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Innovative Anti Doping Tests

At the American Open Series 3, Dried Blood Spot (DBS) testing will be deployed. Using TAP™, the world’s first push-button blood collection device fromSeventh Sense Biosystems, Inc. (7SBio), the DBS pilot program will make it possible to gather more athlete samples while also greatly reducing the human and financial resources required to conduct tests. DBS testing also allows greater ease storing samples for future re-analysis.

This pilot program, together with existing allocations of blood and urine testing, will mean that the event will be the most tested event in USA Weightlifting history, further showing the commitment of bothUSA Weightlifting and USADA to provide a fair platform to athletes.
link
What is Dried Blood Spot (DBS) Testing?

DBS testing is another method, like traditional urine and blood testing, designed to detect and deter the use of substances and methods on the World Anti-Doping Agency (WADA) Prohibited List. DBS is also being investigated as a collection method that can measure important biomarkers that may be indicative of doping.

Moreover, DBS testing makes it easier to transport blood samples to WADA-accredited laboratories, and provides additional sample stability in storage for future analysis.

What is the TAP and how does it work?

The TAP is a new FDA-approved blood collection device that is positioned on the surface of an athlete’s upper arm or other limb. With the push of a button, the blood sample is collected from the surface of the skin and securely stored within the device. The collection process typically takes less than five minutes and can be completed by your DCO.

Will the device leave a mark or cause any side effects?

The device collects about 20 times less blood than normally collected in a single vial during venipuncture. There are no known health implications or side effects associated with the TAP.

At most, the TAP device will leave a small ring where it was applied to the athlete’s arm. The new collection process should be quick and virtually pain-free.

Will this method replace the current intravenous (venipuncture) collection method?

DBS testing will become an additional blood collection method, and traditional venipuncture collections will continue to be used. Occasionally, athletes will experience both collection methods during one test session. This should not impact performance because the TAP collects just five drops of blood.
 
ClassicomanoLuigi said:
Another interesting find, FMK. What's the verdict of the Clinicians on this one? This minimalist, "pain-free" blood testing sounded a lot like Theranos...
Theranos did come to mind, yes. I think my bigger concern would be how much testing could actually be done, not just immediately, but in the future if we are to believe that storing samples is the way to let technology catch up with cheating methods. KingBoonen, you got any ideas?
 
I have had only a precursory look at the article and haven't read it in too much detail yet, but here is a brand new article about a relatively new approach to detect autotransfusions:

https://cyclingtips.com/2018/08/game-changer-the-long-push-to-end-blood-transfusions-in-sport/

The research has been going on for a few years and while the approach has had some problems and there hasn't been (yet) a breakthrough, I know for sure that none-other-than Dr. Björn Ekblom (who "developed" blood doping in the late-1960's) is about 100 % certain that the method will eventually catch the blood dopers.
 
ClassicomanoLuigi said:
Jeff Novitzsky introduces the DBS tap on Joe Rogan show

https://www.youtube.com/watch?v=-xxfT301Ii8&t=2h11m20s

at 2 hours 11 minutes 20 seconds

This makes a lot of sense for the mass-spectroscopy for MMA and weightlifting where the steroids and many of the other drugs of abuse can be easily detected
That's quite interesting actually. Thanks.

I see from the WADA research page that there's been several funded projects looking into it, all coming from Cologne university:

 
Aragon said:
I have had only a precursory look at the article and haven't read it in too much detail yet, but here is a brand new article about a relatively new approach to detect autotransfusions:

https://cyclingtips.com/2018/08/game-changer-the-long-push-to-end-blood-transfusions-in-sport/

The research has been going on for a few years and while the approach has had some problems and there hasn't been (yet) a breakthrough, I know for sure that none-other-than Dr. Björn Ekblom (who "developed" blood doping in the late-1960's) is about 100 % certain that the method will eventually catch the blood dopers.
After the many journalists who fell in love with Yannis Pitsiladis I find it hard not to be somewhat sceptical of these projects, especially at such an early stage and with so many hurdles to overcome. That said, if it comes good, it's interesting. Will definitely be keeping an eye out for further developments.

However. A question: is there much in terms of evidence that this is a real problem, either in general or within cycling? Yes, at the lower levels we're still popping people for EPO and related substances, but at the top end of the sport, how much of an influence do we think this still is? Yes, the ABP is beatable, that's long been known but if it's being beaten on a large scale, why are so few cocking it all up or just getting unlucky with teh timing of a test?
“If you do it wrong or too close to testing, or if you use a high dose of EPO, then of course you change your concentrations of red blood cells and concentrations of haemoglobin. And that’s definitely going to show up on the passport. But I also think if you know what you’re doing, you can fly under the radar.”
The Kreuziger case as an explanation - as used by Stokes - sounds like a lot of typical anti-doping 'logic': they're not catching the people because they don't want to.
 
It is indeed difficult to evaluate how "game changer" the test would be without knowing how prevalent the use of autotransfusions are and whether cyclists would only be switching to some alternative blood doping strategy would the test be implemented.

And one should be super-skeptical whenever a scientist sees a huge problem and he is the chosen one who has the key to solve it, because despite Ekblom's enthusiasm, this might turn out to be yet still another false hope, and for the last 20-40 years the doping testers wanting more funding have regularly seen the paradise right around the corner with some new fancy method + lucrative funding + "a few years to finish the research".

One example of some over-the-top claims in the article is that the quoted 17 % increase in Vo2Max is just hyperbole, because it is the "overnight" increase that took place when the donated blood was reinfused. This doesn't mean that blood doping increases Vo2Max by 17 %, because if one actually reads the study, the Vo2Max increase was more modest when compared to the starting point and the transfused group only more-or-less recovered to the original figure:
Compared to Control, running time to exhaustion was decreased after blood donation, and increased 48 h after RBC re-infusion. Blood donation decreased VO2max for 16 week, and RBC re-infusion increased VO2max for 2–4 weeks, as compared to Control. Compared to initial values, mean value for groups did not changed significantly, neither for running time to exhaustion, nor for VO2max.
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0156157

It would be interesting to know the source for claim about autotransfusions that "it is likely that it was used by some in pro cycling during [the 1970's]", because just recently I found out that a professional cycling team contacted Ekblom in 1971 inquiring whether the doctor would be interested in providing his know-how + in order to blood dope their cyclists.
 
Aragon said:
It would be interesting to know the source for claim about autotransfusions that "it is likely that it was used by some in pro cycling during [the 1970's]", because just recently I found out that a professional cycling team contacted Ekblom in 1971 inquiring whether the doctor would be interested in providing his know-how + in order to blood dope their cyclists.
Given that that's Shane Stokes, I wouldn't hold your breath waiting for a reliable source to be produced, that's likely to be no more than the usual stories about Nencini and Anquetil, with maybe knowledge of Merckx and Zoetemelk added to it.

The professional cycling team was top tier or local to Ekblom? If the former, would you be thinking Italy-based?

WRT Malm's research, I do feel lousy being cynical about it, and it does offer new alternatives, but our experience on these things does lead us to question.
 
fmk_RoI said:
Given that that's Shane Stokes, I wouldn't hold your breath waiting for a reliable source to be produced, that's likely to be no more than the usual stories about Nencini and Anquetil, with maybe knowledge of Merckx and Zoetemelk added to it.

The professional cycling team was top tier or local to Ekblom? If the former, would you be thinking Italy based
I don't know the team nor even the country, all I know is that when he discussed the matter in the media in 1971, Ekblom revealed that he was offered 100.000 krona had he assisted (some unspecified) athletic people with the method. By going through my research file, I noticed that when the issue emerged once again some ten years later, one journalist in friendly terms with him described that the method had its roots in September 1971 and mentioned in passing that Ekblom was offered "six figure amount" for his help by a professional cycling team.

My reading is that they were describing the same incident, but to tell the truth, it isn't like 100 % certain that this actually is the case.

While I have a high opinion about Ekblom, it naturally would've been interesting if the team was Ferretti, because Gösta Pettersson from that team had became the only Swedish winner of Giro only a some months before the existence of blood doping was revealed and as an interesting detail, Pettersson was in familiar terms with Ekblom having visited the GIH-laboratory around 1966-1967 when Ekblom coauthored a paper about cardiovascular functions of athletes when it was revealed that Petterson's Vo2Max was 81.1 ml/kg/min and his stroke volume was enormous.
 
fmk_RoI said:
ClassicomanoLuigi said:
Another interesting find, FMK. What's the verdict of the Clinicians on this one? This minimalist, "pain-free" blood testing sounded a lot like Theranos...
Theranos did come to mind, yes. I think my bigger concern would be how much testing could actually be done, not just immediately, but in the future if we are to believe that storing samples is the way to let technology catch up with cheating methods. KingBoonen, you got any ideas?

Late to the party on this one.

The problem with Theranos, as has been highlighted, was their claim that they had some new wonder machine that allowed tests for everything on less blood than you get from a pin-***. I seem to remember we discussed this at the time and most, if not all, were very dubious about their claims. DBS is different as it isn't a testing method in itself, it's just a way to store the sample.

DBS has a few issues over normal blood sample collection. The volume is small, it needs to be eluted from the media or analysed in situ and this all adds steps that can reduce the sensitivity of the test. It's not surprising that many of the tests discussed are for doping products that have no allowable limit, good limits of detection in normal samples and don't require much quantitation. For this I think it could work very well, DBS is already used as a sampling method in healthcare (most countries use it for disease screening in newborns covering cystic fibrosis, sickle cell disease, several metabolic disorders and hyperthyroidism) so it's mature enough that it should stand up to scrutiny provided the proper protocols are in place.

There are clear benefits to using DBS as collecting the samples does not require a trained phlebotomist and it should be easy to design a device that makes the chain of custody robust (I'm assuming this is what the TAP+ thingy described does). It should also be very easy to store the samples for future testing, I don't think you even require freezers, you just need what is basically a secure card catalogue. Add to that the testing is much, much less invasive. I've had cannulas inserted for a good few experiments in the past to the point I'm quite used to it and it can still induce slight hyperventilation in me, removing the need for these or needles is no bad thing at all. The small amount of material does mean any future testing will have to be sensitive enough to make use of the cards, which generally means several years/decades after a less sensitive test is developed and the instrumentation improves. With this in mind I hope there isn't a wholesale push towards DBS as a cheap option at the expense of normal blood samples.As for detecting more specialist methods of doping such as EPO, CERA, transfusions etc. it's highly unlikely it'll help at the moment or even i the foreseeable future.


The testing for autologous blood transfusions is interesting. Without throughly reading the literature it's hard to know what they are looking for to create their screen. It is possible they are looking at levels of specific proteins, or they may be looking at levels of post-translational-modifications (PTMs). PTMs might be interesting, because if you can find proteins that exhibit specific, reproducible patterns for different PTMs under certain conditions, you may then be able to look for those PTMs that shouldn't be present but are due to an autologous transfusion. The issue would be finding a robust pattern influenced by a transfusion and that PTMs can be short-lived. Looking purely at the levels of specific proteins may be hard, you need a baseline that can be applied across a population and this isn't always possible. Based on the report and making some assumptions due to who they word things, I think they have found a difference in their proteomic data between their treatment and controls, but they don't know what that difference is. They're working on finding out what component/s are causing it and limiting down the test to reproducible signal/s. This is usually the hardest part and without seeing the models they built to assess the data it's hard to have any handle on how successful it might be.

I don't want to sound cynical either, especially as I've not seen any of the data, but I will point out that once you've looked at genomic and transcriptomic data and that hasn't worked, the next logical step is proteomic data, so it's possible this research is more following a general trend, rather than being guided by a biological hypothesis. It's also very possible they have a good idea what they are looking for, they know it's very likely to work and they are spending the time refining it to ensure robust results. We can all hope for the later.


As to how much of an effect such a test will have on the pro peloton, I'd guess very little at WT, increasing down the ranks. The no needles policy and increased testing must make it harder to transfuse and the process is longer than injecting mircera or whatever the current product of choice is. I would think that transfusions are fairly low down the pecking order. That's just supposition though.
 
Another quick point/question. I don't see mention of positive controls in the article (and I didn't really expect it, hence why this is a question). A brief scanning of the paper I see Aragon posted (thanks!), and I mean brief, literally 5 seconds, and I only see control Vs. transfusion. I'm not sure what the positive control would be without knowing what they are looking at, but this is where things like this have a high probability of falling over. It's possible they don't need one, can anyone think of one? (reading more, altitude would be an obvious one). It's something to be aware of.
 
What is the TAP and how does it work?

The TAP is a new FDA-approved blood collection device that is positioned on the surface of an athlete’s upper arm or other limb. With the push of a button, the blood sample is collected from the surface of the skin and securely stored within the device. The collection process typically takes less than five minutes and can be completed by your DCO.

Honestly, my first reaction when reading this was "SURPRISE TEST!" Though, I guess if the collection process takes up to five minutes the athlete might notice.
And there might also be rules against testing people without their knowledge, though, when you become a professional athlete you kinda agree that you will accept being tested.
 
Re:

Tap Blood Collection System

...30 microneedles that are 350 microns in width and 1 mm long....

350 microns puts it somewhere between a 28 and 29 gauge hypodermic needle in diameter. The 31-gauge needle commonly used by diabetics for insulin injections is thinner still by about a fourth, so one wonders how these qualify as "microneedles." However, the typical insulin needle is quite longer, 8mm.

According to one article I found, the TAP device already has been approved by the USA Food and Drug Admin for HbA1c blood sugar testing.


The pivotal question, from my perspective, is how immune is it to adulterants, masking agents and other contaminants when applied to the skin (deliberately or otherwise). We know for instance that cyclists were thwarting some urine testing for PEDs by secreting a contaminant under their foreskin, which they dipped into the specimen as they were relieving themselves. Because I question the usefulness of a "new" test that the dopers already have devised a method to defeat.


RedheadDane said:
...Honestly, my first reaction when reading this was "SURPRISE TEST!" Though, I guess if the collection process takes up to five minutes the athlete might notice....
Much of the time probably is in documentation, establishing chain of custody, rather than the drawing of the sample.
 
Re: Re:

StyrbjornSterki said:
RedheadDane said:
Then why would they say that the collection process takes up to five minutes
Is not establishing chain of custody part of the process?

But it was mentioned under the explanation of how this particular testing method works. Surely establishing a chain of custody works the same way for every testing method.

But are you suggesting they actually should start performing surprise tests?
 
Aragon said:
fmk_RoI said:
Given that that's Shane Stokes, I wouldn't hold your breath waiting for a reliable source to be produced, that's likely to be no more than the usual stories about Nencini and Anquetil, with maybe knowledge of Merckx and Zoetemelk added to it.

The professional cycling team was top tier or local to Ekblom? If the former, would you be thinking Italy based
I don't know the team nor even the country, all I know is that when he discussed the matter in the media in 1971,...
According to one athlete who participated in the blood doping research in 1970 and who was regularly in contact with Björn Ekblom that time period, they were "a couple of French professional cyclists". The participant mentioned this in 2009 in an interview, but it isn't necessarily the only source on the matter.
 
Aragon said:
Aragon said:
fmk_RoI said:
Given that that's Shane Stokes, I wouldn't hold your breath waiting for a reliable source to be produced, that's likely to be no more than the usual stories about Nencini and Anquetil, with maybe knowledge of Merckx and Zoetemelk added to it.

The professional cycling team was top tier or local to Ekblom? If the former, would you be thinking Italy based
I don't know the team nor even the country, all I know is that when he discussed the matter in the media in 1971,...
According to one athlete who participated in the blood doping research in 1970 and who was regularly in contact with Björn Ekblom that time period, they were "a couple of French professional cyclists". The participant mentioned this in 2009 in an interview, but it isn't necessarily the only source on the matter.
Purely for sport, since speculation is pointless, but there would - IIRC - have been three main French teams in 71: Fagor/Mercer, Peugeot and Bic. I've love it have have been Bic and one of the riders to have been Jean-Marie Leblanc, cause, you know, that'd be poetry. (Bic did have Luis Ocaña, and Ocaña was alike to Anquetil in so many ways, on and off the bike, and Anquetil did play with his blood, even if it wasn't fully blood doping as we know it, and in later life, after retiring, Ocaña tried to recruit Pedro Celaya as Fagor's team doctor.) Peugeot, they of course, went on to work with François Bellocq, the expert at hormone rebalancing. And Fagor/Mercer at that time, they had Cyrille Guimard, a man who liked the cutting edge of science. As I say, purely sepeculation for sport, almost any team can be made to fit the frame.

Thanks for the update on this one.
 
It is also interesting that in 1976 the Le Monde journalist was quite convinced that blood doping was going on in the pro cycling when the issue wasn't discussed that much in the media.

If I shall have the opportunity, I will ask some information from the people themselves because I have been working on an essay/article series on the origins of blood doping that might see the light of the day in a few months in which I have incorporated some new material from Sweden sources.
 
Testing for selfie transfusions (autologous) using the age of blood cells as a marker:
A Duke University research team has found a way to help sporting officials detect whether an athlete's blood has been doped by an infusion of their own stored blood.
The science bit:
What Chi and his colleagues looked at in the red blood cells is nucleic acids, specifically RNA. Red blood cells were long thought to lack nucleic acids because they don't carry a nucleus, where one would normally find DNA. But it turns out they contain an abundant and diverse population of RNAs. Among these are some short RNA pieces called microRNAs (miRNA) which generally act to control the production of proteins in a cell.

The researchers drew three units of blood from volunteers and processed them to remove virtually all of the white blood cells and about 80 percent of the plasma, leaving behind a relatively purified sample of red blood cells, just as an autologous transfusion would require.

Then Jennifer Doss, a former Duke graduate student, and other lab members extracted and analyzed RNA samples taken from the cells at eight time intervals, from 1 day to 42 days. Changes in the RNA associated with storage became apparent as they compared the later samples to the Day 1 sample.
More

(H/T)
 
Re:

fmk_RoI said:
Testing for selfie transfusions (autologous) using the age of blood cells as a marker:
A Duke University research team has found a way to help sporting officials detect whether an athlete's blood has been doped by an infusion of their own stored blood.
The science bit:
What Chi and his colleagues looked at in the red blood cells is nucleic acids, specifically RNA. Red blood cells were long thought to lack nucleic acids because they don't carry a nucleus, where one would normally find DNA. But it turns out they contain an abundant and diverse population of RNAs. Among these are some short RNA pieces called microRNAs (miRNA) which generally act to control the production of proteins in a cell.

The researchers drew three units of blood from volunteers and processed them to remove virtually all of the white blood cells and about 80 percent of the plasma, leaving behind a relatively purified sample of red blood cells, just as an autologous transfusion would require.

Then Jennifer Doss, a former Duke graduate student, and other lab members extracted and analyzed RNA samples taken from the cells at eight time intervals, from 1 day to 42 days. Changes in the RNA associated with storage became apparent as they compared the later samples to the Day 1 sample.
More

(H/T)

I think the paper is open access, it's here:

https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.15605
 
fmk_RoI said:
After the many journalists who fell in love with Yannis Pitsiladis I find it hard not to be somewhat sceptical of these projects, especially at such an early stage and with so many hurdles to overcome. That said, if it comes good, it's interesting. Will definitely be keeping an eye out for further developments.
I'd be even slightly skeptical even if these researches would produce breakthroughs, because one problem with the blood doping research is always that even when they succeed in making the use of certain method more difficult, usually there is an alternative method available. While there could be less blood doping going on it isn't that certain if it is progress if certain participants can proceed with blood doping whereas others can't and if athletes are pushed to use very expensive and more hazardous methods.

Even if the blood doping methods would be eliminated one-by-one, there are always some undetectable methods, for instance no present or imaginable direct approach to autotransfusions can' detect direct infusion from an identical twin because there are no storage components in the blood nor blood deterioration, it is just identical red fluid flowing from person A to person B.

ABP program is an interesting approach because it at least seemingly makes it more difficult for everyone to blood dope despite all of its insensitivity issues etc. I think it is valid question how much focus there should be from the testers on what takes place within the Z-score limits and how much PED use should be allowed there. It could be that the present system is the best one even with its flaws, but I have started to have some doubts.

One fair but utopistic method to curtail blood doping use would be to take a suspicion index based on Hct, OFFscores and variations and for the UCI to add an extra brake into the bikes in order to slow down the cyclists with suspicious scores corresponding the level of suspiciousness. Even wih its flaws, a rare blood doper could go totally unpunished and if someone had high figures by a bad luck, his career wouldn't be ruined by a doping case.
 
Aragon said:
Even if the blood doping methods would be eliminated one-by-one, there are always some undetectable methods, for instance no present or imaginable direct approach to autotransfusions can' detect direct infusion from an identical twin because there are no storage components in the blood nor blood deterioration, it is just identical red fluid flowing from person A to person B.
Remember when it was said that certain teams were signing riders based on their blood type? Maybe the current 'vogue' for twins - Yates, Oliveira - will spark a new rumour if either of these two blood tests gets off the ground.
 

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