Pulling a Wiggins

[Eyeballs Out]

I had a quick look. There are a fair few problems but the biggest is that there is no baseline data for the groups. Without it it's impossible to draw the conclusions they have done.

Why you do not like those conclusions? You say there are no baselines but their approach is not comparing measurements against the baselines. It is important to realise that CNAC and NAC are the same people. They took 15 people and did the first test during 8 days. Then they allowed for "wash-out" 3-week period and did the second test. They do not mention whether the first test was with NAC and the second with placebo, or vice versa, but let's assume results are not affected by the sequence.

So what they actually measured was that the same people had different blood values after taking NAC than they had after taking placebo. Isn't it then a fair conclusion that NAC had some effect on the blood? The measurements they did after trial with placebo can in fact be considered as the baseline you were missing, no?

No, they can't, for several reasons:

1) You cannot use the same participants for case and control in a double blind study, it's impossible and means that either it was singly blind, open or they don't actually know what they were doing.

2) They do not specifically state the order but they state the wash out period occurred between thiol and placebo treatment. This implies that the thiol treatment happened first and as such they have no baseline data.

3) They have no baseline data for the control/placebo study and you can't just assume it has no effect, you actually have to show that. Again, this means they have no baseline data for their NAC experiment.

These three things alone completely invalidate the conclusions. There is also the small size of the groups to take into account.

The numbers they report seem strange too, although this isn't my area. They show a higher hematocrit and EPO but lower RBC counts which doesn't make sense based on my understanding. The MCV has increased which is what has increased the hematocrit, but at they haven't assessed the Hb-O2 we have not idea if that would even have an effect on exercise (not the point of the study but it is the conclusion people are drawing). They don't address the change in MCV in the discussion. If these are the same people that would be something that really needs addressing.

They haven't assessed the exercise performance so I don't really understand the point of including it, maybe I'm missing it?

Honestly, it reads like a final year project that was written up as a paper. This isn't a problem, the problem is people taking the results and drawing conclusions that really can't be drawn. This is compounded when a respected scientist highlights the work as people who don't really understand it will assume it's right.

It was a crossover design wasn't it ? (or two crossovers). What you wrote in 1) and 2) doesn't apply unless I misunderstand. Agree it would be nice to see baseline results for start of each period just to confirm randomization and sufficient washout but I don't see that as reason to dismiss the results necessarily

 

[Irondan]

Re: Re:

That's probably fair enough.

And props for checking it instead of just accepting it.

What is interesting is that fumacil is not recommended for asthma patients.
And the fact that Matt Lawton is tweeting about this seems to suggest he knows what was really in the bag and that it wasn't fumacil.

I wonder what legal obstacles there might be for Matt that might prevent him from publishing what was in the bag according to his informant.

Here is the problem manifest in the comments section:

http://www.cyclingnews.com/news/what-is-fluimucil-and-why-would-wiggins-need-it/

According to Nico:

Nico • 20 hours ago
Fluimucil increases your hematocrit. it's that simple. This is doping.

I can almost guarantee if I were to challenge that I would just be referred to Tuckers tweet. Someone else has commented with a link to the article.


That's a general recommendation, likely given to people self-medicating as a side-effect can cause problems. In reality many people with lung problems are given this drug on a regular basis, it's just necessary to monitor them (which is obviously going to happen with Wiggins). Again, it's a case of people taking the first thing they find and running with it without the knowledge or further investigation.

The real, interesting part of all this is something you've pointed out before and Lawton alludes to. It's ridiculous to expect people to believe it had to come to a parliamentary enquiry for them to reveal that it was acetylcysteine and that DB found that out in one phone call. That's the real issue here but all this chat about the thing they claim was in the package will take away from it.

I read that comment when it was posted. I looked around the google machine to find anything to back up that assertion and could not, but I found a link to a study that shows an actual DECREASE in hematocrit, although the decrease was well below 0.01%. Ultimately I didn't trust anything I was reading because again I don't really understand medical mumbo jumbo as well as others such as KB, so I kept it to myself.

 

[King Boonen]

Re:

I had a quick look. There are a fair few problems but the biggest is that there is no baseline data for the groups. Without it it's impossible to draw the conclusions they have done.

Why you do not like those conclusions? You say there are no baselines but their approach is not comparing measurements against the baselines. It is important to realise that CNAC and NAC are the same people. They took 15 people and did the first test during 8 days. Then they allowed for "wash-out" 3-week period and did the second test. They do not mention whether the first test was with NAC and the second with placebo, or vice versa, but let's assume results are not affected by the sequence.

So what they actually measured was that the same people had different blood values after taking NAC than they had after taking placebo. Isn't it then a fair conclusion that NAC had some effect on the blood? The measurements they did after trial with placebo can in fact be considered as the baseline you were missing, no?

No, they can't, for several reasons:

1) You cannot use the same participants for case and control in a double blind study, it's impossible and means that either it was singly blind, open or they don't actually know what they were doing.

2) They do not specifically state the order but they state the wash out period occurred between thiol and placebo treatment. This implies that the thiol treatment happened first and as such they have no baseline data.

3) They have no baseline data for the control/placebo study and you can't just assume it has no effect, you actually have to show that. Again, this means they have no baseline data for their NAC experiment.

These three things alone completely invalidate the conclusions. There is also the small size of the groups to take into account.

The numbers they report seem strange too, although this isn't my area. They show a higher hematocrit and EPO but lower RBC counts which doesn't make sense based on my understanding. The MCV has increased which is what has increased the hematocrit, but at they haven't assessed the Hb-O2 we have not idea if that would even have an effect on exercise (not the point of the study but it is the conclusion people are drawing). They don't address the change in MCV in the discussion. If these are the same people that would be something that really needs addressing.

They haven't assessed the exercise performance so I don't really understand the point of including it, maybe I'm missing it?

Honestly, it reads like a final year project that was written up as a paper. This isn't a problem, the problem is people taking the results and drawing conclusions that really can't be drawn. This is compounded when a respected scientist highlights the work as people who don't really understand it will assume it's right.

It was a crossover design wasn't it ? (or two crossovers). What you wrote in 1) and 2) doesn't apply unless I misunderstand. Agree it would be nice to see baseline results for start of each period just to confirm randomization and sufficient washout but I don't see that as reason to dismiss the results necessarily

That's what they claim, but they also claim it was double blind and it can't be both. 2) would still apply unless they had done a previous study to show there were no long term effects of acetylcysteine treatment which I can't find. 3) alone invalidates it, you cannot assume the placebo does nothing.

It is a small, poorly designed study that, at best, could be used to suggest further investigation.

 

[Eyeballs Out]

Re: Re:

I had a quick look. There are a fair few problems but the biggest is that there is no baseline data for the groups. Without it it's impossible to draw the conclusions they have done.

Why you do not like those conclusions? You say there are no baselines but their approach is not comparing measurements against the baselines. It is important to realise that CNAC and NAC are the same people. They took 15 people and did the first test during 8 days. Then they allowed for "wash-out" 3-week period and did the second test. They do not mention whether the first test was with NAC and the second with placebo, or vice versa, but let's assume results are not affected by the sequence.

So what they actually measured was that the same people had different blood values after taking NAC than they had after taking placebo. Isn't it then a fair conclusion that NAC had some effect on the blood? The measurements they did after trial with placebo can in fact be considered as the baseline you were missing, no?

No, they can't, for several reasons:

1) You cannot use the same participants for case and control in a double blind study, it's impossible and means that either it was singly blind, open or they don't actually know what they were doing.

2) They do not specifically state the order but they state the wash out period occurred between thiol and placebo treatment. This implies that the thiol treatment happened first and as such they have no baseline data.

3) They have no baseline data for the control/placebo study and you can't just assume it has no effect, you actually have to show that. Again, this means they have no baseline data for their NAC experiment.

These three things alone completely invalidate the conclusions. There is also the small size of the groups to take into account.

The numbers they report seem strange too, although this isn't my area. They show a higher hematocrit and EPO but lower RBC counts which doesn't make sense based on my understanding. The MCV has increased which is what has increased the hematocrit, but at they haven't assessed the Hb-O2 we have not idea if that would even have an effect on exercise (not the point of the study but it is the conclusion people are drawing). They don't address the change in MCV in the discussion. If these are the same people that would be something that really needs addressing.

They haven't assessed the exercise performance so I don't really understand the point of including it, maybe I'm missing it?

Honestly, it reads like a final year project that was written up as a paper. This isn't a problem, the problem is people taking the results and drawing conclusions that really can't be drawn. This is compounded when a respected scientist highlights the work as people who don't really understand it will assume it's right.

It was a crossover design wasn't it ? (or two crossovers). What you wrote in 1) and 2) doesn't apply unless I misunderstand. Agree it would be nice to see baseline results for start of each period just to confirm randomization and sufficient washout but I don't see that as reason to dismiss the results necessarily

That's what they claim, but they also claim it was double blind and it can't be both. 2) would still apply unless they had done a previous study to show there were no long term effects of acetylcysteine treatment which I can't find. 3) alone invalidates it, you cannot assume the placebo does nothing.

It is a small, poorly designed study that, at best, could be used to suggest further investigation.

There is no reason a crossover cannot be double-blind - just depends whether you can have a treatment that appears same as placebo. So no problem if it is a tablet or injection. Maybe a problem if it's surgery. And re 2) of course in crossover, the order depends on the randomization

 

[King Boonen]

Re: Re:

There is no reason a crossover cannot be double-blind - just depends whether you can have a treatment that appears same as placebo. So no problem if it is a tablet or injection. Maybe a problem if it's surgery. And re 2) of course in crossover, the order depends on the randomization

Fair point, I think I get that, cheers. I'm assuming pot A and pot B then switch with no-one knowing which is which? My main problem was, and still is, and that is there is still no baseline data so there is no way they can claim a change.

 

[Eyeballs Out]

Re: Re:

There is no reason a crossover cannot be double-blind - just depends whether you can have a treatment that appears same as placebo. So no problem if it is a tablet or injection. Maybe a problem if it's surgery. And re 2) of course in crossover, the order depends on the randomization

Fair point, I think I get that, but there is still no baseline data so there is no way they can claim a change.

I think they can claim it for this study. Or to put it another way, I'm struggling to think of a good reason why you would see such a consistently significant increase across most of the hem parameters with one treatment and consistently no change with the another treatment. Only that do a trial enough times and you will see a significant result eventually - that's all I've got.

 

[King Boonen]

Re: Re:

There is no reason a crossover cannot be double-blind - just depends whether you can have a treatment that appears same as placebo. So no problem if it is a tablet or injection. Maybe a problem if it's surgery. And re 2) of course in crossover, the order depends on the randomization

Fair point, I think I get that, but there is still no baseline data so there is no way they can claim a change.

I think they can claim it for this study. Or to put it another way, I'm struggling to think of a good reason why you would see such a consistently significant increase across most of the hem parameters with one treatment and consistently no change with the another treatment. Only that do a trial enough times and you will see a significant result eventually - that's all I've got.

You don't see a change or no change though as you don't have a baseline result to compare it to. You are assuming that the control is no change, maybe it's actually a decrease?

 

[djpbaltimore]

And there is still the matter of the small sample size. If you have a lot of parameters and a smallish group of people to test, some of it will invariably show 'significance'. Remember the study that showed that chocolate enhances weight loss.

I know what you’re thinking. The study did show accelerated weight loss in the chocolate group—shouldn’t we trust it? Isn’t that how science works? Here’s a dirty little science secret: If you measure a large number of things about a small number of people, you are almost guaranteed to get a “statistically significant” result. Our study included 18 different measurements—weight, cholesterol, sodium, blood protein levels, sleep quality, well-being, etc.—from 15 people.

http://io9.gizmodo.com/i-fooled-millions-into-thinking-chocolate-helps-weight-1707251800

 

[PeterB]

Regarding the discussed study I am happy to admit that it probably does not meet highest academic standards. Yet it was accepted for publication in a journal of the State Academy of Sciences of the Czech Rep., so who are we to claim it is useless? (I do not know about all of you others just that I am fine accepting that authority of the editors on these matters is higher than mine).

Regarding no testing of effects of the placebo in that study, is it really at all imaginable that lactose dissolved in water can have effect on your Hb or Hct levels, other than pure water?

I also looked up other papers concerning various effects of NAC related to performance on the internet and there actually seems to be quite a lot of them. No wonder this substance was tried also by other teams. Since it was not prohibited and since various researches at least suggested potential positive effect, I can see incentive for trying it. A few quotes from various papers:
"In conclusion, NAC significantly attenuated the percentage decline in maximal Na+,K+-pump activity during submaximal fatiguing exercise..."
"Together these suggest that enhanced muscle K+ regulation with NAC likely contributed to the substantial increase in time to fatigue during prolonged submaximal exercise in these well-trained individuals."
But also "Finally, NAC infusion did not enhance performance during voluntary, high-intensity, intermittent cycling exercise in humans."

So the research seems to be still ongoing and those who believe it may be helpful (or have access to yet unpublished research) simply take it, they are free and allowed to do so, after all. But I am really curious what comes out of this seeing the hystery around...

 

[King Boonen]

PeterB, honestly it's about as imaginable as acetylcysteine, hence the massive akepticism.

As for the journal, rubbish gets published, even in good journals. I can point you to a retracted Nature paper on Plasmodium that should never have been published in the first place.

 

[djpbaltimore]

Re: Re:

No, they can't, for several reasons:

1) You cannot use the same participants for case and control in a double blind study, it's impossible and means that either it was singly blind, open or they don't actually know what they were doing.

2) They do not specifically state the order but they state the wash out period occurred between thiol and placebo treatment. This implies that the thiol treatment happened first and as such they have no baseline data.

3) They have no baseline data for the control/placebo study and you can't just assume it has no effect, you actually have to show that. Again, this means they have no baseline data for their NAC experiment.

These three things alone completely invalidate the conclusions. There is also the small size of the groups to take into account.

The numbers they report seem strange too, although this isn't my area. They show a higher hematocrit and EPO but lower RBC counts which doesn't make sense based on my understanding. The MCV has increased which is what has increased the hematocrit, but at they haven't assessed the Hb-O2 we have not idea if that would even have an effect on exercise (not the point of the study but it is the conclusion people are drawing). They don't address the change in MCV in the discussion. If these are the same people that would be something that really needs addressing.

They haven't assessed the exercise performance so I don't really understand the point of including it, maybe I'm missing it?

Honestly, it reads like a final year project that was written up as a paper. This isn't a problem, the problem is people taking the results and drawing conclusions that really can't be drawn. This is compounded when a respected scientist highlights the work as people who don't really understand it will assume it's right.

I think this is their followup work. It showed no significant increase in performance.

The mean VO2max in CON and NAC groups were 48.50 ± 5.16 and 47.74 ± 5.47 ml kg−1 min−1, respectively. The maximal heart rates were 191.9 ± 6.9 and 189.9 ± 8.8 beats min−1, post-exercise lactate concentrations were 10.85 ± 2.31 and 11.63 ± 2.28 mmol l−1. The time to fatigue (CON 17.24 ± 1.73 min, NAC 17.64 ± 1.65 min) and maximal workload (CON 168.63 ± 14.84 W, NAC 171.31 ± 14.94 W) tended to higher values, however, the differences were not statistically significant.

http://link.springer.com/article/10.1007%2Fs13105-010-0002-1

 

[PeterB]

Re:

PeterB, honestly it's about as imaginable as acetylcysteine, hence the massive akepticism.

As for the journal, rubbish gets published, even in good journals. I can point you to a retracted Nature paper on Plasmodium that should never have been published in the first place.

I believe this stuff happens. It's just this strange era when suddenly anyone is free to dispute and reject sources that should normally bear quite a high degree of credibility and guarantee that information you obtain from them has real validity. It can be quite dangerous if society decides that opinion of the knowledgeable sources no longer matters...

 

[Eyeballs Out]

Re: Re:

There is no reason a crossover cannot be double-blind - just depends whether you can have a treatment that appears same as placebo. So no problem if it is a tablet or injection. Maybe a problem if it's surgery. And re 2) of course in crossover, the order depends on the randomization

Fair point, I think I get that, but there is still no baseline data so there is no way they can claim a change.

I think they can claim it for this study. Or to put it another way, I'm struggling to think of a good reason why you would see such a consistently significant increase across most of the hem parameters with one treatment and consistently no change with the another treatment. Only that do a trial enough times and you will see a significant result eventually - that's all I've got.

You don't see a change or no change though as you don't have a baseline result to compare it to. You are assuming that the control is no change, maybe it's actually a decrease?

Well that is an implicit assumption for placebo-controlled studies - that the placebo has little or no effect- otherwise they would be pointless. OK there is the well-documented "placebo" effect but that tends to reduce treatment difference, not increase it. Anyway this is all a bit off-topic

 

[King Boonen]

Re: Re:

There is no reason a crossover cannot be double-blind - just depends whether you can have a treatment that appears same as placebo. So no problem if it is a tablet or injection. Maybe a problem if it's surgery. And re 2) of course in crossover, the order depends on the randomization

Fair point, I think I get that, but there is still no baseline data so there is no way they can claim a change.

I think they can claim it for this study. Or to put it another way, I'm struggling to think of a good reason why you would see such a consistently significant increase across most of the hem parameters with one treatment and consistently no change with the another treatment. Only that do a trial enough times and you will see a significant result eventually - that's all I've got.

You don't see a change or no change though as you don't have a baseline result to compare it to. You are assuming that the control is no change, maybe it's actually a decrease?

Well that is an implicit assumption for placebo-controlled studies - that the placebo has little or no effect- otherwise they would be pointless. OK there is the well-documented "placebo" effect but that tends to reduce treatment difference, not increase it. Anyway this is all a bit off-topic

I don't believe it is ever assumed, that's why you have a placebo/control group and the required data point. We certainly do this, even when we have done the same thing before. They do not exist here. They can report a difference between their groups but they cannot infer a change without that data. If they had it we then move on to the other problems.

The placebo effect is an interesting dosscusion, it's likely just regression to the mean in most cases but that really is off-topic.

 

[King Boonen]

Re: Re:

PeterB, honestly it's about as imaginable as acetylcysteine, hence the massive akepticism.

As for the journal, rubbish gets published, even in good journals. I can point you to a retracted Nature paper on Plasmodium that should never have been published in the first place.

I believe this stuff happens. It's just this strange era when suddenly anyone is free to dispute and reject sources that should normally bear quite a high degree of credibility and guarantee that information you obtain from them has real validity. It can be quite dangerous if society decides that opinion of the knowledgeable sources no longer matters...

Anyone should be free to dispute anything, that's the best thing about the digital age. What they should be required to do is show why they disagree, I've done this.

No source should be held on a pedestal, if it's good it should be able to stand up on its own. It's also why many people wish to remain anonymous or not wave qualifications on the internet, a post should stand up on its own no matter who posted it.

 

[Irondan]

Re: Re:

PeterB, honestly it's about as imaginable as acetylcysteine, hence the massive akepticism.

As for the journal, rubbish gets published, even in good journals. I can point you to a retracted Nature paper on Plasmodium that should never have been published in the first place.

I believe this stuff happens. It's just this strange era when suddenly anyone is free to dispute and reject sources that should normally bear quite a high degree of credibility and guarantee that information you obtain from them has real validity. It can be quite dangerous if society decides that opinion of the knowledgeable sources no longer matters...

Anyone should be free to dispute anything, that's the best thing about the digital age. What they should be required to do is show why they disagree, I've done this.

No source should be held on a pedestal, if it's good it should be able to stand up on its own. It's also why many people wish to remain anonymous or not wave qualifications on the internet, a post should stand up on its own no matter who posted it.

Great post KB, I agree completely....

 

[aphronesis]

Re:

PeterB, honestly it's about as imaginable as acetylcysteine, hence the massive akepticism.

As for the journal, rubbish gets published, even in good journals. I can point you to a retracted Nature paper on Plasmodium that should never have been published in the first place.

Yes, publication in today's world, regardless the source, is a criterion on nothing significant--or automatically valid.

Edit: Dan on it.

 

[thehog]

After juicing his performance to levels unseen in his career, Wiggins now cannot be bothered to ever try for a grand tour again. Convenient. Hesjedal was pretty much a joke this season. Even Contador does not seem willing to risk much. Is this the new strategy for doping: Dope yourself to the moon then coast on the results?

Who is next?

Post 1 and BroDeal was proven right!

 

[aphronesis]

You, we, all knew this. The question would be the Brits' handling of it.

 

[Benotti69]

Wonder will Wiggins get a gig as a roadie for Weller when this all over. Might be a good source for 'substances'....

 

[Stingray34]

If you're wondering by now

who Brad Wiggins is

look no further than the mirror

for he is

the greed and fear

and every ounce of hate

in you

 

[Stingray34]

Re:

Wonder will Wiggins get a gig as a roadie for Weller when this all over. Might be a good source for 'substances'....

This is the modern world. A real beat surrender.

See the boy with long tatts

marching across the lawns at midnight.

 

[Stingray34]

Re:

Wonder will Wiggins get a gig as a roadie for Weller when this all over. Might be a good source for 'substances'....

Thing is, Weller and Wiggins are both drunks - any off-licence with a goodly supply of tawny port will do them.

 

[Frankenstorm]

What you think, imminent revelations as to the nature the 'jiffy bag'?

https://www.theguardian.com/sport/2016/dec/28/bradley-wiggins-announces-retirement-from-cycling

 

[Sorped]

Re:

What you think, imminent revelations as to the nature the 'jiffy bag'?

https://www.theguardian.com/sport/2016/dec/28/bradley-wiggins-announces-retirement-from-cycling

My first thought too.