All About Salbutamol

[gillan1969]

here's what UCI say

"The UCI has considered all the relevant evidence in detail (in consultation with its own experts and experts from WADA). On 28 June 2018, WADA informed the UCI that it would accept, based on the specific facts of the case, that Mr Froome’s sample results do not constitute an AAF. In light of WADA’s unparalleled access to information and authorship of the salbutamol regime, the UCI has decided, based on WADA’s position, to close the proceedings against Mr Froome."

Here's what WADA say

"On 2 July 2018, the World Anti-Doping Agency (WADA) announced that it would not be appealing the Union Cycliste Internationale’s (UCI’s) decision not to assert an Anti-Doping Rule Violation (ADRV) in the case involving British rider Christopher Froome."

"While WADA remains convinced that the UCI reached the right and fair outcome on this very complex case...."

so UCI say its WADA and WADA say its UCI....in fairness it's looking like WADA.......WADA in effect they won't back up UCIO at CAS and will side with Froome...UCI has to call it a day

WADA conclusion based on Froomes Vuelta data....we need to see Froome's Vuelta data....simples

 

[Merckx index]

In some other cases, athletes have been able to demonstrate an unusually high salbutamol excretion by conducting a controlled pharmacokinetic study (CPKS). It was accepted by the UCI, however, that in this case such a study would not have provided reliable evidence as it would be impossible to adequately recreate similar conditions to when Mr. Froome was subjected to the test, taking into account his physical condition, which included an illness, exacerbated asthmatic symptoms, dose escalation over a short period of time, dehydration and the fact that he was midway through a multi-day road cycling race.

But in its own statement, UCI specifically ruled out illness as relevant. That leaves riding in a GT and dehydration as the only reasons for not performing a CPKS, which again, are factors in many AAFs. Nothing unique about those factors at all.

In order to stay on top of this complex area of anti-doping, and as outlined in the background document on salbutamol linked below, WADA has funded and supported a number of salbutamol studies over the years and continues to do so. Below is an extensive list of publications originating from WADA-sponsored studies related to salbutamol excretion as WADA encourages research teams to publish the results of their studios in peer-reviewed journals. (There have also been published studies, not sponsored by WADA, that have provided useful data.)

• Sporer, Sheel & McKenzie, Med Sci Sport Exerc 2008, 40:149
• Sporer, Sheel, Taunton, Rupert & McKenzie, Clin J Sports Med 2008 18:282.
• Mareck, Guddat, Schwenke, Beuck, Geyer, Flenker, Elers, Backer, Thevis & Schanzer, Drug Test Analysis, 2011, 3:820
• Elers, Morkeberg, Jansen, Belhage, Backer, Scan J Sport Med 2012b: 22: 232–239
• Dickinson, Hu, Chester, Loosemore & Whyte. Clin J Sport Med. 2014, 24:482
• Elers, Pedersen, Henninge, Hemmersbach, Dalhoff & Backer, Int J Sport Med 2011, 32:574
• Elers, Pedersen, Henninge, Hemmersbach, Dalhoff & Backer, Clin J Sport Med 2012, 22:140
• Dickinson, Hu, Chester, Loosemore & Whyte, J Sport Sci Med, 2014, 13:271
• Dickinson, Hu, Chester, Loosemore & Whyte, Clin J Sport Med 2014, 24:482
• Haase, Backer, Kalsen, Rzeppa, Hemmersbach & Hostrup, Drug Test Analysis 2016, 8:613
• Hostrup, Kansel, Auchenberg, Rzeppa, Hemmersbach, Bangbo & Backer, Drug Testing Analysis 2014 6:528 (final abstract is pending)

The references in bold are the studies in which 800 ug was tested. All the others used higher doses, except the last, which hasn’t been published yet. Note also that one of the Dickinson references is repeated on the list. I hope WADA took a little more care in coming to its decision.

Of those studies in bold, there were a total of 187 samples, out of which only three (1.6%) exceeded 1000 ng/ml. Furthermore, only one sample exceeded the decision limit of 1200 ng. This was a corrected value, which was increased from the uncorrected value because of dilute urine, that is, the USG was < 1.020. Since the new rules specify that an athlete’s sample does not have use the corrected value if it raises the effective salbutamol concentration, this value would not have resulted in an AAF. In fact, none of the nearly two hundred samples would have.

So there are no published studies I’m aware of—and apparently, that WADA is aware of-- in which a subject inhaled 800 ug and reached Froome’s level. (Other than the Swiss runner, who technically took more than 800 ug, and clearly was a very unusual case).

Also, while WADA has repeatedly implied that intense exercise and dehydration can affect the urinary levels, several of the studies in bold examined these factors, and found no evidence for a significant effect. For example, in one of the Dickinson studies, 32 subjects exercised until they lost either 2% or 5% of their body mass. In the other study, 7 subjects performed a 5 km run. None of the more than 70 total samples exceeded 1000 ng/ml.

In April, WADA requested to intervene in the UCI proceedings as a third party so as to meet any challenge to the salbutamol regime but its request was denied by the UCI Tribunal.

The key word here is "Tribunal". It wasn't UCI that refused, it was Haas. Why? WADA doesn't say, but maybe he didn't want another party complicating the proceedings. He may have already decided that he wasn't going to accept any challenge to the salbutamol threshold--I believe in fact he played a key role in creating it?--so WADA's participation was unnecessary.

It should be noted that, until WADA received Mr. Froome’s detailed explanations on 4 June, WADA considered that this case merited going through a CPKS and, if necessary, disciplinary proceedings at both the UCI and Court of Arbitration for Sport level.

So the decision not to require a CPKS was made long after Froome would have been asked to provide one. This would have been in January or February, and his refusal or inability to do such a study was no doubt a contributing factor in UCI's decision to propose a ban, and send the case to the Tribunal. If any more evidence were necessary, this makes it clear that Froome's case is unique in the annals of anti-doping cases.

However, based on what was provided by UCI to WADA, and once Mr. Froome’s explanations were assessed by the appropriate internal and external experts, it became clear to WADA that, in particular, the combination of his within-subject variability for salbutamol excretion, the sudden and significant increase in salbutamol dosage prior to the doping control, and the number of consecutive doping controls meant that the analytical result could not be considered inconsistent with the ingestion of a permissible dose of inhaled salbutamol.

The computer simulation model, which we don't get to see, because WADA/UCI/Froome are chicken-*** to let the wider scientific community evaluate it.

At present, there is no evidence that a change to the threshold or decision limit for salbutamol is required.

Because of the literature cited above. Note also that while WADA has referred to unpublished studies, their statement here basically reinforces the conclusion that these unpublished studies don't change anything. It all comes down to Froome's unique conditions, even though these conditions were not in fact unique.

 

[topcat]

Agreed. Now we have confirmation that the decision was *** (for want of a better word).

 

[jmdirt]

If the UCI would have been the only body involved I would call BS, but WADA, they would love to bust a dirty cyclist to prove their worth. The UCI is bind, WADA is blind, if there was a neutral third party, they would be blind...

 

[Benotti69]

Re:

If the UCI would have been the only body involved I would call BS, but WADA, they would love to bust a dirty cyclist to prove their worth. The UCI is bind, WADA is blind, if there was a neutral third party, they would be blind...

Nope. WADA could bust loads of big names to prove its worth. It is not in the job of dragging sport through the dirt.

Hell, WADA could do lots more for clean sport, but that is not why it was set up. It is a smoke screen.

As Topcat said. ***.

 

[Benotti69]

http://fasterskier.com/fsarticle/fis-rules-and-keeping-quiet-why-you-didnt-hear-about-sundby-sooner/

mong athletes and fans, one of the biggest reactions was of surprise: Sundby’s samples had been collected in December 2014 and January 2015, yet the case had never been publicized.

That is primarily because despite the adverse analytical finding (AAF) of salbutamol — a common asthma medication — in two of Sundby’s urine samples, the International Ski Federation (FIS) concluded that he had not broken any rules.

Sundby’s urine samples both had over 1300 ng/mL of salbutamol, triggering an AAF and beginning the investigative process into whether he had an appropriate TUE.

The reason — that he was taking the medication through a nebulizer rather than an inhaler and believed that this made a TUE unnessecary

Froome claims he only took puffs. Sundy used a nebuliser and still only showed a level of 1300ng/ml. No way Froome reached his 2000 level on puffs.

 

[Merckx index]

Re: Re:

Nope. WADA could bust loads of big names to prove its worth. It is not in the job of dragging sport through the dirt.

Hell, WADA could do lots more for clean sport, but that is not why it was set up. It is a smoke screen.

As Topcat said. ***.

I don’t think it’s quite that simple. They weren’t afraid to go after Contador, even after his fed had cleared him.

Considering that change from May 15 to June 28, it has crossed my mind that there might have been a deal, at least implicit if not explicit: We will drop the case if you promise not to make a big deal claiming that the salbutamol threshold needs to be changed. Because there could be a lot of lawsuits if the threshold were seriously challenged. I really don't understand why Petacchi isn't suing over the new USG rule. I know it's a general legal principle that you can't have court decisions reversed because of later changes in the law, but in civil and criminal cases it can be argued that the law changed because of new conditions that didn’t exist previously. That isn’t the case here. There has been no new research supporting the USG correction. The rationale for it is the same as it was during Petacchi's case.

Anyway, WADA is walking a very fine line here. On the one hand, they're insisting that the threshold is fine. On the other hand, they have to explain why, that being the case, Froome was not sanctioned.

I think this is why they made public the eight other AAFs that were exonerated in the past five years. The threshold is OK, they’re saying, because though it may be breached on rare occasion by an innocent athlete, a closer examination will clear him. This is part of their strategy for showing the current threshold is compatible with an occasional AAF of an innocent rider.

The other part is arguing that Froome rode under unique conditions, though it seems quite clear he didn't. They keep hammering away at how special Froome's situation was, even as UCI has denied that illness or other medications made any difference. Now I notice that WADA has thrown in exacerbated asthma, though there is no evidence that would affect urinary levels, either. Good luck trying to show that, either in the lab or on the road. In fact, you would expect that other athletes have upped their dosages when they’ve had a serious asthma attack, and thus would be more likely to get an AAF then, rather than when they were inhaling only occasionally.

The one thing WADA doesn’t want to suggest is that Froome has a unique physiology. Because that would imply a get-out-of-jail-free card not just now, but in the future. If he were ever to exceed the limit again, he could just say, it's already been proven that I'm the rare individual that can exceed the limit within the allowed amount. Asked and answered.

 

[Benotti69]

Re: Re:

Nope. WADA could bust loads of big names to prove its worth. It is not in the job of dragging sport through the dirt.

Hell, WADA could do lots more for clean sport, but that is not why it was set up. It is a smoke screen.

As Topcat said. ***.

I don’t think it’s quite that simple. They weren’t afraid to go after Contador, even after his fed had cleared him.

Considering that change from May 15 to June 28, it has crossed my mind that there might have been a deal, at least implicit if not explicit: We will drop the case if you promise not to make a big deal claiming that the salbutamol threshold needs to be changed. Because there could be a lot of lawsuits if the threshold were seriously challenged. I really don't understand why Petacchi isn't suing over the new USG rule. I know it's a general legal principle that you can't have court decisions reversed because of later changes in the law, but in civil and criminal cases it can be argued that the law changed because of new conditions that didn’t exist previously. That isn’t the case here. There has been no new research supporting the USG correction. The rationale for it is the same as it was during Petacchi's case.

Anyway, WADA is walking a very fine line here. On the one hand, they're insisting that the threshold is fine. On the other hand, they have to explain why, that being the case, Froome was not sanctioned.

I think this is why they made public the eight other AAFs that were exonerated in the past five years. That's part of their evidence that other athletes have had special cases, and were able to convince WADA they didn't inhale more than the allowed amount. The threshold is OK, they’re saying, because though it may be breached on rare occasion by an innocent athlete, a closer examination will clear him.

The other part is arguing that Froome rode under unique conditions, though it seems quite clear he didn't. They keep hammering away at how special Froome's situation was, even as UCI has denied that illness or other medications made any difference. Now I notice that WADA has thrown in exacerbated asthma, though there is no evidence that would affect urinary levels, either. Good luck trying to show that, either in the lab or on the road. In fact, you would expect that other athletes have upped their dosages when they’ve had a serious asthma attack, and thus would be more likely to get an AAF then, rather than when they were inhaling only occasionally.

The one thing WADA doesn’t want to suggest is that Froome has a unique physiology. Because that would imply a get-out-of-jail-free card not just now, but in the future. If he were ever to exceed the limit again, he could just say, it's already been proven that I'm the rare individual that can exceed the limit within the allowed amount. Asked and answered.

WADA have opened the flood gates with Froome. Anyone with a sponsor/s willing to spend $$$s to protect their athletes will take WADA to task and will win. If they lose at CAS they could still go the civil courts as this has set a precendence.

I think behind the scenes in the administration of Sport there are politics at play. Why did they bust Contador? Did they do it for Lance, Nike, etc....Did they bust Contador becuase the Spanish bust Fuentes? Who knows the real reasons? Why let Froome off any obvious AAF? None of it, imo, is for sporting reasons.

 

[thehog]

Re: Re:

Nope. WADA could bust loads of big names to prove its worth. It is not in the job of dragging sport through the dirt.

Hell, WADA could do lots more for clean sport, but that is not why it was set up. It is a smoke screen.

As Topcat said. ***.

I don’t think it’s quite that simple. They weren’t afraid to go after Contador, even after his fed had cleared him.

Considering that change from May 15 to June 28, it has crossed my mind that there might have been a deal, at least implicit if not explicit: We will drop the case if you promise not to make a big deal claiming that the salbutamol threshold needs to be changed. Because there could be a lot of lawsuits if the threshold were seriously challenged. I really don't understand why Petacchi isn't suing over the new USG rule. I know it's a general legal principle that you can't have court decisions reversed because of later changes in the law, but in civil and criminal cases it can be argued that the law changed because of new conditions that didn’t exist previously. That isn’t the case here. There has been no new research supporting the USG correction. The rationale for it is the same as it was during Petacchi's case.

Anyway, WADA is walking a very fine line here. On the one hand, they're insisting that the threshold is fine. On the other hand, they have to explain why, that being the case, Froome was not sanctioned.

I think this is why they made public the eight other AAFs that were exonerated in the past five years. That's part of their evidence that other athletes have had special cases, and were able to convince WADA they didn't inhale more than the allowed amount. The threshold is OK, they’re saying, because though it may be breached on rare occasion by an innocent athlete, a closer examination will clear him.

The other part is arguing that Froome rode under unique conditions, though it seems quite clear he didn't. They keep hammering away at how special Froome's situation was, even as UCI has denied that illness or other medications made any difference. Now I notice that WADA has thrown in exacerbated asthma, though there is no evidence that would affect urinary levels, either. Good luck trying to show that, either in the lab or on the road. In fact, you would expect that other athletes have upped their dosages when they’ve had a serious asthma attack, and thus would be more likely to get an AAF then, rather than when they were inhaling only occasionally.

The one thing WADA doesn’t want to suggest is that Froome has a unique physiology. Because that would imply a get-out-of-jail-free card not just now, but in the future. If he were ever to exceed the limit again, he could just say, it's already been proven that I'm the rare individual that can exceed the limit within the allowed amount. Asked and answered.

WADA have opened the flood gates with Froome. Anyone with a sponsor/s willing to spend $$$s to protect their athletes will take WADA to task and will win. If they lose at CAS they could still go the civil courts as this has set a precendence.

I think behind the scenes in the administration of Sport there are politics at play. Why did they bust Contador? Did they do it for Lance, Nike, etc....Did they bust Contador becuase the Spanish bust Fuentes? Who knows the real reasons? Why let Froome off any obvious AAF? None of it, imo, is for sporting reasons.

You really can’t go to civil courts. You need some form of civil infringement to sue through tort law. No civil court will set precedence on a sports case if it falls in line with sports law, none. The European Court can be used if your civil rights have been violated but there is very little room to those regards, some have tried. Unless you just want to the other side to burn up bunch of cash and be exposed to discovery then sue otherwise there is little point.

 

[thehog]

Point in case, the Heras judgment. Means jack *** and nothing changed.

 

[thehog]

Re: Re:

Nope. WADA could bust loads of big names to prove its worth. It is not in the job of dragging sport through the dirt.

Hell, WADA could do lots more for clean sport, but that is not why it was set up. It is a smoke screen.

As Topcat said. ***.

Considering that change from May 15 to June 28, it has crossed my mind that there might have been a deal, at least implicit if not explicit: We will drop the case if you promise not to make a big deal claiming that the salbutamol threshold needs to be changed. Because there could be a lot of lawsuits if the threshold were seriously challenged. I really don't understand why Petacchi isn't suing over the new USG rule. I know it's a general legal principle that you can't have court decisions reversed because of later changes in the law, but in civil and criminal cases it can be argued that the law changed because of new conditions that didn’t exist previously. That isn’t the case here. There has been no new research supporting the USG correction. The rationale for it is the same as it was during Petacchi's case.

The change was ASO wrote to Sky 3 weeks before the Tour started stating they were going to exclude him. That applied the pressure on WADA (not to mention Sky pressuring all sides) to force the UCIs hand.

Then WADA and the UCI ran from the crime scene saying it had nothing to do with them. A dead body, Froome holding gun but found innocent.

 

[Merckx index]

We now have some idea of the key events. In late January, Froome’s team sent some requests for information to WADA. They didn’t reply until early March, leading some to conclude that it wasn’t Froome who delayed the proceedings. Why did WADA take so long? Because Froome’s team had raised the possibility of challenging the salbutamol threshold. WADA probably consulted with their lawyers as well as their scientists. They wanted to be very sure of what they were doing.

About a month later, in April, WADA told UCI they were willing to join them, in order to defend the salbutamol threshold. This is evidence that WADA was still concerned that Froome’s team would challenge the threshold. By that time, Haas had been appointed in charge of the Tribunal, and he refused. Why? As I said before, I think because he was not going to admit questions about the threshold into the proceedings. He felt that had been adequately justified, and the defense was just fishing. If he felt otherwise, I don’t know how he could have possibly justified excluding WADA.

In the middle of May, WADA, perhaps wanting to be sure the threshold wouldn’t be challenged, sent more information to Froome’s team. This seems to have been initiated at their end, not in response to anything more Froome had requested. At this point, WADA was still siding with UCI in believing Froome had no satisfactory explanation. Froome then replied on June 4, with the documents that apparently changed WADA’s mind.

What happened? In April, Heuberger et al published their paper claiming that their model predicted a very high level of false positives. While UCI in one of its early statements said that that model did not figure into the Froome decision, I suspect it did, in two ways. First, it gave Froome’s team the idea of using simulations to estimate the probability of exceeding the threshold. Though this is not a new idea in pharmacology, it may have only occurred then to his scientific team that they could use the same general approach, but employing Froome’s Vuelta samples. And second, the Heuberger paper emphasized that peak salbutamol urinary concentrations occur within one hour of inhaling. So the team would have realized that the way of maximizing the probability of exceeding the threshold would be to maintain that Froome took the maximum allowed dose all very soon before providing the urine sample after stage 18. They would contrast this with the other stages, where they would argue he not only took a much lower dose, but long before the end of the stage, and perhaps urinating in between. Since the stage 18 level was far above any of the other tested levels, it was important to show that what happened on that day was very different from what happened on every other day.

Still, it’s hard for me to believe that that argument carried the day. Did WADA’s scientists really buy it? If so, why didn’t UCI’s scientists, since nothing in the UCI statement suggests that they came to the same conclusion independently? If WADA’s scientists didn’t buy it, why did WADA drop the case?

Maybe because all the other options looked worse? There’s no indication that Haas was going to issue a ruling before the Tour; as far as we know, there hadn’t even been a hearing, though one isn’t required. If WADA hadn’t acted, Froome would either have been banned from the Tour—with a very messy legal situation that ASO probably would have lost—or he would have ridden under a cloud. If the decision had been issued after the Tour, he might have been stripped of his results, confirming what all the critics of the delay had been predicting all along; or been allowed to keep both the Giro and the Tour, which would have been a near-complete victory for him, and made it look as though he was allowed to delay until both races were done. If Haas had ruled in favor of Froome, and WADA had appealed, they would have been seen by many as the ones responsible for delaying for months the official status of the results. The public had already been stewing for months over what seemed to be taking an inordinate amount of time. Now WADA was going to make everyone wait a lot longer?

At least when WADA and UCI appealed the Contador decision, it was well before the Giro. While Contador had a right to ride, he entered knowing he might lose his results. There was no pressure as I recall to ban him from the race, and if WADA had suddenly wanted to back out, it would have been very difficult for them to rationalize it.

Maybe this is not the explanation. Maybe Froome’s team made a convincing case. But a lot of us won’t buy that until/unless they release more information. The urinary values for all of Froome’s Vuelta samples would be a good place to start. WADA/UCI could also ask the eight other exonerated athletes to allow their decisions to be published. What ever happened to that old saying, If you're innocent, you have nothing to hide?

Edit: Something just occurred to me—I wonder if any of those high-powered pharmacologists at WADA or on Froome ‘s team thought about this. According to one (unconfirmed) report, the model predicted 10% of samples would exceed the threshold or limit. If that were true, then when testing the perhaps hundreds of samples that have been provided by athletes that inhaled 800 ug, there would be certain to be several or more false positives, and this would not be acceptable. You could not have a test with this high a rate of false positives applied to a population.

But the model Froome’s test used apparently was created from only his own samples, and applies only to him. It’s not intended for anyone else (because of those “unique conditions”, remember?). And for him alone, a 10% probability of a false positive should be acceptable. It means there is a 90% chance that the positive is genuine, i.e., resulted from taking more than allowed amount. The standard for judging doping cases is between preponderance of evidence—more than 50% probability—and beyond reasonable doubt, which might be considered > 95%, or perhaps 99%. So a 90% probability that Froome did exceed the allowed amount ought to be enough to warrant a sanction.

Froome’s supporters have been crowing about how the Glaxo model allows Froome to avoid considering laboratory results, and only focus on himself. But the downside of that approach is that the acceptable level of false positives is much higher than it would be for a large pool of subjects. If you’re going to argue that you are unique, you can’t appeal to the crowd when determining standards of probability.

The rebuttal, I suppose, would be that while there was only a 10% chance he was within the allowed amount, this would be greater than the probability that he intentionally doped. That seems to be one of the other arguments WADA/UCI used. But what about the probability that he accidentally or on purpose took more than the allowed amount?

 

[samhocking]

It means there is a 90% chance that the positive is genuine

Twisting a 10% false positive simulation model also being 90% true positive is ambiguous is it not? Surely the 10% false positive model simulation was based on the the allowed max amount was inhaled and within limits, not illegal amounts that would be required to suggest the other 90% were true positive in Froomes own data?

 

[topcat]

To contribute anything to this thread, one needs at least a basic knowledge of science, logic and probability.

 

[Mamil]

Medical science is not my forte, but common sense and logic tells me that if a rider like Froome, who must have been tested hundreds of times over the last 6 years, has never previously tested over the salbuatmol threshold, let alone record a result double the limit, despite supposedly taking the drug consistently for years, then the chances of his body producing such a result without him exceeding the maximum allowed dosage on that day must be infinitely small. Almost impossible. All the 'clever' journal articles and studies in the world will not convince me otherwise.

Since it is also highly unlikely that a team as organised as Sky and a rider as meticulous as Froome was so silly as to simply take a few too many puffs, then it follows that the whole 'how many puffs' question is simple misdirection and largely irrelevant. The amount of the drug in his system, and the causes of the stuff up leading to such a high amount, surely lie elsewhere.

Which is why for me so much of what has been released regarding the reasoning for the 'no AAF' decision, from the importance placed on Froome's self-reported dosages during the Vuelta, to the bizarre 'why would he dope?' argument, simply convince me that WADA lost the will or interest to pursue the case properly. Not because of the 'science', but due to political and/or financial considerations.

 

[Merckx index]

Re:

It means there is a 90% chance that the positive is genuine

Twisting a 10% false positive simulation model also being 90% true positive is ambiguous is it not? Surely the 10% false positive model simulation was based on the the allowed max amount was inhaled and within limits, not illegal amounts that would be required to suggest the other 90% were true positive in Froomes own data?

The probability of a false positive + that of a genuine positive by definition = 100%. Saying there is a 10% chance of a false positive means there is a probability of 90% of a genuine positive.

The issue concerns the acceptable probability of a false positive. As I said, for a standard doping test, 10% is far too high, because the test will be applied to thousands of athletes, resulting in about 10% x the number tested. That's not the case with salbutamol, because a) the number of athletes who have asthma is probably < 10% of all athletes; and b) the 10% only refers to athletes taking 800 ug shortly before being tested. So even if this model is correct, the number of actual false positives would be quite low. And the stats bear that out--very few AAFs.

However, 10% is still far too high, because WADA can't assume athletes usually will not take 800 ug. As long as they're allowed to, one has to assume the worst case, that they're always taking that much. That's only fair.

All of what I've just said applies to a test applied to a large population. But Froome's model only applies to him. It's not intended to apply to others. If it did, and WADA accepted the conclusion, they would be forced to change the theshold. The 10% false positive rate rate (assuming they really found that high a figure, which I doubt) refers to the chances of Froome--only he--exceeding the threshold or limit if he took 800 ug. And in those circumstances, 10% ought to low enough. It means the odds that he took the allowed amount are about 10:1. Not very likely.

So how can they conclude that the results are "consistent with taking a legal dose"? The balance of probabilities also applies to weighing various other explanations. What is the probability he intentionally doped? What is the probability he intentionally inhaled too much, because he needed it, and lied about it? What is the probability that he accidentally inhaled too much, and didn't realize that? All of this was referred to by UCI when they stated as a factor in the decision that Froome was of course allowed to take some salbutamol for therapeutic purposes. It's not like EPO, where the probability that someone took it for doping would be considered very high.

I assume WADA decided all of these probabilities were less than 10% (or less than whatever the figure the model came up with), making the false positive, though quite unlikely, still the most likely scenario. The problem, of course, is there is no way to estimate accurately the probabilities of these other possibilities. It's sheer guesswork.

Medical science is not my forte, but common sense and logic tells me that if a rider like Froome, who must have been tested hundreds of times over the last 6 years, has never previously tested over the salbuatmol threshold, let alone record a result double the limit, despite supposedly taking the drug consistently for years, then the chances of his body producing such a result without him exceeding the maximum allowed dosage on that day must be infinitely small.

That's why it was so important for Froome to establish he didn't take 800 ug except on that one day, or a few other days. Part of the explanation for the spike is to be that he took far more that one day than he ordinarily did. The remainder of the argument is that there is very high variation in the relationship of dose take to urine level. However, the part about his exceeding the limit by so much is, as you allude to, harder to explain. If he went over the limit one time, one would expect it would not be by very much.

 

[Mamil]

Re: Re:

That's why it was so important for Froome to establish he didn't take 800 ug except on that one day, or a few other days. Part of the explanation for the spike is to be that he took far more that one day than he ordinarily did. The remainder of the argument is that there is very high variation in the relationship of dose take to urine level. However, the part about his exceeding the limit by so much is, as you allude to, harder to explain. If he went over the limit one time, one would expect it would not be by very much.

That makes sense. But as others have said, the fact that Froome has seemingly been allowed to use self-reporting of dosages as part of the reasoning for his results seems ludicrous, and a dangerous precedent, all the more so in the context of a threshold that is already acknowledged as generous, and a rider who at the time was winning a GT, rather than just clinging on and suffering in the grupetto. This is particularly so in the absence of any impartial, controlled baseline. Froome's team argued that a pharmacokinetic study was not relevant because it couldn't replicate GT conditions, but surely it should have been countered that it would still be important, indeed necessary, to obtain at least some idea of his dosage/concentration correlation in a controlled study, even if it couldn't be said that the results of this were definitive in determining whether the recorded result was possible. Otherwise Froome's results for each day are all based on unverified data, easily capable of manipulation.

But since the lawyers challenged the entire validity of the pharmacokinetic study as part of the AAF review model, since it can't replicate the exact conditions in which test results are obtained and was therefore probably argued as lacking procedural fairness for athletes, and WADA accepted this, then WADA's method for testing and making determinations on salbutamol AAFs, and any other controlled substances, is broken, whether they admit it or not. Once WADA accepted that their assessment model was defective, it's a quick and slippery slope to them caving in.

 

[gillan1969]

"When it was put to Wada that they only had Froome’s word for his salbutamol intake, Rabin accepted that he could not be “absolutely sure of the dose that has been taken”. He said: “That is not possible with the level of variability with salbutamol, for a simple reason – with inhaled salbutamol, part of it is going into your gut intestinal tract, very similar to an oral intake. So there is quite a bit of variability even for anyone inhaling.”"

https://www.theguardian.com/sport/2018/jul/13/chris-froome-wada-permitted-level-salbutamol-cut?CMP=share_btn_tw

Love the second part of his quote...nothing to do with the self reporting but hey...nothing like a red herring......

you can't make these guys up

 

[Merckx index]

"When it was put to Wada that they only had Froome’s word for his salbutamol intake, Rabin accepted that he could not be “absolutely sure of the dose that has been taken”. He said: “That is not possible with the level of variability with salbutamol, for a simple reason – with inhaled salbutamol, part of it is going into your gut intestinal tract, very similar to an oral intake. So there is quite a bit of variability even for anyone inhaling.”"

https://www.theguardian.com/sport/2018/jul/13/chris-froome-wada-permitted-level-salbutamol-cut?CMP=share_btn_tw

Love the second part of his quote...nothing to do with the self reporting but hey...nothing like a red herring......

you can't make these guys up

It's pretty simple logic. If you aren't allowed to believe Froome when he says he inhaled 800 ug, no more, on stage 18, then how can you believe him when he says how much he took on other stages? The whole point of the proceedings is because you can't take an athlete at his word. If they really wanted to know the relationship between dose and urine level, why didn't they have him do the lab tests? Even if they insist--without any published evidence, and in large part rejected by UCI--that the conditions in the Vuelta were different, wouldn't you want to do a lab test to show just how different the conditions were? Wouldn't that be pretty relevant to the next time a rider has an AAF in a GT?

The story also notes that the decision to allow Froome to skip the test was not made until near the end, in June. So either Froome took the test earlier, and failed, or he managed to stall all that time.

That bit about inhaling vs. swallowing is a red herring, but it could also be used against Froome's case. If their point is that more of it would be swallowed than inhaled during the race--because of the breathing hard, paying attention to the race, maybe the lung infection--then that should reduce urine levels, because swallowed salbutamol is metabolized and takes longer to be excreted. It might increase variability, but that's a factor that could easily be tested in the lab.

 

[chuuurles]

"When it was put to Wada that they only had Froome’s word for his salbutamol intake, Rabin accepted that he could not be “absolutely sure of the dose that has been taken”. He said: “That is not possible with the level of variability with salbutamol, for a simple reason – with inhaled salbutamol, part of it is going into your gut intestinal tract, very similar to an oral intake. So there is quite a bit of variability even for anyone inhaling.”"

https://www.theguardian.com/sport/2018/jul/13/chris-froome-wada-permitted-level-salbutamol-cut?CMP=share_btn_tw

Love the second part of his quote...nothing to do with the self reporting but hey...nothing like a red herring......

you can't make these guys up [/quote

It's pretty simple logic. If you aren't allowed to believe Froome when he says he inhaled 800 ug, no more, on stage 18, then how can you believe him when he says how much he took on other stages? The whole point of the proceedings is because you can't take an athlete at his word. If they really wanted to know the relationship between dose and urine level, why didn't they have him do the lab tests? Even if they insist--without any published evidence, and in large part rejected by UCI--that the conditions in the Vuelta were different, wouldn't you want to do a lab test to show just how different the conditions were? Wouldn't that be pretty relevant to the next time a rider has an AAF in a GT?

The story also notes that the decision to allow Froome to skip the test was not made until near the end, in June. So either Froome took the test earlier, and failed, or he managed to stall all that time.

Thank you for you're extremely insightful post's. I take their are no governing bodies to ever appeal this decision ?

 

[Robert5091]

https://www.theguardian.com/sport/2018/jul/13/chris-froome-wada-permitted-level-salbutamol-cut

Maybe the weakness in the system is that we are being too nice”...‘You are going to have to take less, otherwise you need a TUE.’”

Seems to be an admittance of a faulty testing system.

... in this particular case there was a procedural agreement made by the UCI with the athlete to give him an opportunity to provide his explanation in the early stage.

Niggli admitted that until last month Wada had nonetheless expected Froome to undergo the test. “However in June we received a lot of explanation and a lot of different studies from the athlete,” he said. “And there were two factors. One was that reproducing the same conditions from this athlete in this particular case was almost impossible, in particular because he had an illness.

“The second part is that we got explanations which experts came to the conclusion were not inconsistent with having taken a therapeutic dose.”

So did Cookson or Lappy agree to let Froome explain himself? Whoever did, was it a breach of protocol? The CPKT test is now useless since every case will say it can not reproduce conditions exactly. The whole procedure seems to be just dragging out a decision until Froome does the TdF. ASO threatening to not allow Froome to race seems to have quickened UCI's decision.

 

[wirral]

"When it was put to Wada that they only had Froome’s word for his salbutamol intake, Rabin accepted that he could not be “absolutely sure of the dose that has been taken”. He said: “That is not possible with the level of variability with salbutamol, for a simple reason – with inhaled salbutamol, part of it is going into your gut intestinal tract, very similar to an oral intake. So there is quite a bit of variability even for anyone inhaling.”"

https://www.theguardian.com/sport/2018/jul/13/chris-froome-wada-permitted-level-salbutamol-cut?CMP=share_btn_tw

Love the second part of his quote...nothing to do with the self reporting but hey...nothing like a red herring......

you can't make these guys up [/quote

It's pretty simple logic. If you aren't allowed to believe Froome when he says he inhaled 800 ug, no more, on stage 18, then how can you believe him when he says how much he took on other stages? The whole point of the proceedings is because you can't take an athlete at his word. If they really wanted to know the relationship between dose and urine level, why didn't they have him do the lab tests? Even if they insist--without any published evidence, and in large part rejected by UCI--that the conditions in the Vuelta were different, wouldn't you want to do a lab test to show just how different the conditions were? Wouldn't that be pretty relevant to the next time a rider has an AAF in a GT?

The story also notes that the decision to allow Froome to skip the test was not made until near the end, in June. So either Froome took the test earlier, and failed, or he managed to stall all that time.

Thank you for you're extremely insightful post's. I take their are no governing bodies to ever appeal this decision ?

If I understand correctly, this was a decision to discontinue proceedings, as opposed to any sort of ruling, by the UCI. The decision to discontinue proceedings was taken by the UCI after WADA withdrew scientific support for the case.

So, any "appeal" would be a resumption of proceedings, rather than an appeal. I think only WADA or the UCI could do that. The chances in reality are zero.

 

[Merckx index]

I’ve discussed the Froome case in detail elsewhere, and I think it will be online soon, but here’s another salient point. Glaxo’s Daren Austin claimed that in computer simulations, a false positive rate as high as 10% may have resulted. I assume by false positive, he means a sample exceeding 1200 ng/ml. But what would be the probability of exceeding Froome’s corrected value of 1430 ng/ml?

We can estimate an upper limit on that from some published data. Several studies have published mean +/- SD values for urinary concentrations in samples following inhalation of 800 ug. The highest SD reported was 285 ng/ml. Like all the published lab studies, this examined between-subject variation, giving a group of subjects the same dose of salbutamol, and taking samples a certain time later. Austin’s simulation was based on within-subject variation, taking samples at different times (every day in the Vuelta) from the same subject. It’s widely recognized that between-subject variation is usually greater than within-subject variation, because differences in physiology between different subjects are expected to be greater than fluctuations in physiology in a single subject. But to be conservative, let's assume that the variation in Froome’s samples was just as great, 285 ng/ml.

Using this value, and the 10% of samples exceeding 1200 ng/ml reported for Austin’s simulation, we can determine the % of samples exceeding 1430 ng/ml. The 10% figure corresponds to 1.3 SD above the mean in a random distribution, or 285 x 1.3 = 370 ng/ml. So the mean of Froome’s samples (as calculated for 800 ug inhalation) would be 1200 – 370 = 830 ng/ml. This is more than twice as high as the highest mean reported in lab studies, but it would be expected that if Austin’s simulations have any chance of reaching that 1430 ng/ml level, his mean value had to be much higher than the mean of other subjects. Outliers in the published studies have urinary levels around this high, and we assume Froome is an outlier.

If his mean value was 830 ng/ml, then 1430 ng/ml is 600 ng/ml above the mean, which = 2.1 SD (600/285). This corresponds to about 1.8% of samples. Thus if 10% of Froome’s samples were predicted to exceed the limit of 1200 ng/ml, less than 2% would exceed his actual value of 1430 ng/ml. In other words, the probability that Froome took more than 800 ug is > 98%. That sure sounds like beyond reasonable doubt territory to me. And remember, that is making very conservative assumptions that in effect increase the final probability of 1.8% calculated.

Now maybe Austin has very different numbers. Maybe he claims that Froome's samples, because of his efforts and illness, exhibited a degree of variation unknown to science previously. Maybe he claims that Froome's mean values are higher than just about any that have been published. Maybe he has reason to believe the distribution isn't random. But taking him at his word about a false positive rate of 10%; assuming Froome's typical urinary levels following inhalation of salbutamol are among the highest ever recorded; and assuming the variation among his samples is as high as the highest published between subject variation--that's being, to put it mildly, extremely generous. And unless/until the report is published, he and the rest of Froome’s defense, and WADA, and UCI, can count on more criticism like this.

 

[Merckx index]

Here’s a very interesting parallel to the Froome case. A few years after the EPO test was published and approved, a few cases of apparent false positives emerged. One involved Rutger Beke, a Belgian triathlete, who was originally sanctioned, but then won an appeal. Beke’ argument was that when he engaged in intense exercise, his body produced a lot of different proteins, one or more of which behaved like EPO on the gel test. He claimed that his kidneys malfunctioned, so that these proteins that normally would have been reabsorbed into the blood stream were excreted into the urine. Sound familiar?

After extensive lab tests, an article was published that upheld his claim:

http://www.bloodjournal.org/content/107/12/4711?ijkey=f4754747c0764b147009744d429d3883e5efed39&keytype2=tf_ipsecsha

Beke commented:

"EPO is a protein," Beke said. "Everybody has it in their body. The main problem is when I do high physical activity, especially anaerobic, I produce a lot of proteins. The problem is that with everybody else there is a filter in the kidneys that stops your proteins from ending up in your urine. When I do anaerobic exercise the filter doesn't work properly and all these proteins end up in my urine.

"Now the big problem is that the anti-doping agencies don't see that the EPO proteins I produce are the same as synthetic. So I had to prove that mine are natural. Unfortunately it took 10 months."

https://www.theguardian.com/sport/2005/sep/20/athletics.sport

The article, from 2005, concludes with this beauty: “it seems premature to condemn Armstrong and others as cheats.”

Suppose WADA had modified its rules, as it could have, to say that an EPO AAF would be cleared if the athlete could prove in the lab that he actually produced these proteins which interfered with the EPO test. Give Beke credit for doing that (though see below). Then suppose an athlete tested positive for EPO, but argued that because of illness and other factors, he could not replicate the conditions that led to secretion of these other proteins. WADA accepted this argument—citing unpublished studies that sometimes the conditions that resulted in an EPO false positive could not be replicated in the lab—and cleared the athlete.

This is basically the way the Froome case was handled. Notice that WADA did not simply break its own rule. There is nothing in the Code—wasn’t before, there isn’t now—that specifies that an athlete may be excused from the test if the conditions under which the AAF occurred can’t be replicated.

Oh, and there’s a relevant postscript to the case. Don Catlin examined Beke’s claims, and found several flaws in the study. And he concluded with this:

Finally, the athlete has a puzzling renal disease characterized by a concentrating defect and an excessive number of casts that apparently does not interfere with his athletic prowess. He should have a full nephrology evaluation.

http://www.bloodjournal.org/content/108/5/1778.1?sso-checked=true

I think Froome should have a full nephrology evaluation, too. After all, if he excretes salbutamol differently from everyone else while riding GTs, who knows what other havoc his kidneys may be wreaking on this body.

 

[Pantani_lives]

That's a very interesting explanation, Merckx index. I remember the case of Rutger Beke and I believe he was innocent and his case was well argued as a false positive. However in the case of Froome my guess is that his lawyers have studied precedents like this and used it to create "reasonable doubt" and let him get away with it.