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MAIIA - the new EPO test

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Clausfarre said:
It just seems that history has shown us that with refined tests for doping comes new products and methods. It's an arms race that can only be slowed down in the attitude of the peloton changes. Which it has, if we are to believe certain people.

Not sure though... I usually like to base my optimism on, well, something.

what history has actually shown as is that the fox can't watch the hen house. history's also shown us that even when the foxes reluctantly use slightly more effective, strategic, and well-timed testing a new speed limit can be set.

there's always a need for new and better testing but don't let the comments of overconfident dopers fool you, many of the tools we have to work with at present are quite effective when applied correctly.

show me a governing body motivated to catch people (i don't know of any) and i'll show you a clean sport.

in the long term, independent 3rd party testing and results management are the only option.
 
May 26, 2010
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lean said:
what history has actually shown as is that the fox can't watch the hen house. history's also shown us that even when the foxes reluctantly use slightly more effective, strategic, and well-timed testing a new speed limit can be set.

there's always a need for new and better testing but don't let the comments of overconfident dopers fool you, many of the tools we have to work with at present are quite effective when applied correctly.

show me a governing body motivated to catch people (i don't know of any) and i'll show you a clean sport.

in the long term, independent 3rd party testing and results management are the only option.

+1

10 chara..............
 
Interesting.

The essence is that you cut the testing time from 3 days to 20 minutes...and, you can do mass production, like 20 samples at once instead of one at a time.

Right there is a benefit. Then getting more sensitive testing makes for better testing to build a rider's passport DB.
 
Jan 20, 2013
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lean said:
show me a governing body motivated to catch people (i don't know of any) and i'll show you a clean sport.

in the long term, independent 3rd party testing and results management are the only option.

Exactly right. As long as UCI, with their less than stellar track record, aren't willing to set up independent testing we must doubt their sincerity. I mean, the UCI can set some pretty tough parimeters that the new authority has to meet but I have heard nothing of the kind.

Change Cycling Now put forward the proposal and the UCI does not have to do everything they suggest but AT LEAST, for the sake of the sport, have a dialogue in stead of digging trenches, shooting at everyone. Pat must have his own reasons for being such a control freak.
 
Every 2-4 years, samples from the last 10 years should be tested with whatever relevant new tests have appeared in that time frame.

A positive should be taken as any other adverse analytical finding and bans issued, with loss of results from the date of the sample being taken to the date of the adverse analytical finding. Along with repayment of prize money etc...

Doesn't matter if the sample is a week old or 10 years old. Lose everything between that date and the time the test is run.

That should put a suitable climate of fear around risking dodgy substances.
 
Sep 22, 2012
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Catwhoorg said:
Every 2-4 years, samples from the last 10 years should be tested with whatever relevant new tests have appeared in that time frame.

A positive should be taken as any other adverse analytical finding and bans issued, with loss of results from the date of the sample being taken to the date of the adverse analytical finding. Along with repayment of prize money etc...

Doesn't matter if the sample is a week old or 10 years old. Lose everything between that date and the time the test is run.

That should put a suitable climate of fear around risking dodgy substances.

Sounds good.
 
Jan 20, 2013
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Catwhoorg said:
Every 2-4 years, samples from the last 10 years should be tested with whatever relevant new tests have appeared in that time frame.

A positive should be taken as any other adverse analytical finding and bans issued, with loss of results from the date of the sample being taken to the date of the adverse analytical finding. Along with repayment of prize money etc...

Doesn't matter if the sample is a week old or 10 years old. Lose everything between that date and the time the test is run.

That should put a suitable climate of fear around risking dodgy substances.

Right on. Not having a working method of detection should not matter and statutes of limitations should reflect this. No reason to be tolerant anymore.
 
Mar 10, 2009
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Krebs cycle said:
Well it is a great advance because microdosing is only effective if you're having injections everyday or every 2nd day for weeks or months at a time. If your "glowtime" increases from 12 to 72hrs that means the risk of going +ve during out of competition testing is dramatically increased.

A great advance like the marker in CERA, now they switch to a new method. As for the micro dosing I'm sure even if they use it ever 3+N days they will still benefit more than those without it.

The test itself seems a great advance. Whether or not that is linked to more effective out of competition testing in conjunction with strictly enforcing the "3 strikes and you're out rule" is the real issue. A few years ago Michael Ashenden suggested GPS tracking as a mean to improve athlete whereabouts. At the time it got shouted down as being too invasive to privacy. Pro cycling has been such a naughty little boy however that IMO they gave that right up.

GPS track every one of them. Target most of your resources on random surprise tests in the 4 weeks leading up to the biggest races. 3 no shows and you get an instant 2yr ban.

edit: in particular... hit them with tests whenever they go to remote, out of the way locations on team training camps!

So if an athlete gets his PED's home delivered, what then? Camera mounted on his front door? GPS tracking also has its flaws, don't think so turn it on on your phone and see how accurate it is, I'm sure you can find a plethora of tracking apps to use.
 
ElChingon said:
A great advance like the marker in CERA, now they switch to a new method. As for the micro dosing I'm sure even if they use it ever 3+N days they will still benefit more than those without it..
They'd switch to a new method, yes. Typically, a less efficient one. They would still get an unfair advantage, but theoretically, at some point, if you reduce that advantage enough it stops being worth the risk.
 
Update on this test and the methods used for anyone who is interested. I downloaded the fulltext versions of the actual paper published in Scand J Med Sci Sports.....

The study by Morkeberg used the following protocol:

2 injections 50 IU/kg per week for 3 weeks followed by 2 injections per week 10 IU/kg bw.

Results: high sensitivity 12hr after 10 IU/kg doses
high sensitivity 72 hrs after 50 IU/kg doses

Author's conclusion: good sensitivity 24-48hr after even the 10 IU/kg doses


The study by Ashenden which is discussed here http://forum.cyclingnews.com/showthread.php?t=19011 used the following protocol....

2 injections per week:
10 IU/kg for 4 weeks (Phase I)
20 IU/kg for 4 weeks (phase II)
30 IU/kg for 4 weeks (phase III)

Importantly, this study did NOT examine urine samples. They only looked at the blood data. This last point is really important because the MAIIA test is a urine test. What we can see from this is that the doses required to increase total Hbmass by 10% or so would get flagged by the urine test for 72hrs (esp in later phases where the doses are increasing). If you are taking a dose twice weekly, then during phase 4 you would test positive almost 100% of the time.

The increase in total Hbmass after phase I was 2.6% (25g total). You can get larger increases than that from using an altitude chamber though. Such a small increase in Hbmass is a big risk to take when you still might test positive 24-48hrs after a dose of EPO and you could achieve the same by perfectly legal means.

The problem is simple. Blood tests and urine samples must always be collected together at the same time.
 
ElChingon said:
So if an athlete gets his PED's home delivered, what then? Camera mounted on his front door? GPS tracking also has its flaws, don't think so turn it on on your phone and see how accurate it is, I'm sure you can find a plethora of tracking apps to use.

The GPS suggestion Ashendon originally put forth was so that athletes could always be found for out of competition testing. At present, the current whereabouts sysyem can be circumvented. Dodging doping control officers is still possible and effective. It's a real problem with OOC sample collection. It wasn't meant to facilitate around the clock surveillance.
 
Catwhoorg said:
Every 2-4 years, samples from the last 10 years should be tested with whatever relevant new tests have appeared in that time frame.

Agree.

But, How about faster testing and repercussions...

Fail. No renewed licence for the following year.

People then would learn quick.

Feed the family, or don't.

Protect a generation.

i.e. an effective and administered test enables everyone to believe in the sport.

~ Sir Logical
 
ElChingon said:
A great advance like the marker in CERA, now they switch to a new method. As for the micro dosing I'm sure even if they use it ever 3+N days they will still benefit more than those without it.



So if an athlete gets his PED's home delivered, what then? Camera mounted on his front door? GPS tracking also has its flaws, don't think so turn it on on your phone and see how accurate it is, I'm sure you can find a plethora of tracking apps to use.
Just putting enough hurdles to either discourage dopers or reduce their advantage. Doing nothing won't help us.
 
Mar 4, 2010
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Krebs cycle said:
Update on this test and the methods used for anyone who is interested. I downloaded the fulltext versions of the actual paper published in Scand J Med Sci Sports.....

The study by Morkeberg used the following protocol:

2 injections 50 IU/kg per week for 3 weeks followed by 2 injections per week 10 IU/kg bw.

Results: high sensitivity 12hr after 10 IU/kg doses
high sensitivity 72 hrs after 50 IU/kg doses

Author's conclusion: good sensitivity 24-48hr after even the 10 IU/kg doses


The study by Ashenden which is discussed here http://forum.cyclingnews.com/showthread.php?t=19011 used the following protocol....

2 injections per week:
10 IU/kg for 4 weeks (Phase I)
20 IU/kg for 4 weeks (phase II)
30 IU/kg for 4 weeks (phase III)

Importantly, this study did NOT examine urine samples. They only looked at the blood data. This last point is really important because the MAIIA test is a urine test. What we can see from this is that the doses required to increase total Hbmass by 10% or so would get flagged by the urine test for 72hrs (esp in later phases where the doses are increasing). If you are taking a dose twice weekly, then during phase 4 you would test positive almost 100% of the time.

The increase in total Hbmass after phase I was 2.6% (25g total). You can get larger increases than that from using an altitude chamber though. Such a small increase in Hbmass is a big risk to take when you still might test positive 24-48hrs after a dose of EPO and you could achieve the same by perfectly legal means.

The problem is simple. Blood tests and urine samples must always be collected together at the same time.

Am I wrong in thinking anything after phase 1 would leave you glowing the day after a micro-dose even with the current test? We know Lance had a borderline positive doing 800 iu IV and trying to mask it with altitude.
 
Sep 29, 2012
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Tyler'sTwin said:
Am I wrong in thinking anything after phase 1 would leave you glowing the day after a micro-dose even with the current test? We know Lance had a borderline positive doing 800 iu IV and trying to mask it with altitude.

Given the average OOC tests were 2/rider, I'd say the best time to charge would be right after the tester leaves for that first OOC test for the year.
 
Oct 8, 2010
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So, re: this new test, which is rumored to be used to detect epo microdosing. Did you now that Danishefsky recently developed a chemical synthesis for homogeneous erythropoietin. this form of EPO is totally undetectable/indistinguishable from natural EPO by all currently known methods.
Currently too expensive and academic to be applied in a PED context, but it's only a question of time. :eek:

With undetectable epo and undetectable transfusions, it would be child's play to do ridiculous stuff & still have a nice ABP & no positive tests, i'd say.
 
Oct 8, 2010
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It is fully undetectable to the EPO test, because it shows up as natural. The biological effects are the same, so everything that would show up with regular EPO on the irregularities ABP would also show up with this. However, there are ways to manipulate the values. I'm no expert on the passport, but I remember reading that you can tune your reticulocyte count value to believable values if you combine transfusions & epo in the right way. This interview with Ashendenseems to confirm this

And right now it's expensive as in: never scaled up, only ever performed by one academic lab and expertise needed for synthesis. So you right now, you would need 100.000's of $ + the goodwill of the researchers for things that would amount to just a few doses.
 
Jan 18, 2010
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easier to detect?

Since the chemically synthesized EPO is a single molecular species (i.e. one isoform) it should be easily detectable.

Even if that isoform is identical to a naturally produced human isoform, adding it exogenously should lead to an unnatural abundance of one isoform over the rest. This will change the distribution of natural isoforms present, so if testers know to look for it, they should be able to see this difference.
 
Sep 29, 2012
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biokemguy said:
Since the chemically synthesized EPO is a single molecular species (i.e. one isoform) it should be easily detectable.

Even if that isoform is identical to a naturally produced human isoform, adding it exogenously should lead to an unnatural abundance of one isoform over the rest. This will change the distribution of natural isoforms present, so if testers know to look for it, they should be able to see this difference.

If the concentration of an isoform is higher (as would be the case when exogenous EPO is present in the system), how does that appear? Does a particular band simply go darker?

If so, that seems to be a bit of subjective pot luck as to whether they can determine a change from baseline - given they will not have previous isoform images on hand for comparison. Or do they?
 
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Yeah, I would expect a single band to go darker, but it doesn't need to be a subjective judgement about the darkness of a band.

This can be quantified using densitometry with some standards run on each gel. The trick is figuring out what the distribution in a non-doped person is, but that may already be in the literature (I haven't looked for it).

If it's not in the literature, there should be plenty of data available from previous tests on athletes that are clean. (Yes I think they exist)

I'm sure the lab techs that run these tests can tell the difference between definitely clean and borderline results that are defined as an analytical negative even though there's a little bit of exogenous EPO present.
 
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biokemguy said:
Yeah, I would expect a single band to go darker, but it doesn't need to be a subjective judgement about the darkness of a band.

This can be quantified using densitometry with some standards run on each gel. The trick is figuring out what the distribution in a non-doped person is, but that may already be in the literature (I haven't looked for it).

If it's not in the literature, there should be plenty of data available from previous tests on athletes that are clean. (Yes I think they exist)

I'm sure the lab techs that run these tests can tell the difference between definitely clean and borderline results that are defined as an analytical negative even though there's a little bit of exogenous EPO present.

I seem to recall that distribution of EPO isoforms is pretty variable over time and also between different people. (sorry only source for this claim ican give right now is Schänzer et al Sport Und Buch Strauss, Köln (2004) 309-316).

The way the MAIIA test is used right now in the ashenden and morkeberg papers it will not be noticed if there was no variability. I also think that saying with certainty that levels of one isoform are raised in a suspicious amount will be VERY hard, because of overlap with natural bands. Maybe in combination with an carbon isotope ratio it would be possible?

But in principle I agree with your remarks.

I am no analytical chemist by training (my specialty is organic/medchem ), so I hope I'm not missing something. I welcome further remarks!
 
Sep 29, 2012
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biokemguy said:
Yeah, I would expect a single band to go darker, but it doesn't need to be a subjective judgement about the darkness of a band.

This can be quantified using densitometry with some standards run on each gel. The trick is figuring out what the distribution in a non-doped person is, but that may already be in the literature (I haven't looked for it).

If it's not in the literature, there should be plenty of data available from previous tests on athletes that are clean. (Yes I think they exist)

I'm sure the lab techs that run these tests can tell the difference between definitely clean and borderline results that are defined as an analytical negative even though there's a little bit of exogenous EPO present.

saugy could / can (tour de suisse 2001), so yes, others can, but it's demonstrably non-binary and false positive avoidance is the main focus with a new test.