would place more reliance on a document produced before there were any questions raised than after the fact spin.
William, I am painfully trying to figure this out. But I think you have it in a nutshell. To win, the athlete has to prove a departure from the ISL. The ISL in many cases requires the lab to develop the applicable standard and include it in the lab’s SOP. The lab does not appear to be required to disclose the SOP. So how is the athlete supposed to prove the ISL departure?
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Well, you can run up against a portion of the ISL that requires something specific, like the 3 ions required to compute the T/E ratio, or the rule that says you have to have different analysts doing the A test and the B test.
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Or, you can try to infer what’s in the lab’s SOP by looking at what the lab actually did.
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Otherwise, you’re screwed. The lab’s presumed to have acted in accordance with the ISL, the athlete has the burden of proving a departure from an ISL standard, and the lab’s not telling the athlete what the standards are.
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Man. I hope there’s something wrong with how I have this figured out.
To all –
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Yours truly is an IDIOT. Until today I completely failed to grasp exactly how badly the ADA system is screwed up. I hope you all know me to be a reasonable man, someone always willing to consider that there’s another side to every story, and that there’s probably a way to make any system work if you try hard enough and give it enough effort.
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Then I read Procedural Ruling No. 2 in the FL case. And I could feel my blood boiling. It’s Catch-22, in all of its perverse glory.
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Here’s the catch:
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1. To win, the athlete has to prove a departure from the ISL.
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2. In most cases, the ISL requires the lab to adopt standards or criteria, meaning that to win, the athlete will have to show a departure from the lab’s standards or criteria.
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3. The labs are not required to disclose the standards or criteria.
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AND, I’VE SAVED THE BEST FOR LAST:
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4. The athlete’s legal team is not permitted to ask questions about the contents of the standards or criteria.
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You could throw in a #5 if you wanted, which is that the standards and criteria are presumed to be valid, in the absence of evidence produced by the athlete to the contrary. What evidence could the athlete produce? AHA! Please see points 1-4 above.
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I think I’ve had it with this whole business. Hell. I don’t even RIDE a bike. I WALK places. Hell, maybe that’s my problem. Maybe if I rode hours every day in traffic, surrounded by steel-clad two-ton 4-wheel things while I (clad in lycra) was perched on a two-wheel 20 pound thing, I could cope with smaller matters such as the cynical denial of due process.
The irony: the ADA beats Floyd on a technicality.
Larry,
I think you’ve hit the nail on the head. No matter how an athlete like Floyd might wish to argue ISL violations, it’s Catch-22. Landaluze was one of very few exceptions, because the violation was so glaring that it couldn’t be rebutted (and the UCI didn’t even try, for that matter).
Michael,
The irony, indeed.