[search]

I really struggle a bit to get excited tbh, although the Giro is my favorite stage race. But on the other hand: the way Sky is usually racing there, he's going to DNF early on anyway. So it shouldn't make much of a difference.

[AG]

as much as I think Chris Froome is guilty - and has dealt with this situation terribly (as has the UCI) ... it isnt that different from any other rider starting.

We know they take drugs, we know they are dirty as hell.  Valverde, Nibali, Froome, Contador, Quintana ... you cant name a GT winner in recent (or longer) times that was clean.

I hope he doesnt win as it is a terrible look for cycling, but I will still watch.

[Capt_Cavman]

It would be a bit like 2011 in where I found myself cheering on the decidedly dodgy Scarponi in his battle with the decidedly dodgy Nibali in their battle for 2nd place for no rational reason, in the expectation that the winner on the road would be stripped of his title.

Unsatisfactory yes, but that's cycling.

[pastronef]

https://www.sciencedaily.com/releases/2018/05/180503142737.htm

Study points to the futility of urine tests for salbutamol doping 

[t-72]

https://www.sciencedaily.com/releases/2018/05/180503142737.htm

Study points to the futility of urine tests for salbutamol doping 

Publication date May 3rd, 2018 - that's hardly a coincidence, is it?

[search]

here is another study by Mr Heuberger:

https://www.researchgate.net/publication/233874522_Erythropoietin_doping_in_cycling_Lack_of_evidence_for_efficacy_and_a_negative_risk-benefit

so... well.

Geert Leinders has also studied at exactly that University of Leiden by the way

[Capt_Cavman]

Robert Mugabe studied at Oxford. Is there a closer connection?

[search]

no idea. I mean, this is pretty obviously commissioned by Team Sky - but it could very well be a coincidence of course. They don't necessarily need to know each other, even if they are from the same city.

[Joelsim]

no idea. I mean, this is pretty obviously commissioned by Team Sky - but it could very well be a coincidence of course. They don't necessarily need to know each other, even if they are from the same city.

If it had been commissioned by Team Sky then it’s unlikely it’d have been published

Probably.

;-)

[search]

what makes you think so? Or, who else would pay for a study with the "aim to determine whether current approaches are sufficiently able to differentiate approved usage from violations"?

They clearly refer to the matter of "inhalation of salbutamol [...] restricted by the World Anti-Doping Agency (WADA)" and the reasons that"[r]ecently one of the most successful male cyclists of the last decade, Chris Froome, came into disrepute due to news of a potential doping violation".

I can't really see this being funded by a state university.

[Mellow Velo]

 I dunno what to think.
The journal seems to be a monthly publication for this lot.

https://en.wikipedia.org/wiki/British_Pharmacological_Society

They must be kosher, so I suppose it's down to whoever edits the content.
Brown envelope?
I agree with Search, given the WADA connection, Froome is the heavy favourite.
Loughborough would be the only uni that might fund something like this.

[Caruut]

The authors declare no conflicts of interest. JH is a recreational cyclist and is a fan of professional road cycling, but other than as a spectator and from its clinical pharmacology aspects not involved in the sport. SvD and AC watch professional cycling but are mainly excited by its clinical pharmacology aspects.

No declared conflict of interests. A few points come to mind.

1. This is a bona fide thing for these scientists to be looking at, and if they ahve a research budget, which some scientists do, they can choose to look at it.

2. The brown envelope could have been something "in-kind" if the researchers were cycling fans - possibly a meeting with a very grateful Chris Froome?

3. Universities are often very keen to do research that they think can generate press; this is bound to. Perhaps the researcher (or their superiors) just jumped at the chance to maybe get in the paper. Funders also like things that are "topical", which this is.

4. Team Sky and British Cycling have a pretty generous research budget, and close relationship with some scientists. They certainly have the contacts to put out that they want this research done, and maybe hint that some of that research budget might find itself flowing to Leiden, for example.

5. Maybe they are just blinkered superfans who desperately want to believe what they see on the road. To me that EPO paper jumps out as a huge red flag, either of someone deluding themselves or being paid to delude others.

So I think it's very possible that the research was produced without commission, or with only an implicit one.

The  WADA prohibited  list  indicates  that  salbutamol  use  is  allowed  in  inhaled  dosages  up  to “1600 micrograms  over  24 hours  in  divided  doses  not  to  exceed  800  micrograms  over  12  hours starting from any dose”, whichis considered the maximum therapeutic dose for athletes with a so-called Therapeutic Use Exemption (TUE). Froome was in possession of such a TUE, but “the presence in urine of salbutamol in excess of 1000 ng/mL [...] is presumed not to be an intended  therapeutic  use  of  the  substance  and  will  be  considered  as  an  Adverse  Analytical Finding  unless the athlete  proves,  through  a  controlled  pharmacokinetic  study,  that  the abnormal result was the consequence of the use of the therapeutic dose (by inhalation) up to the maximum dose indicated above.”

This much we knew, but bear with me...

Finally, our  model  is supported by data  from  a clinical  study [30],reporting that  out  of  28 subjects  (including  8  asthmatic  elite  athletes)  inhaling  a  single  dose  of  800  mcg  of salbutamol, there was one subject with a urine concentration above the 1000 ng/mL threshold when  analysing  the  urine  sample  taken  4  hours  post-dose.

So, essentially, they have built a model of how they think salbutamol will behave. This is then considered supported on the basis of a single person who tested positive under these conditions. EDIT: to be clear, their model predicted one person testing positive, so yes the results line up but they seem weak. I also don't know how reliable pharmokinetic modelling is. I do some economic modelling, which probably gives me an excessively negative view about the reliability of models...

Without such dense data, uncertainty in estimating the dose would result due to individual pharmacokinetic variability and  the  unknown factor  of  time since  dosing. Seen  how the  performance  enhancing  activity of beta-2 agonists is dubious, especially in endurance sports, the question arises whether it is worth the effort of screening for these compounds.

To my reading, the paper's effective conclusion is that, absent near-constant testing, salbutamol abuse cannot be conclusively proved without setting an unreasonable burden on the rider, so should be tolerated because they don't believe it to have any effect.

The authors seem basically unwilling to accept any form of strict liability placed upon the rider.

[Caruut]

I dunno what to think.
The journal seems to be a monthly publication for this lot.

https://en.wikipedia.org/wiki/British_Pharmacological_Society

They must be kosher, so I suppose it's down to whoever edits the content.
Brown envelope?
I agree with Search, given the WADA connection, Froome is the heavy favourite.
Loughborough would be the only uni that might fund something like this.

I was curious about this - the editor-in-chief is Adam F Cohen, co-author of the paper, former director of CHDR Leiden, where Heuberger is based, and the current director of CHDR's commercial consultancy arm InnoS (https://chdr.nl/clinical-studies-development/chdr-innos).

I wouldn't say this is dodgy per se, plenty of scientific subfields are small enough that there are only about 3 research units and 1 journal in the specific subfield, so there's bound to be a lot of crossover.

But... one has to imagine that articles where the lead author is a junior of the EiC and the EiC himself is a coauthor have a slightly easier time getting themselves published.

[search]

well, if this theoretical model (based on a study with dogs) really is a "key plank" of Froome's defense, there's not much hope left for him I guess.

Chris Froome’s fight to clear his name is set to become a high-stakes battle with the World Anti-Doping Agency after a new study claimed that the test for asthma medication is “fundamentally flawed”.

The research paper, published last week in the British Journal of Clinical Pharmacology, is understood to highlight a key plank of Froome’s defence – that Wada’s test for salbutamol is unreliable and needs to be overhauled.

https://www.thetimes.co.uk/article/study-raises-doubts-about-chris-froomes-salbutamol-test-ldbsx5sdn

[LukasCPH]

essentially, they have built a model of how they think salbutamol will behave. This is then considered supported on the basis of a single person who tested positive under these conditions.

So out of 28 people, one tested positive despite taking no more than the allowed dose = false positive.
Yeah, we already knew that there is a possibility of false positives. That's why there is a provision in the rulebook that an athlete found to exceed the allowed salbutamol level in their urine sample can try to prove their innocence through a controlled pharmacokinetic study which shows that this would indeed be the case for them.

This study, whoever funded it, tells us nothing new, as I see it, and is of little if any help to Froome in his fight for acquittal.
Nobody serious ever doubted that false positives were possible. But it's on Froome to prove that his positive was a false positive.

[AG]

Its not a study.  Its a theoretical drawing of conclusions from 3 or 4 existing studies ...

so no, it doesnt tell us anything new.

[Merckx Index]

I've critiqued this paper extensively at CN's Clinic. Just a few summary points:

1) The model is not supported by available empirical data. The authors cite one study in which 1/28 samples was > 1000, in rough agreement with their predicted 3% rate for samples taken after 4 hr. But an examination of 7 studies in which samples were taken 4 hr or sooner finds a total of only 3/187 samples > 1000, and about half of the samples were taken at 2 hr or earlier, which should have increased the proportion above threshold in the range of 5-10%. Their model would thus predict roughly about 14 samples > 1000 in this pool of 187 samples. Even worse, two papers in that group of seven report a total of 53 samples taken 1 hour after inhalation, with none > 1000. The model predicts 8, and the odds of finding none  by chance, given the 15% figure predicted by the model, are about 1 in 5000.

2) Even if the model were actually more or less correct, Froome would need to establish that he took 800 ug within an hour or so of providing the sample. And even then the odds of getting his corrected value of 1429 ug/ml would be < 10%. So in the best case scenario, the odds that the model won't explain his level are > 90%. Keep in mind that the standard of proof for doping cases is between preponderance of evidence and beyond reasonable doubt, so this falls well within that range.

3) The authors have not provided any details that allow one actually to evaluate their model. The data they show don't indicate 15.4% of samples taken at one hour would be > 1000 ng/ml. These data are presumably in an Appendix that will be made available upon publication, but it strikes me as a little unfair to announce a conclusion without actually showing the data that support it. This is particularly a problem here, because without these data we don't know exactly what the model predicts for the odds of Froome's level. We know they're < 10%, because that's the probability for a value > 1200, but that's all they say. They also give a figure of 3% for samples taken at 4 hr, but again, that's only for 1000 ng/ml, not Froome's level.

[AG]

http://www.cyclingnews.com/news/anti-doping-delay-leaves-chris-froome-missing-helicopter-transfer-giro-ditalia-shorts/#disqus_thread

the interesting part of this story is that he took a nature break with 30km to go.  On Mt Etna ... so essentially while they were already climbing.    WTF ???


And even so - 30km to go uphill means at least another hr ... then 2 hrs more to provide a sample ... so he needed 3 hrs to make enough pee for a sample?    really?   


but we need to give him the benefit of the doubt of course 

[Mellow Velo]

http://www.cyclingnews.com/news/anti-doping-delay-leaves-chris-froome-missing-helicopter-transfer-giro-ditalia-shorts/#disqus_thread

the interesting part of this story is that he took a nature break with 30km to go.  On Mt Etna ... so essentially while they were already climbing.    WTF ???


And even so - 30km to go uphill means at least another hr ... then 2 hrs more to provide a sample ... so he needed 3 hrs to make enough pee for a sample?    really?   


but we need to give him the benefit of the doubt of course 

 I'm a bit mystified as to what you think he's done wrong here and as to why a rider can't "dry up" in the last 20kms or so of a hard climb.
From my experience, not being able to give a sample after competition occurs quite a lot.

[AG]

well I guess its my own experiences coming to the fore here then

I have never, ever, ever needed 3 hrs to pee.  Ever.

[Merckx Index]

http://www.cyclingnews.com/news/anti-doping-delay-leaves-chris-froome-missing-helicopter-transfer-giro-ditalia-shorts/#disqus_thread

so he needed 3 hrs to make enough pee for a sample?    really? 

Not three hours. The problem is that he peed shortly after reaching the finish, in the doping control, but not enough. The minimum required I think is 90 ml. If you don't reach that volume, the sample is thrown out and you have to start over. And that leads to the next point...

 

I'm a bit mystified as to what you think he's done wrong here and as to why a rider can't "dry up" in the last 20kms or so of a hard climb.
From my experience, not being able to give a sample after competition occurs quite a lot.

Maybe Froome really had to go and couldn't wait, agreed, BUT...It's interesting in that peeing shortly before the finish of a race is just what you would do if you wanted to minimize the chances of testing over the threshold for a drug like salbutamol. First, you remove a lot of the salbutamol from your system by peeing near the end of the race. Then, because of that earlier urination, you don't produce enough urine for the required sample, so you remove still more salbutamol from your system--that urine sample is discarded. By the time Froome finally produced the required volume of urine, the level of salbutamol would have been considerably lower than it would have been had he waited till the end of the stage and given a urine sample that would have been of the required volume. Much of any salbutamol that he inhaled before that final 30 km would have been flushed out of his system when he stopped during the race, and if he inhaled later during that final 30 km, much of that would have been flushed out in the discarded urine sample initially given at doping control.

Heuberger et al,, in that theoretical article we've just been discussing, pointed this out as a problem with the doping control. Because urine levels of salbutamol are maximal within an hour of inhaling, urinating shortly before testing, and/or not being able to produce the required amount during testing, is a simple way to reduce the tested level.

I'm not accusing Froome of doing this intentionally to avoid a possible second positive, but it's certainly worth pointing out that this behavior is what he would do if he were at all concerned about being over the threshold again.

[Mellow Velo]

well I guess its my own experiences coming to the fore here then

I have never, ever, ever needed 3 hrs to pee.  Ever.

What woman has!

[Drummer Boy]

This has been making the rounds, and certainly deserves a place in this thread.


https://twitter.com/cyclingpro/status/996012369993224192

[rote_laterne]

He doesn't perform therefore he isn't suffering from performance induced asthma and doesn't need salbutamol at the moment. All pretty clear.

[Drummer Boy]

https://twitter.com/ammattipyoraily/status/997870647035531270

[L'arri]

Breathtaking ride from Froome today. Third week just got busy.

[Drummer Boy]

Breathtaking ride from Froome today.

Breathtaking for everyone except Froome, maybe.

[Joelsim]

Breathtaking for everyone except Froome, maybe.

Froome and Yates put an awful lot into that today. I think there are still some swings and roundabouts to come in this race.

[Mellow Velo]

https://twitter.com/ammattipyoraily/status/997870647035531270

Wow, 6th fastest, beaten by the Little Prince.
And no mention that Dumoulin's time was seven seconds faster than Basso, when he won the stage in 2010?
Statistics? I just enjoyed a great bike race today.

[Carlo Algatrensig]

Wow, 6th fastest, beaten by the Little Prince.
And no mention that Dumoulin's time was seven seconds faster than Basso, when he won the stage in 2010?
Statistics? I just enjoyed a great bike race today.

I only saw the highlight today on quest where they just showed the last 10km. It was a good race and although I knew the result when I watched it I was still thinking Yates could bridge the gap to Froome and win the stage.