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All About Salbutamol

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What will the verdict in Froome's salbutamol case?

He will be cleared
29
28%
3 month ban
3
3%
6 month ban
14
13%
9 month ban
23
22%
1 year ban
14
13%
2 year ban
19
18%
4 year ban
2
2%
 
Total votes : 104

Re: Re:

07 May 2018 22:12

Bolder wrote:However, this is probably the key takeaway, from Tucker: I think the point is that this is how Sky and Froome need it to be, and this study is a big bullet in their chamber. It’s all about sowing doubt.


It's not that simple. Sowing doubt won't help them and they know that. If the paper has anything to do with the case (and I think it does), they're gunning for that 15% possibility of a sample being a false positive.

I'm assuming this is all happening in preparation for the appeal. If that's the case, Froome's burden of proof will be on the balance of probabilities (s 3.1 of the UCI Anti-Doping Rules). He'll have to show that the sum total of his arguments tips the balance in his favor and that paper will be one of the arguments. How much weight the panel will give it, we don't know and neither do they but it's worth raising the argument in court. Marginal gains, every little bit helps.
User avatar fasthill
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08 May 2018 03:37

I had a chance to look at those five studies a little more closely, considering only the samples that were analyzed four hours (or earlier) after inhaling 800 ug. Only 3/168 subjects were > 1000, and only one, corrected for USG, was > 1200 ng/ml. Also, two of the studies reported samples at earlier times, including 30 minutes (8 samples, none > 1000); 1 hour (40 samples, none > 1000); and two hours (40 samples, one USG-corrected sample was > 1200). So 1/88 samples > 1000 and > 1200.

Heuberger et al. say their model predicts 15% of samples > 1000 at one hour, and 3% > 1000 at four hours. The only empirical evidence they cite is one study in which 1/28 samples was > 1000, close to their 3% prediction. But in the much larger sample size* of five studies I looked at—which includes the one Heuberger et al referred to plus four others—less than 2% of the samples were > 1000, and about half of the samples in this pool were taken at two hours or sooner, which should have increased the proportion > 1000. Particularly damning are the 48 samples taken at one hour or earlier. If the predicted proportion > 1000 is 15%, it’s highly improbable that 0/48 by chance would be > 1000.

*The effective sample size is even larger than I've indicated, because for many samples, two values are reported--uncorrected and corrected for USG. I count these two values as corresponding to one sample.

Elers1: http://sci-hub.tw/10.1249/MSS.0b013e3181b2e87d
Elers2: http://sci-hub.tw/10.1097/JSM.0b013e31823513e1
Mareck: http://sci-hub.tw/10.1002/dta.367
Dickinson: http://sci-hub.tw/10.1097/jsm.0000000000000072
Sporer: http://sci-hub.tw/10.1097/JSM.0b013e3181705c8c

Everyone has pointed out that this is just a theoretical model, but there’s another very important point that’s generally missed. Their case is based on the conclusion that the concentration of salbutamol in the urine reaches a peak very fast—within thirty minutes to an hour. They don’t say this, or at least emphasize it, but most of the empirical salbutamol studies are based on longer times before the urine sample is taken—four hours or more.

This is critical, because it allows them to make this claim of 15% over the threshold without an apparent contradiction with the empirical data. They’re implying the reason most studies don’t show many samples > 1000 is because they don’t take the samples early enough. But as I’ve just shown, there are enough data at these earlier times to call into serious question this premise.

These other studies do support Heuberger’s conclusion that urine level of salbutamol peaks at about one hour after inhalation, but it doesn’t appear to drop dramatically between then and four hours. The Sporer paper reports that the mean urine concentration at 2 hours is 70-80% that at one hour, a difference that is not significant.

A generally similar decrease of mean values was found from 1.5 to 4 hr in the Haase study, which was the one supplying some of the data Heuberger et al used to construct their model. Haase et al tested inhalation of 1600 ug only. In that study, more samples > 1000 were generally found at 1.5 hr than 4 hr, but the difference was not that great. Across all three conditions, and including corrected and uncorrected values, there was a total of 28 samples > 1000 at 1.5 hr vs. 23 at 4 hr. Using the 1200 ng/ml DL, it was 21 vs. 18. This is not consistent with Heuberger et al's prediction that the proportion of samples > 1000 after 1 hr is five times that at four hr. (N.B.: The Haase values are take from Table 2 of their paper; the same values are nominally included in Fig. 2, but several of them are wrong, as easily can be seen by counting the number of points above the threshold line; I don't know how this got past the reviewers).

Haase: http://sci-hub.tw/10.1002/dta.1828
Merckx index
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Re: All About Salbutamol

08 May 2018 08:47

I am presuming that the strategy is, that knowing they will never replicate the levels, they are going down Froome's 'point of view' approach. For the fans the headlines will be enough...exactly the same as 'he just lost the fat'...use the media and the academics (or 'usefool fools') to create the narrative.....

Sky can claim that there is enough doubt to maintain the charade that they are clean, they don't need to fire Froome and Froome can continue to express innocence whilst having to take a short ban on the chin....
gillan1969
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Re: All About Salbutamol

08 May 2018 10:23

gillan1969 wrote:I am presuming that the strategy is, that knowing they will never replicate the levels, they are going down Froome's 'point of view' approach. For the fans the headlines will be enough...exactly the same as 'he just lost the fat'...use the media and the academics (or 'usefool fools') to create the narrative.....

Sky can claim that there is enough doubt to maintain the charade that they are clean, they don't need to fire Froome and Froome can continue to express innocence whilst having to take a short ban on the chin....


That's the second line of defence, assuming Froome is banned, trying to keep the fanboys onside, just a PR exercise really

The first line of defence, the legal battle, is Mike Morgan opening multiple fronts on the AAF in the hope that something sticks. So as well a legal/procedural arguments (chain of custody, etc) Morgan also has medical/scientific arguments (kidney malfunction/antibiotics and, on a more fundamental level, trying to undermine the test itself - an approach that worked in Morgan's defence of footballer Mamadou Sahko)

Morgan has no idea if the LADS/ADT will latch onto any of these multiple fronts or whether cumulatively they might sway the judge. The fact that Froome's defence is so exhaustive suggests that Morgan doesn't have an obvious knockout blow. That doesn't mean Morgan isn't going to get the Dawg a free pass, btw. All contentious legal matters have a high degree of uncertainty built in

Incidentally, it's always worth bearing in mind that this matter could have been resolved very quickly if only our hero was able to go into a lab, take a legal dose of salbutamol and repeat the AAF level that tripped the wire
Wiggo's Package
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Re: All About Salbutamol

08 May 2018 14:44

Wiggo's Package wrote:
gillan1969 wrote:I am presuming that the strategy is, that knowing they will never replicate the levels, they are going down Froome's 'point of view' approach. For the fans the headlines will be enough...exactly the same as 'he just lost the fat'...use the media and the academics (or 'usefool fools') to create the narrative.....

Sky can claim that there is enough doubt to maintain the charade that they are clean, they don't need to fire Froome and Froome can continue to express innocence whilst having to take a short ban on the chin....


That's the second line of defence, assuming Froome is banned, trying to keep the fanboys onside, just a PR exercise really




The first line of defence, the legal battle, is Mike Morgan opening multiple fronts on the AAF in the hope that something sticks. So as well a legal/procedural arguments (chain of custody, etc) Morgan also has medical/scientific arguments (kidney malfunction/antibiotics and, on a more fundamental level, trying to undermine the test itself - an approach that worked in Morgan's defence of footballer Mamadou Sahko)

Morgan has no idea if the LADS/ADT will latch onto any of these multiple fronts or whether cumulatively they might sway the judge. The fact that Froome's defence is so exhaustive suggests that Morgan doesn't have an obvious knockout blow. That doesn't mean Morgan isn't going to get the Dawg a free pass, btw. All contentious legal matters have a high degree of uncertainty built in

Incidentally, it's always worth bearing in mind that this matter could have been resolved very quickly if only our hero was able to go into a lab, take a legal dose of salbutamol and repeat the AAF level that tripped the wire


I think if LADS have referred this on to the next stage, they a) were confident of their case and b) most likely took legal advice themselves from a higher source (trust me from a previous life this happens more than you might think).
User avatar ferryman
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Re: All About Salbutamol

08 May 2018 15:40

ferryman wrote:
Wiggo's Package wrote:
gillan1969 wrote:I am presuming that the strategy is, that knowing they will never replicate the levels, they are going down Froome's 'point of view' approach. For the fans the headlines will be enough...exactly the same as 'he just lost the fat'...use the media and the academics (or 'usefool fools') to create the narrative.....

Sky can claim that there is enough doubt to maintain the charade that they are clean, they don't need to fire Froome and Froome can continue to express innocence whilst having to take a short ban on the chin....


That's the second line of defence, assuming Froome is banned, trying to keep the fanboys onside, just a PR exercise really




The first line of defence, the legal battle, is Mike Morgan opening multiple fronts on the AAF in the hope that something sticks. So as well a legal/procedural arguments (chain of custody, etc) Morgan also has medical/scientific arguments (kidney malfunction/antibiotics and, on a more fundamental level, trying to undermine the test itself - an approach that worked in Morgan's defence of footballer Mamadou Sahko)

Morgan has no idea if the LADS/ADT will latch onto any of these multiple fronts or whether cumulatively they might sway the judge. The fact that Froome's defence is so exhaustive suggests that Morgan doesn't have an obvious knockout blow. That doesn't mean Morgan isn't going to get the Dawg a free pass, btw. All contentious legal matters have a high degree of uncertainty built in

Incidentally, it's always worth bearing in mind that this matter could have been resolved very quickly if only our hero was able to go into a lab, take a legal dose of salbutamol and repeat the AAF level that tripped the wire


I think if LADS have referred this on to the next stage, they a) were confident of their case and b) most likely took legal advice themselves from a higher source (trust me from a previous life this happens more than you might think).


I can imagine there's all kinds of back traffic on a case like this!

Btw, what do you mean by "higher source"?

Counsel's opinion? One of the ADT judges? (But not the one chosen I would hope)
Wiggo's Package
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Re: All About Salbutamol

08 May 2018 16:06

Wiggo's Package wrote:
ferryman wrote:
Wiggo's Package wrote:
gillan1969 wrote:I am presuming that the strategy is, that knowing they will never replicate the levels, they are going down Froome's 'point of view' approach. For the fans the headlines will be enough...exactly the same as 'he just lost the fat'...use the media and the academics (or 'usefool fools') to create the narrative.....

Sky can claim that there is enough doubt to maintain the charade that they are clean, they don't need to fire Froome and Froome can continue to express innocence whilst having to take a short ban on the chin....


That's the second line of defence, assuming Froome is banned, trying to keep the fanboys onside, just a PR exercise really




The first line of defence, the legal battle, is Mike Morgan opening multiple fronts on the AAF in the hope that something sticks. So as well a legal/procedural arguments (chain of custody, etc) Morgan also has medical/scientific arguments (kidney malfunction/antibiotics and, on a more fundamental level, trying to undermine the test itself - an approach that worked in Morgan's defence of footballer Mamadou Sahko)

Morgan has no idea if the LADS/ADT will latch onto any of these multiple fronts or whether cumulatively they might sway the judge. The fact that Froome's defence is so exhaustive suggests that Morgan doesn't have an obvious knockout blow. That doesn't mean Morgan isn't going to get the Dawg a free pass, btw. All contentious legal matters have a high degree of uncertainty built in

Incidentally, it's always worth bearing in mind that this matter could have been resolved very quickly if only our hero was able to go into a lab, take a legal dose of salbutamol and repeat the AAF level that tripped the wire


I think if LADS have referred this on to the next stage, they a) were confident of their case and b) most likely took legal advice themselves from a higher source (trust me from a previous life this happens more than you might think).


I can imagine there's all kinds of back traffic on a case like this!

Btw, what do you mean by "higher source"?

Counsel's opinion? One of the ADT judges? (But not the one chosen I would hope)


A lawyer is a lawyer (solicitor in Scotland), but yes we would take QC advice on particularly complex situations. It's not as expensive as you may think and not always in your favour (despite how you may put your case to them!!)
User avatar ferryman
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Re: All About Salbutamol

08 May 2018 20:23

ferryman wrote:
Wiggo's Package wrote:
ferryman wrote:
Wiggo's Package wrote:
gillan1969 wrote:I am presuming that the strategy is, that knowing they will never replicate the levels, they are going down Froome's 'point of view' approach. For the fans the headlines will be enough...exactly the same as 'he just lost the fat'...use the media and the academics (or 'usefool fools') to create the narrative.....

Sky can claim that there is enough doubt to maintain the charade that they are clean, they don't need to fire Froome and Froome can continue to express innocence whilst having to take a short ban on the chin....


That's the second line of defence, assuming Froome is banned, trying to keep the fanboys onside, just a PR exercise really




The first line of defence, the legal battle, is Mike Morgan opening multiple fronts on the AAF in the hope that something sticks. So as well a legal/procedural arguments (chain of custody, etc) Morgan also has medical/scientific arguments (kidney malfunction/antibiotics and, on a more fundamental level, trying to undermine the test itself - an approach that worked in Morgan's defence of footballer Mamadou Sahko)

Morgan has no idea if the LADS/ADT will latch onto any of these multiple fronts or whether cumulatively they might sway the judge. The fact that Froome's defence is so exhaustive suggests that Morgan doesn't have an obvious knockout blow. That doesn't mean Morgan isn't going to get the Dawg a free pass, btw. All contentious legal matters have a high degree of uncertainty built in

Incidentally, it's always worth bearing in mind that this matter could have been resolved very quickly if only our hero was able to go into a lab, take a legal dose of salbutamol and repeat the AAF level that tripped the wire


I think if LADS have referred this on to the next stage, they a) were confident of their case and b) most likely took legal advice themselves from a higher source (trust me from a previous life this happens more than you might think).


I can imagine there's all kinds of back traffic on a case like this!

Btw, what do you mean by "higher source"?

Counsel's opinion? One of the ADT judges? (But not the one chosen I would hope)


A lawyer is a lawyer (solicitor in Scotland), but yes we would take QC advice on particularly complex situations. It's not as expensive as you may think and not always in your favour (despite how you may put your case to them!!)


Thanks, understood

IME you'd need a QC well versed in sports doping litigation to make the exercise worthwhile. And with Froome having spent $1m+ on legal fees the binders would be daunting!

Again IME counsel's opinions almost always favoured the side paying for it (a cynic might suggest the QC has an eye on more work down the line!). And usually came with many qualifiers (more understandable given how unpredictable litigation can be)

Slight digression but in Froome's case there have been suggestions (can't recall the source now) that LADS were referring elements of the case to the ADT while LADS still had jurisdiction. That seems odd if true but of course we don't know the context or the details
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11 May 2018 03:45

There are some real empirical problems for Heuberger et al. Sporer et al. studied 37 subjects—the largest pool in any salbutamol study testing the WADA limits that I’m aware of—took urine samples after 1 hour, and none was > 1000, not even close (highest was 831). The same group also performed another study of 8 subjects, taking samples at 30m and 1 hr, and again, no samples > 1000. That’s 53 samples with none > 1000, whereas Heuberger’s model predicts there should be eight. The probability of getting none in a pool that size would be about one in five thousand.

http://sci-hub.tw/10.1097/JSM.0b013e3181705c8c
https://sci-hub.tw/10.1249/mss.0b013e3181591df7

There’s also a total of 187 samples from seven studies, including the two Sporer ones, in which urine samples were taken at 4 hr or sooner, and only 3 were > 1000. That would be roughly consistent with the 3% Heuberger et al predict for four hours, except that almost 30% of these are the aforementioned 1 hr samples, and another 20+% of these samples were taken after two hours. Though Heuberger doesn’t report what the model predicts for that time, it would probably be in the range of 5-10%. So one would predict more than a dozen samples in this pool should be > 1000.

The biggest problem with Heuberger’s study is that they don’t provide essential information. They say that the 15.4% value is shown in Fig. 3, but it isn’t. All Fig. 3 shows is the predicted mean value of salbutamol concentration, and the 99.9% limits. This information, alone, is not enough to allow one to tell what % of samples will be > 1000, 1200, or any other arbitrary level. My guess from what Fig. 3 does show is that the predicted one hour values are very sensitive to small changes in conditions or parameters, and that they have overestimated the difference between 1 hr and 4 hr levels. In fact, the mean values at those times are virtually identical.

I assume that when the paper is actually published, the details will be provided in an Appendix. While they’re at it, they should also correct the glaring error in the first paragraph, in which they state that the 800 ug dose is the maximum allowed with a TUE, and that Froome had a TUE. I guess not being aware that no TUE has been required for salbutamol up to that level for several years is at least evidence that they aren’t too close to Froome and his team.
Merckx index
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Re:

11 May 2018 09:23

Merckx index wrote:I guess not being aware that no TUE has been required for salbutamol up to that level for several years is at least evidence that they aren’t too close to Froome and his team.
The notes of the paper said one author is a hobby cyclist and the other is a fan who watches cycling on TV. These are the same people who produced the "EPO doesn't work" study.

They seem like the academic equivalent of Anthony Tan, attention-seekers who write willfully-oblivious troll articles in order to be provocative. There is always a good role for contrarians, however - having to respond to them strengthens the body of knowledge about the subjects
ClassicomanoLuigi
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Re: All About Salbutamol

11 May 2018 10:34

Froome is asked to do a PK test and replicate his alleged dosage which was 5 divided puffs
Then when that figure gets adjusted for SG ...
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Re:

13 May 2018 00:28

Merckx index wrote:There are some real empirical problems for Heuberger et al. Sporer et al. studied 37 subjects—the largest pool in any salbutamol study testing the WADA limits that I’m aware of—took urine samples after 1 hour, and none was > 1000, not even close (highest was 831). The same group also performed another study of 8 subjects, taking samples at 30m and 1 hr, and again, no samples > 1000. That’s 53 samples with none > 1000, whereas Heuberger’s model predicts there should be eight. The probability of getting none in a pool that size would be about one in five thousand.

http://sci-hub.tw/10.1097/JSM.0b013e3181705c8c
https://sci-hub.tw/10.1249/mss.0b013e3181591df7

There’s also a total of 187 samples from seven studies, including the two Sporer ones, in which urine samples were taken at 4 hr or sooner, and only 3 were > 1000. That would be roughly consistent with the 3% Heuberger et al predict for four hours, except that almost 30% of these are the aforementioned 1 hr samples, and another 20+% of these samples were taken after two hours. Though Heuberger doesn’t report what the model predicts for that time, it would probably be in the range of 5-10%. So one would predict more than a dozen samples in this pool should be > 1000.

The biggest problem with Heuberger’s study is that they don’t provide essential information. They say that the 15.4% value is shown in Fig. 3, but it isn’t. All Fig. 3 shows is the predicted mean value of salbutamol concentration, and the 99.9% limits. This information, alone, is not enough to allow one to tell what % of samples will be > 1000, 1200, or any other arbitrary level. My guess from what Fig. 3 does show is that the predicted one hour values are very sensitive to small changes in conditions or parameters, and that they have overestimated the difference between 1 hr and 4 hr levels. In fact, the mean values at those times are virtually identical.

I assume that when the paper is actually published, the details will be provided in an Appendix. While they’re at it, they should also correct the glaring error in the first paragraph, in which they state that the 800 ug dose is the maximum allowed with a TUE, and that Froome had a TUE. I guess not being aware that no TUE has been required for salbutamol up to that level for several years is at least evidence that they aren’t too close to Froome and his team.


I belive in MI.

Doubt him at your peril.
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Re: All About Salbutamol

15 May 2018 23:42

Getting close to my usual summer asthma season and still breathing freely. Went for a group run today, 12-13kph, 98kg dry. Untrained other than relatively tame bike communiting.

What do you asthma wussies do to aleviate symptoms without going for the lazy drugger's first choice?
Cloxxki
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