Impey cleared of doping - free to race

[mrhender]

It makes perfect sense. Not as bad as JADCO, but starved for resources to the point they cannot afford to defend a sanction.

I've posted repeatedly that anti-doping agencies are incredibly weak and that this is by design. Do you believe me now?

That's not an implied opinion on Impey's innocence/guilt.

I know you have, and to my memory I have never claimed you wrong..
I Must admit that I was a bit surprised that they would try to pull it of in such an amateuric way.. Which leads me to the opening phrase of the article:

With South Africa desperately in need of sporting heroes, Impey was a consistent performer in an unforgiving sport where a few seconds divide those bathed in glory and those whose names history will not record.

Impey’s legacy, as the first African to wear the famed yellow jersey in last year’s Tour de France, will be imprinted in history, bringing glory to himself and his country.

On another note.. Could these procedural errors be deliberate?
Hmm... (not claiming guilty/innocence either here)

How could they think that no-one would look into this..
I called SAIDS in-experinced early on in this thread, they are starting to look just like that. If not worse.....

EDIT: I do believe you... Just to be clear...

 

[DirtyWorks]

How could they think that no-one would look into this..
I called SAIDS in-experinced early on in this thread, they are starting to look just like that. If not worse.....

A bunch of anonymous people in some Internet forum examining the facts is no problem. If it ever gets too controversial, we're just a bunch of conspiracy theorists who don't understand sports administration.

Much of the anti-doping system appears to be operated by sufficiently professional people without resources and very little political support to actually reign in doping. We don't know the details about why SAIDS is letting this one go, only that they are. Maybe some more facts will be published to clarify the situation.

If you go to the top of WADA, Reedie, he's shown his hand as a propaganda generator for the IOC.

 

[blackcat]

It makes perfect sense. Not as bad as JADCO, but starved for resources to the point they cannot afford to defend a sanction.

I've posted repeatedly that anti-doping agencies are incredibly weak and that this is by design. Do you believe me now?

That's not an implied opinion on Impey's innocence/guilt.

it is the model of enforcement well evolved by the SEC

 

[Merckx index]

That's a bombshell, thanks mrh.

I also found this very interesting:

This is highly unusual for a number of reasons. Probenecid is a rarely used drug nowadays; in fact few pharmacies even stock it.

Furthermore, for contamination to occur an uncoated version of the drug must be used in order to produce residue, or the drug must be cut or crushed. This is also rare.

So despite all the stories about how common contamination is in pharmacies, maybe it really isn’t?

Anyway, it’s hard to buy the alternative that the scientific case was so good that there was no way to challenge it. As Alex pointed out, a low level could result from contamination ingested the day of the test, or from a much larger, doping-level dose taken three days earlier. The latter scenario also mostly invalidates the point that no PE drugs were found with the probenecid. Depending on the drug, it might have been cleared to indetectable levels after three days. And as pointed out before, we don’t know what else they tested for.

I’m also wondering about Colonel’s claim that his positive was actually on a sample taken before the TT. Was he really tested both before and after? If he tested positive before, he should have tested positive after. Also, if he tested positive before the TT, it makes the contamination theory a little harder to support. If he was tested before the race, it must have been fairly soon after taking his pre-race capsules. That being the case, there might not have been time for enough of a low level contaminant to reach detectable levels in his urine.

E.g., if we assume the half-life is four hours, which seems to be the minimum estimate, only about 15% of probenecid in his blood would clear into the urine in an hour. For him to test positive at what I think is the minimum detectable level of 0.05 ug/ml, the ingested amount would have to be about 70 ug. To reach the minimum WADA sensitivity, it would be 350 ug. These are minimum estimates, assuming a four hour half life. If the half-life was longer—and in some studies with some individuals, it’s as high as 12 hours—the estimated amount ingested would have to be revised upward, to maybe 100-500 ug. Another upward revision would be required to take into account the fact that much of the drug would not be absorbed directly into his blood. Realistically, the ingested amount would probably have to be close to 1 mg. According to the study linked by fmk, 1 mg is probably pushing the limit of what contamination under the best circumstances would yield. All the more so if he didn’t take all the capsules before the race, but some during.

 

[keeponrollin]

Easy.

You cannot tell the difference.

Given clearing behaviors are well established you can plot back a curve. Anything on the curve is equally valid an assumption based on that detection level alone.

Exactly; & that's why strict liability exists as a policy; because otherwise it's almost always possible to obfuscate with a contamination defence.

 

[Granville57]

I also found this very interesting:

This is highly unusual for a number of reasons. Probenecid is a rarely used drug nowadays; in fact few pharmacies even stock it.

Furthermore, for contamination to occur an uncoated version of the drug must be used in order to produce residue, or the drug must be cut or crushed. This is also rare.

Indeed. I also found this very interesting:

[Shuaib] Manjra is a physician with extensive anti-doping experience.

The author exposes a number of elements behind this story, but doesn't stake their claim on one side of the fence or the other.

Impey's story seems to have some holes in it.

But also...

SAIDS may be at fault, and has been acting mostly out of self-interest while possibly concealing (or conveniently avoiding) those things that could be used against them by Impey.

It's all very curious indeed.

 

[Dear Wiggo]

Colonel: tested before the itt? This report says after.

"Further to the announcement of the Tour de France team and in the interests of full disclosure, I confirm that on 23 June 2014, I was notified by William Newman, the President of Cycling South Africa, about an adverse analytical finding for Probenecid following an in-competition test at the national time trial championships on 6 February 2014," Impey said.

http://http://www.cyclingnews.com/news/daryl-impey-tests-positive-for-probenecid

In-competition can be before the TT.

 

[Dear Wiggo]

I’m also wondering about Colonel’s claim that his positive was actually on a sample taken before the TT. Was he really tested both before and after? If he tested positive before, he should have tested positive after. Also, if he tested positive before the TT, it makes the contamination theory a little harder to support. If he was tested before the race, it must have been fairly soon after taking his pre-race capsules. That being the case, there might not have been time for enough of a low level contaminant to reach detectable levels in his urine.

E.g., if we assume the half-life is four hours, which seems to be the minimum estimate, only about 15% of probenecid in his blood would clear into the urine in an hour. For him to test positive at what I think is the minimum detectable level of 0.05 ug/ml, the ingested amount would have to be about 70 ug. To reach the minimum WADA sensitivity, it would be 350 ug. These are minimum estimates, assuming a four hour half life. If the half-life was longer—and in some studies with some individuals, it’s as high as 12 hours—the estimated amount ingested would have to be revised upward, to maybe 100-500 ug. Another upward revision would be required to take into account the fact that much of the drug would not be absorbed directly into his blood. Realistically, the ingested amount would probably have to be close to 1 mg. According to the study linked by fmk, 1 mg is probably pushing the limit of what contamination under the best circumstances would yield. All the more so if he didn’t take all the capsules before the race, but some during.

It depends on the protocol he was following to load up on bicarb. The gel caps seem to indicate he was doing it in-race, however you can load days before, apparently. Why you would need gel caps to do this is unknown, but in a case like this you can argue whatever you like, clearly.

 

[neineinei]

If an anti-doping authority is given a good enough explanation for the AAF the right thing to do is to drop the charges, call off the hearing and lift the provisional suspension of the athlete. If they/the tribunal have become convinced the athlete wasn't doping it will be a waste of time and recources to demand a hearing. A prolonged process isn't in the interest of the athlete.

WADA and UCI have the right to challenge the case regardless. There is an adverse analytical finding. If they think the case needs closer examination they can overrule SAIDS.

Impey have made a point of the fact that he and his lawyers/experts never had challanged the positive.

Whilst I never disputed the lab results and the finding, I was put in a very tough position of defending my case due to strict liability.

http://www.sport24.co.za/OtherSport/Cycling/South-Africa/Impey-cleared-of-doping-20140829

The Ludwick Mamabolo case no doubt was an embarasment to the SA Institute for Drug-Free Sport. A doper got away with it because they didn't do their job. This was in 2012/2013, and in fresh memory. All the more reason to do things right now.

When the positive from February was announced in July the delay was, at least in part, explained by the untimely death of a staff member at the WADA lab in Bloemfontein. The extra testing of the A-sample probably also had to do with the WADA lab, not SAIDS.

Saids chief executive Khalid Galant said the announcement was delayed owing to additional confirmation being required and the death of a staff member at the doping control laboratory in Bloemfontein.

http://www.iol.co.za/sport/cycling/impey-i-m-no-drug-cheat-1.1713522

 

[keeponrollin]

If an anti-doping authority is given a good enough explanation for the AAF the right thing to do is to drop the charges, call off the hearing and lift the provisional suspension of the athlete. If they/the tribunal have become convinced the athlete wasn't doping it will be a waste of time and recources to demand a hearing. A prolonged process isn't in the interest of the athlete.

NDAs shouldn't be dropping cases on the basis of things that are possible, or even, probable; & they certainly shouldn't be dropping them because they're convenient. Its chicken *** to kick them to WADA.

The only cases dropped this quickly should be clear cut cases, i.e. something like a National Doctor mis-prescribing a medication, & having a clear paper trail to prove the case.

 

[Colonel]

It depends on the protocol he was following to load up on bicarb. The gel caps seem to indicate he was doing it in-race, however you can load days before, apparently. Why you would need gel caps to do this is unknown, but in a case like this you can argue whatever you like, clearly.

That's a bombshell, thanks mrh.

I also found this very interesting:



So despite all the stories about how common contamination is in pharmacies, maybe it really isn’t?

Anyway, it’s hard to buy the alternative that the scientific case was so good that there was no way to challenge it. As Alex pointed out, a low level could result from contamination ingested the day of the test, or from a much larger, doping-level dose taken three days earlier. The latter scenario also mostly invalidates the point that no PE drugs were found with the probenecid. Depending on the drug, it might have been cleared to indetectable levels after three days. And as pointed out before, we don’t know what else they tested for.

I’m also wondering about Colonel’s claim that his positive was actually on a sample taken before the TT. Was he really tested both before and after? If he tested positive before, he should have tested positive after. Also, if he tested positive before the TT, it makes the contamination theory a little harder to support. If he was tested before the race, it must have been fairly soon after taking his pre-race capsules. That being the case, there might not have been time for enough of a low level contaminant to reach detectable levels in his urine.

E.g., if we assume the half-life is four hours, which seems to be the minimum estimate, only about 15% of probenecid in his blood would clear into the urine in an hour. For him to test positive at what I think is the minimum detectable level of 0.05 ug/ml, the ingested amount would have to be about 70 ug. To reach the minimum WADA sensitivity, it would be 350 ug. These are minimum estimates, assuming a four hour half life. If the half-life was longer—and in some studies with some individuals, it’s as high as 12 hours—the estimated amount ingested would have to be revised upward, to maybe 100-500 ug. Another upward revision would be required to take into account the fact that much of the drug would not be absorbed directly into his blood. Realistically, the ingested amount would probably have to be close to 1 mg. According to the study linked by fmk, 1 mg is probably pushing the limit of what contamination under the best circumstances would yield. All the more so if he didn’t take all the capsules before the race, but some during.

His TT start time was 7:57am and with the half life being 4 hours he could of taken it that night before bed expecting it to be out his system by morning of the TT should he podium and be tested. (+-9am) and not expecting a pre-race test. Chances were it wasnt "in and out" as normal and hence the trace amount in that sample but once the race was over it was out resulting in no positive for the remaining tests.

 

[Merckx index]

His TT start time was 7:57am and with the half life being 4 hours he could of taken it that night before bed expecting it to be out his system by morning of the TT should he podium and be tested. (+-9am) and not expecting a pre-race test. Chances were it wasnt "in and out" as normal and hence the trace amount in that sample but once the race was over it was out resulting in no positive for the remaining tests.

If he was doping with it, he would have had a detectable level after as well as before the TT. And presumably of some other substance he was using it in conjuction with.

I finally found the study I was looking for. This paper gives the renal clearance for probenecid as 0.6 – 0.8 ml/min. This refers to the volume of blood that contains the amount of drug appearing in the urine per unit of time. Knowing this, and the peak concentration of drug in the blood, one can calculate how much of a dose of probenecid appears in the urine per time.

For an oral dose of 250 mg, about 2 – 2.7 mg appears in the urine over a period of four hours, which corresponds to about the amount of urine that would be provided in one sample. This is about 1% of the dose. If the dose is increased, the % found in the urine in any given time period increases slightly, which means that if the dose were decreased below 250 mg, the % would be decreased. So 1% can be regarded as a maximum, in that for lower doses, such as contaminants, the % should be lower.

But if we use the 1% figure, we can apply it to Impey as follows: the minimum detectable dose seems to be about 0.05 ug/ml. In a typical 200 ml urine sample, this corresponds to a total of 10 ug. If this is 1% or less of the amount ingested, this means the latter must be at least 1 mg.

This is very high for a contaminant. In the article fmk linked to, the highest contaminant dose observed was about 200 ug/capsule, and even assuming this amount was on Impey’s capsules, some of it would be lost during handling. And I repeat, I’m using the most conservative estimates. The minimum sensitivity demanded by WADA is just 0.25 ug/ml, and for all we know, the amount Impey tested for may have been well above the minimum. And the % of the ingested amount in the urine of such a low dose would be expected to be less than 1%.

I really wonder, based on the similar Cielo case, if Impey’s experts may have simply demonstrated that his capsules were contaminated with probenecid, without showing that the amount present could have accounted for his positive. SAIDS might have felt that if any contamination were present, then one had to assume that was the cause of the positive. This is the way contaminated supplement cases generally work. I can understand the logic, except that one also wonders how easy it would have been to contaminate the capsules intentionally. One would have to know something about the drug to get the contamination level right—remember, this was the argument used by Ashenden against LA wrt the ’99 EPO samples—but knowing about the Cielo case, Impey could have just dusted the capsules and hoped for the best. In fact, if it turns out his level is too high to be accounted for by contamination, that would further suggest that he might have done that.

Hopefully, though, more details will eventually emerge. I hope they actually tested the idea with a known clean set of capsules. Beyond Impey's innocence or guilt, this should be done so that we can evaluate the seriousness of this problem for possible future cases.

Edit: I was able to access the first 3 pages, and one figure, in the above link. It confirmed, in a more quantitative way, what I had picked up from other studies--that very little unmetabolized probenecid appears in the urine. Most of the substance is excreted as probenecid glucuronide. If this is tested for, rather than probenecid itself, the sensitivity of the test will be greatly increased, and the amount needed to be ingested to get a level of 0.05 ug/ml can be reduced to about 40-50 ug. I've been uncertain about whether this is what is assayed in the test, because most studies I've seen refer to probenecid, not the glucuronide. But to maximize the sensitivity of the test, it would only make sense to assay the latter.

 

[fmk_RoI]

I hope they actually tested the idea with a known clean set of capsules.

It's a bit like calling in the guys from Mythbusters, which I thought the hardcore science geeks hated?

Seriously though, would they ever do that, or would they just rely on the math supported by published papers, same way you've been trying to calculate it? Auditable evidence.

 

[DirtyWorks]

Hopefully, though, more details will eventually emerge. I hope they actually tested the idea with a known clean set of capsules. Beyond Impey's innocence or guilt, this should be done so that we can evaluate the seriousness of this problem for possible future cases.

Another great post. Thank you.

As for testing the idea, it would be great if someone had the money, but it's just not how the system is set up.

The contamination defense has been used before with varying success. The last I recall was an Idiot Master's Fattie in California who tried to argue the substance was in the container as if someone on the production line was sprinkling PEDs in canisters of vitamin supplements. Thankfully, it didn't work.

 

[Catwhoorg]

You forgor Bruce Croall already ?

Contamination of a supplement, which was handily available for testing.

6 month ban only, which finished nicely in time for him to compete at the Commonwealth games.

 

[Race Radio]

Looking forward to the full decision but I think there is a good chance this will be appealed.

 

[zigmeister]

It depends on the protocol he was following to load up on bicarb. The gel caps seem to indicate he was doing it in-race, however you can load days before, apparently. Why you would need gel caps to do this is unknown, but in a case like this you can argue whatever you like, clearly.

"Apparently"???? It is science, there is no "apparently" of how to load the substance.

A simple search would yield many studies of athletes and the affects/methods of sodium bicarbonate on performance.

 

[blackcat]

"Apparently"???? It is science, there is no "apparently" of how to load the substance.

A simple search would yield many studies of athletes and the affects/methods of sodium bicarbonate on performance.

horses, thoroughbreds

 

[Tonton]

But if we use the 1% figure, we can apply it to Impey as follows: the minimum detectable dose seems to be about 0.05 ug/ml. In a typical 200 ml urine sample, this corresponds to a total of 10 ug. If this is 1% or less of the amount ingested, this means the latter must be at least 1 mg.

This is very high for a contaminant. In the article fmk linked to, the highest contaminant dose observed was about 200 ug/capsule, and even assuming this amount was on Impey’s capsules, some of it would be lost during handling. And I repeat, I’m using the most conservative estimates.

I really wonder, based on the similar Cielo case, if Impey’s experts may have simply demonstrated that his capsules were contaminated with probenecid, without showing that the amount present could have accounted for his positive. SAIDS might have felt that if any contamination were present, then one had to assume that was the cause of the positive.

Brilliant post. Am I correct then to assume that at this stage you would lean towards doping vs. bad luck?

 

[Dear Wiggo]

"Apparently"???? It is science, there is no "apparently" of how to load the substance.

A simple search would yield many studies of athletes and the affects/methods of sodium bicarbonate on performance.

Uh. Yes, it is apparently. If you are going to claim knowledge of every protocol for loading of any and every legal supplement then bully for you. The only protocol I had read about prior to this incident and the one that is being assumed in all the discussions to date in this thread has been acute loading.

I am now introducing a previously unstated protocol to the discussion - serial loading.

I notice that with all your pomp and ceremony you don't actually name any of these multiple protocols, or cite any papers, let alone link to them. Almost as if you were making it up, but never mind.

You clearly have a problem with me - I am still waiting for a reply in the other thread where you started to get personal with me for no apparent reason.

I suggest you check the vendetta at the door and try to interact civilly.

 

[Merckx index]

Brilliant post. Am I correct then to assume that at this stage you would lean towards doping vs. bad luck?

See my edit to that post. I initially assumed they tested for unmetabolized probenecid. That makes no sense, though, given that most of the drug is excreted in the form of several metabolites, and one in particular (probenecid glucuronide). The sensitivity of the test would be greatly improved by testing for that metabolite. I’ve been a little confused, though, because a study I cited previously as reporting what I think is the highest sensitivity for probenecid detection never mentioned that its concentration in the urine is far lower than that of the glucuronide. Some of the studies it cited also seemed to measure probenecid rather than the glucuronide.

However, I found a paper in which the glucuronide was tested, though without seeing the full paper I don't know what the sensitivity was. The abstract says the diuretics they examined could all be detected at 0.05 - .50 ug/ml, so at best they matched the 0.05 ug/ml reported by the previously cited paper. Assuming this is the case, the amount of contaminating probenecid necessary to result in a positive test can be reduced dramatically, perhaps to as low as 10-20 ug. I want to emphasize that this is based on simply extrapolating the results of studies using therapeutic doses of the drug to ingestion of a very small contaminating amount. In the latter case, the kinetics may be different, and extrapolation may not be accurate. But it’s all anyone can do, including any experts that Impey may have hired.

Ten-twenty micrograms is much more in line with what a reasonable amount of contamination might be, though I still think it would be important to test this with a pill counter. It would be simple enough to do. The most expensive and time-consuming part of the defense would be testing the capsules Impey had in his possession for probenecid. I assume they did this, and if they did, it would be easy enough to test some more capsules from a pill counter. As I said before, given that this case is likely to serve as a precedent to be cited by other athletes in the future, I really think the level of contamination possible needs to be addressed.

 

[DirtyWorks]

Ten-twenty micrograms is much more in line with what a reasonable amount of contamination might be, though I still think it would be important to test this with a pill counter. It would be simple enough to do. The most expensive and time-consuming part of the defense would be testing the capsules Impey had in his possession for probenecid. I assume they did this, and if they did, it would be easy enough to test some more capsules from a pill counter. As I said before, given that this case is likely to serve as a precedent to be cited by other athletes in the future, I really think the level of contamination possible needs to be addressed.

Don't assume. The burden would have been on Impey to pay for a test to provide evidence, not the NADO or anti-doping authority.

I totally agree it would be compelling evidence, but the anti-doping authority decided they had all the evidence they needed.

Again, thank you for spending time on this topic. It's invaluable.

 

[Granville57]

Is there anything in the official releases thus far that claim which method Impey used to actually fill his own capsules?

It seems a rather tedious process. I've seen some low-priced methods, but I'm just curious as to what methods an experienced pro athlete, whose career apparently depends on home-made pills , would employ to get all that powder into those tiny little capsules.

From what I've observed, it seems that the process of filling empty capsules, and the devices commonly used, would only help to (inadvertently at least) reduce the amount of any residue that might be found on the outside of such capsules.

But then who's to say that contamination couldn't occur during the loading process?
And what would that tell us?

As far as I know, this hasn't been addressed yet.
Impey may have received contaminated empty gel caps, but then what happened?
The bicarb doesn't get in there by itself.

 

[Catwhoorg]

There are devices (actually look similar to pill counters) that are used for small scale capsule filling.

An example would be someone who makes their own herbal remedy capsules for example.

Still have to fit the two halves together which is pretty tedious.

 

[senatorrick]

There are devices (actually look similar to pill counters) that are used for small scale capsule filling.

An example would be someone who makes their own herbal remedy capsules for example.

Still have to fit the two halves together which is pretty tedious.

Yes his story is definitely original !! Can't wait till the game is uprf again