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The drugs (tests) don't work...

LangerDanLangerDan Posts: 6,132
edited July 2008 in Pro race
According to todays IHT

OLYMPICS
Study shows problems with Olympic-style tests
By Gina Kolata Published: June 26, 2008

Athletes who want to cheat by injecting themselves with a performance-enhancing drug that boosts their blood cell count can do so with little risk of getting caught, a new study indicates, possibly exposing another flaw in what is regarded as the world's toughest anti-doping program.

A urine test that is supposed to detect the drug, and that will be used in the Tour de France next month and in the Olympics in August, is likely to miss it, the study says. The substance, recombinant human erythropoietin, known as EPO, stimulates bone marrow to speed up production of oxygen-carrying red blood cells. And with more blood cells, endurance athletes like cyclists and distance runners can perform better.

EPO is banned by the World Anti-Doping Agency, an international group that promotes and coordinates efforts to stop doping in sports and whose program is followed by the International Olympic Committee. The agency defends its EPO test and questioned the latest study.

Although athletes have said EPO is in widespread use, few have tested positive. Most of the athletes who have been linked to doping in recent years have been caught not through drug testing, but rather through criminal investigations. In the August 2006 issue of the journal Blood, the American lab accredited to conduct EPO testing reported only 9 positive tests out of 2,600 urine samples.

The new study may help explain why: the test simply failed.


The study, to be published Thursday in the online edition of the Journal of Applied Physiology, was conducted last summer and fall by a renowned lab in Denmark, the Copenhagen Muscle Research Center. The investigators gave eight young men EPO and collected urine samples on multiple occasions before, during and after the men were doping. The men's urine samples were then sent to two labs accredited by the World Anti-Doping Agency, and EPO tests were requested.

The first lab found some samples positive and a few others suspicious. (A suspicious result does not bring sanctions for doping.) The lab also declared a sample positive, although the man had stopped taking the drug and it should have been gone from his urine. His previous urine sample, obtained when he was taking EPO, was negative in this lab's test.

The second lab never deemed any urine sample positive for EPO and found only a few to be suspicious. The two labs did not agree on which samples were suspicious.

The anti-doping agency's rules say that if an athlete's urine shows traces of EPO, it must be tested again by a different accredited lab. The athlete is declared guilty of doping only if the second lab also detects EPO. By that rule, none of the subjects would have been charged with using EPO, even though their red blood cell counts rose and their performance on an endurance test improved.

"The paper certainly is an eye-opener," said Don Catlin, the chief executive of Anti-Doping Research, a nonprofit group in Los Angeles. "It's quite remarkable."

But Olivier Rabin, scientific director of the World Anti-Doping Agency, said his group had tested its labs, sending samples of urine from people who were taking EPO and from people who were not. In general, he said, the labs agreed. But Rabin added that when the agency sends samples to its labs, they are not sent anonymously — the lab knows the samples are from WADA.

The agency does not share data from the tests on its labs, so it was not possible to determine how the organization's research compared with the latest study.

"I have never seen such a drastic situation as the one reported in this article," said Rabin, who questioned whether it reflected the true state of EPO testing.

The findings in the latest study should be no surprise, said Charles Yesalis, a professor of sports science at Pennsylvania State University. For decades, he said, anti-doping authorities have claimed they have tests that work and for decades athletes have been taking drugs without getting caught.

The anti-doping authorities, he said, "remind me of little boys whistling in the graveyard."

Still, the study's lead author, Carsten Lundby, a physiologist at the Copenhagen Muscle Research Center, said he had mixed feelings about publishing the paper. His concern was that if he laid out the test's weakness, he was telling athletes that they can probably take EPO without getting caught.

"It's a nasty problem," said Dr. Joris Delanghe, a professor of clinical chemistry at the University of Ghent in Belgium. He and Dr. Michael Joyner of the Mayo Clinic wrote an editorial accompanying the paper.

The finding is especially provocative, Joyner noted, because only last month, another study, by researchers in Sweden, called into question another urine test for a performance-enhancing substance, testosterone. The investigators showed that a substantial number of men and, in particular, Asian men, have a gene deletion that allows them to take testosterone and reap all the drug's benefits but escape detection. The testosterone test, too, will be used at the Olympics and the Tour de France.

The EPO study involved eight young men, university students in Copenhagen, who agreed to be injected with EPO over a four-week period and have their blood cell counts and athletic performance monitored before, during and after they took the drug. The EPO regimen was similar to those used by athletes who were trying to cheat. The men had EPO injections every other day for two weeks to get the process going and then had one injection per week to maintain their increased blood cell production.

The researchers were primarily interested in learning whether the young men's athletic performance improved — it did, and markedly so. At maximum effort, the men's performances improved by 9 to 16 percent. But at a slightly lower level of exertion, performance improved by 50 percent, Lundby said. Athletes taking EPO can go 50 percent longer at that somewhat lower level of effort, which can make a major difference in an endurance event like the Tour de France or a marathon, Lundby said.

The investigators asked whether the sole reason for the improvement was increased numbers of red blood cells, and it was. But they also realized they had an opportunity to investigate the validity of the EPO test. So, without telling the anti-doping labs what they were doing, the investigators sent the men's urine samples for EPO testing.

One of the two labs, which the researchers refer to as Lab B in their paper, never declared any sample positive, even when the men were taking high doses of EPO every other day. Lab A was inconsistent. It found EPO during the high dose phase. But in the maintenance phase, it found EPO in only 6 of the 16 samples.

It is not terribly surprising that the labs disagreed, researchers said. The EPO test, like urine tests for other hormones, including growth hormone, is extremely difficult. The lab must look for tiny chemical differences between the EPO a person makes naturally and EPO that is injected as a drug.

"It's super-difficult," Lundby said. "The difference between the EPO you have in your body and the recombinant EPO is not very great."

The drug, which is used to treat patients with kidney disease, cancer and other illnesses, is made by animal cells, typically Chinese hamster ovary cells. Researchers said there were new forms of EPO and new ways of getting its effects without injecting recombinant EPO, making it even harder to detect doping.

"The list of these substances is growing," Lundby said. "From a patient's point of view, it's great, but from an anti-doping view, it's bad. The list of substances you must test for will grow and grow."

And the possibility of a 50 percent improvement in performance has to be tempting, Lundby said. "So what do you do? You take it."

"It doesn't sound good for anyone who wants a drug-free sport," he added


(Sorry about the long post!)
'This week I 'ave been mostly been climbing like Basso - Shirley Basso.'

Posts

  • iainf72iainf72 Posts: 15,784
    Amazed at the lack fo comments on this.

    Mind you, I'm hardly surprised. It's like the biological passport scheme - Sounds good in theory but they'd never tested it to see if they could spot wierdness.
    Fckin' Quintana … that creep can roll, man.
  • iainf72iainf72 Posts: 15,784
    Another summary. DaveyL, what's your science-guy take?


    To prevent a possible misuse of rHuEpo, this is tested in urine samples collected from athletes by World Anti Doping Agency (WADA) accredited laboratories. Recently the test has met serious critiques, and the aims of the present study were to investigate the detection power of the test as well as the variability in the test power comparing the results of two WADA accredited laboratories. Methods: Eight human subjects were studied for seven weeks and treated with rHuEpo for four weeks with two weeks of "boosting" followed by two weeks of "maintenance" and a post period of three weeks. Urine samples were obtained during all periods.


    Results: Laboratory A determined rHuEpo misuse in all subjects during the "boosting" period, whereas Laboratory B found no misuse, with one sample to be negative, and the remaining seven to be suspicious. The detection rates decreased throughout the maintenance and post period when total hemoglobin mass and exercise performance were elevated. During this period, laboratory A found only two out of 24 samples to be positive, and three to be suspicious, and laboratory B found no positive or suspicious samples. Conclusion: This study demonstrates a poor agreement in test results comparing two WADA accredited laboratories. Moreover, after the initial rHuEpo "boosting" period the power to detect rHuEpo misuse during the maintenance and post periods appears minimal.
    Fckin' Quintana … that creep can roll, man.
  • DaveyLDaveyL Posts: 5,167
    My head hurts
    Le Blaireau (1)
  • iainf72iainf72 Posts: 15,784
    DaveyL wrote:
    My head hurts

    Ha.

    The differences between the labs is a shocker though - They're both WADA accredited apparantly.
    Fckin' Quintana … that creep can roll, man.
  • Robmanic1Robmanic1 Posts: 2,150
    Wasn't this the whole basis of Landis' argument, the fact that the he was tested positive at the French testing lab and negative at others?

    Seems we're still a million miles away from drug-free sport, fill yer boots boys (and girls)!
    Pictures are better than words because some words are big and hard to understand.

    http://www.flickr.com/photos/[email protected]/3336802663/
  • KléberKléber Posts: 6,842
    It's one paper which tested a very small sample saying people might be able to get away with it: do you feel lucky, punk? If you're a pro rider, do put your reputation on the line and just hope you're ok?

    But clearly with microdosing, out of competition use and more, it's clear that riders are still using old methods.
  • blazing_saddlesblazing_saddles Posts: 19,227
    This story, (from the NY Times?) is doing the forum rounds.

    What can you say?
    I expect the testing bodies to ignore it's findings for as long as possible.

    Landis fans will cry "foul", once again. Completely ignoring the fact that this is
    in regard of r EPO, not synthetic testosterone.

    However, CAS might feel this sufficient grounds to uphold his appeal. Where Landis goes, Kessler et al can follow.

    That will mean we once again return to the uber-fueled golden era of EPO and our cleaner, new world goes out of the window.

    In the meantime, Mayo will still be p**sed about.
    Heras????

    Oh, and Prudhomme will apologize to Floyd and re-instate him as Maillot Jeune, 2006. :roll:
    "Science is a tool for cheaters". An anonymous French PE teacher.
  • DaveyLDaveyL Posts: 5,167
    Eh? On the basis of doubt over the EPO test, Landis, who tested positive for synthetic testosterone, gets acquitted, but Mayo, who has been done for EPO, doesn't? I assume this post is ironic.

    There is no way CAS are throwing out the case on Landis due to these findings. We are talking a totally different test here.

    I'm off to try and find the original article and have a read.
    Le Blaireau (1)
  • Garry HGarry H Posts: 6,639
    This story, (from the NY Times?) is doing the forum rounds.

    What can you say?
    I expect the testing bodies to ignore it's findings for as long as possible.

    Landis fans will cry "foul", once again. Completely ignoring the fact that this is
    in regard of r EPO, not synthetic testosterone.

    Agreed, Floyd was caught with synthetic testosterone. When's the judgement out on him? Thought it was June
  • LangerDanLangerDan Posts: 6,132
    It's not a newspaper investigation, per se. The American Physiological Society which publishes the Journal of Applied Physiology issued a press release yesterday to announce the findings.

    http://www.eurekalert.org/pub_releases/ ... 062608.php

    What is quite interesting but will get lost in the "tests don't work" headlines is how the EPO dramatically improved performance (endurance, I'm assuming) at sub-maximal effort.
    'This week I 'ave been mostly been climbing like Basso - Shirley Basso.'
  • blazing_saddlesblazing_saddles Posts: 19,227
    DaveyL wrote:
    Eh? On the basis of doubt over the EPO test, Landis, who tested positive for synthetic testosterone, gets acquitted, but Mayo, who has been done for EPO, doesn't? I assume this post is ironic.

    I'm off to try and find the original article and have a read.

    Yes. Just a snide comment upon the UCI's selectivity. Although, they are pretty consistent on their treatment of these two riders.

    Article link. (you have to wait for the nice Ralph Lauren/Wimbledon advert to play. :wink): :-
    http://www.nytimes.com/2008/06/26/sport ... 12wq//b7LA)
    "Science is a tool for cheaters". An anonymous French PE teacher.
  • On the basis of this, which appears a sound paper, can one conclude that a/ Anyone who says that a cyclist can win a grand tour or mountain stage clean is lying, and/or b/ Anyone not on epo is cheating both their teammates and sponsors?
    That is the most interesting post I have ever seen on a bike forum.
    50% :shock: :shock: :shock:
    Dan
  • iainf72iainf72 Posts: 15,784
    Garry H wrote:

    Agreed, Floyd was caught with synthetic testosterone. When's the judgement out on him? Thought it was June

    It's supposed to be June but it's looking unlikely.

    I know everyone says it's different but Landis' argument is that what has been called a positive for synthetic testosterone is not positive. And what this EPO study is showing is the vast differences which can occur in lab-land. So if one lab calls it positive and another doesn't, which is right? And he's been given even more of a fighting chance because his initial test performed poorly.

    Do we need a 3rd party to monitor WADA?
    Fckin' Quintana … that creep can roll, man.
  • DaveyLDaveyL Posts: 5,167
    iainf72 wrote:
    Garry H wrote:

    Agreed, Floyd was caught with synthetic testosterone. When's the judgement out on him? Thought it was June

    It's supposed to be June but it's looking unlikely.

    I know everyone says it's different but Landis' argument is that what has been called a positive for synthetic testosterone is not positive. And what this EPO study is showing is the vast differences which can occur in lab-land. So if one lab calls it positive and another doesn't, which is right? And he's been given even more of a fighting chance because his initial test performed poorly.

    Do we need a 3rd party to monitor WADA?

    As far as I know there was only one lab involved in testing Landis's samples.

    I would not read too much into the validity of other tests just because of this research on the epo test - the epo test, out of all the PED tests, is the one most open to interpretation. The IRMS test which nabbed Floyd for synthetic testosterone use is a whole different thing, and much more akin to what people imagine a scientific test to be, in terms of - you put a sanple in, it runs through a machine and you basically get a yes/no answer out.

    To reiterate, in Floyd's case the T/E ratio test was indeed performed in a sloppy manner. However that test is largely irrelevant as they have the IRMS test (and a longitudinal proifle). You don't even need to do a T/E test (and indeed I think with Justin Gatlin they may have gone direct to IRMS) for a conviction, so I would not expect Floyd to get off.
    Le Blaireau (1)
  • DaveyLDaveyL Posts: 5,167

    Article link. (you have to wait for the nice Ralph Lauren/Wimbledon advert to play. :wink): :-
    http://www.nytimes.com/2008/06/26/sport ... 12wq//b7LA)

    I meant I was going to look for the original research paper. I guess that won't have a Ralph Lauren advert! :D
    Le Blaireau (1)
  • iainf72iainf72 Posts: 15,784
    DaveyL wrote:

    To reiterate, in Floyd's case the T/E ratio test was indeed performed in a sloppy manner. However that test is largely irrelevant as they have the IRMS test (and a longitudinal proifle). You don't even need to do a T/E test (and indeed I think with Justin Gatlin they may have gone direct to IRMS) for a conviction, so I would not expect Floyd to get off.

    Could a poorly performance IRMS test yield an inaccurate result?

    If the answer is yes, then if they can introduce enough evidence to show it wasn't done correctly can you trust the result of the test? Landaluze got off because the same person worked on his A and B samples. Funnily, the same person worked on Floyds A and B samples.

    It would be better if a computer could make The Red Bulb Of Doom switch on when a sample was positive.
    Fckin' Quintana … that creep can roll, man.
  • DaveyLDaveyL Posts: 5,167
    iainf72 wrote:

    Could a poorly performance IRMS test yield an inaccurate result?

    I'm not an expert, but I doubt it - you'd either get rubbish out, or the correct answer, if you see what I mean. Having said that it should be possible to look up studies on false positives with IRMS, to see if that's been looked at. The test has been around for a while.

    Didn't censored Pound take his big red button of doom with him when he left office?
    Le Blaireau (1)
  • DaveyLDaveyL Posts: 5,167
    PS Sure, Landis could get off on such a technicality (as the same person working on A and B samples) - but he ain't gettin' off by casting doubt on the science, I would suggest.
    Le Blaireau (1)
  • DaveyLDaveyL Posts: 5,167
    Have had a look at the original paper now. I would not say there is much news in the low number of positives - I think people know the test is only really effective for a day or two after Epo administration. What is reassuring is that Lab A called all the samples positive during the "boost phase" (Lab B got no positives). After that, positives became a lot more sporadic for Lab A during the "maintenance phase", but Lab B still failed to pick up any positives. Obviously then, the big thing to take from this paper, by a country mile, is that one of the labs seems to be doing relatively OK in calling positives (given the limitations of the test) whereas the other did not find any positives at all. It's a big issue because these are both supposedly WADA accredited labs! One could be cheeky and suggest Lab A is the LNDD lab, and Lab B is the one on Belgium, based on what happened in the Mayo case!

    Since this has generated a bit of publicity, I would suggest WADA ought now to be banging some heads together at these labs, maybe sending a troubleshooter from Lab A over to sort out Lab B. I can imagine some questions are being asked at Lab B...

    The paper concludes by questioning whether more money should be invested in this test, or whether we should be looking for another test, and concludes with something of an endorsement for the bio-passport scheme:

    "The potential implementation of the blood passport where longitudinal monitoring will be used to identify changes indicative of doping practices seems to surpass many of the above problems."

    In recent years it's become possible to do mass spectrometry on large molecules like proteins, so I'm wondering if we'll see an Epo variant of the isotope ratio mass spec test that's used for synthetic testosterone. I'm not sure if the carbon isotopes of natural Epo and the recombinant stuff that athletes use is different though - need to look into that. Anyway even standard mass spec might also work - not sure of the cost though, it might be prohibitive.

    As for the performance gains in this study - everyone knows Epo gives you a huge performance gain so that's not news etiher. But as for the 50% gain at sub-maximal exercise - bear in mind there were only 8 subjects in this test, and none of them were what we would call athletes. Would you be confident in the results of a pharma company's clinical trials if they were done on only 8 volunteers? This to me seems to be the big drawback in a lot of sports science/exercise physiology papers - the trials are often done on fairly small groups of volunteers (for often understandable reasons).
    Le Blaireau (1)
  • iainf72iainf72 Posts: 15,784
    DaveyL wrote:
    PS Sure, Landis could get off on such a technicality (as the same person working on A and B samples) - but he ain't gettin' off by casting doubt on the science, I would suggest.

    As I've boringly said before, dope testing is a technical process so everything is a technicality :P
    Fckin' Quintana … that creep can roll, man.
  • DaveyLDaveyL Posts: 5,167
    I would calling bringing into question the science behind the IRMS test slightly more than a technicality. :D
    Le Blaireau (1)
  • iainf72iainf72 Posts: 15,784
    DaveyL wrote:
    I would calling bringing into question the science behind the IRMS test slightly more than a technicality. :D

    One of the Landis defense guys was an IRMS expert I believe.

    http://trustbut.blogspot.com/2007/05/he ... rning.html
    Fckin' Quintana … that creep can roll, man.
  • DaveyLDaveyL Posts: 5,167
    Bump.

    Ahem.
    Le Blaireau (1)
  • iainf72iainf72 Posts: 15,784
    Some more analysis with that cat from ACE here
    Fckin' Quintana … that creep can roll, man.
  • guv001guv001 Posts: 688
    If they can't catch you then you have done nothing wrong !!! Innocent until proven guilty.
  • I thought EPO doping was detected by measuring abnormally high heamatocrit levels, not from a urine test...?

    I'll go sit at the back of class... :roll:
  • dave_1dave_1 Posts: 9,512
    I thought EPO doping was detected by measuring abnormally high heamatocrit levels, not from a urine test...?

    I'll go sit at the back of class... :roll:

    an electrical charge, the shape of that charge in urine samples shows I understand signs of difference between endogenous and exogenous EPO...and above 80% isoforms-the electrical charge is considered very abnormal...anyone with 0% has probably neutralised their sample with persil. It's claimed Armstrong was 100% isoforms at 1999 TDF prologue if you believe the shower that did him up at L'equipe on 05 and the 6 so called positives show his isforms rose above 80% pn , funnily enough...the mountain stages of 99TDF and negative on the other stages...but do we believe?
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