Piss take: Researchers defend study claiming Salbutamol urine test is flawed

by Suze Clemitson


“We lie as doctors. We say we make you better but actually we just make you as good as you were before you got ill. This fact means we rarely see a substance that makes someone better when they’re already very good at something.”

I’m talking to Adam Cohen of the Centre for Human Drug Research (CHDR), a modern light-filled glass cube in Leiden. Cohen is also the executive editor of the British Journal of Clinical Pharmacology where the strikingly titled research paper Futility of urine tests in Salbutamol doping was published this month. Unsurprisingly it’s been seized on as a bullet in the chamber of the Chris Froome defense.

Unless you’ve been living under a rock, it’s been impossible to escape the news that Froome has fallen foul of the WADA rules for using asthma drug Salbutamol, returning a sample that, even adjusted for dehydration at 1429ng/ml, remains significantly above the permitted threshold of 1000ng/ml. An atmosphere of controversy  accompanies his every appearance. Fellow riders like 2017 Giro d’Italia champion Tom Dumoulin claim Froome shouldn’t be competing at all.

But the rules state differently and, until the case is resolved, Froome is free to arrive at the start line of any race he chooses; sometimes, like on Monte Zoncolan on Saturday, he crosses the finish line first, too. He’s currently sitting fourth overall at the Giro d’Italia with three big mountain stages remaining, and may just stand on the final podium in Rome.

Simulations within the Leiden model showed a very large range of salbutamol concentrations, with a significant portion of virtual subjects (15.4%) exceeding the WADA threshold limit of 1000ng/mL at one hour post-dose. Their summary conclusion states: “The observed large variability in urine concentrations indicates that determining the administered dose from a single untimed urine sample is not feasible. The current threshold inadvertently leads to incorrect assumptions of violation, whereas many violations will go unnoticed, especially when samples are taken long after drug administration. These issues, combined with the dubious assertion of its anabolic effect, leads us to conclude that the large effort involved in testing should be reconsidered.”

Futile. Not feasible. Incorrect.

The study very clearly favors the defense of any athlete found to have tested over the permitted threshold for Salbutamol. So were Cohen and fellow researchers Jules Heuberger and Sven van Dijkman funded directly by Team Sky to challenge the integrity of the test? Cohen tells me the research was internally funded and that no one from Team Sky has contacted CHDR before or since its completion.

“We feel deeply about evidence-based control in drugs in sport,” he continues, his voice a resonant purr. “And we’re researchers who find ourselves in the fortunate position of doing what we want to do. We don’t see our role as working for sportsmen or lawyers, but because we have an academic job to do in a very traditional way.”

Once their research is in the public domain, Cohen says, the public — and that includes WADA and Team Sky — can do with it as they wish. “We never wrote to the press,” he says. “The paper was put out in peer-reviewed journals.”

The Leiden model presupposes that riders use the maximum allowable dose of 800mcg of Salbutamol, whereas Team Sky are on record stating that Froome must have been tested immediately after taking a  couple of metred puffs of his inhaler. Would it be fair to say that the results don’t speak to Froome’s defense at all?

“Of course it doesn’t speak to his defense,” Cohen says. “What we’re saying is that this kind of information — he took a couple of puffs at an undisclosed moment, collected urine with a non-disclosed amount of concentration at an undisclosed moment, and gave a certain concentration — has absolutely no relation to the drugs he used.”

Cohen says they could input his doses into their model, “but it wouldn’t reflect the precise situation he was in at that point.”

He insists that what he and his fellow CHDR researchers are addressing is the issue of a test that is pharmacologically flawed. “Does that mean Froome is outside the rules or not? We can’t tell and we don’t want to tell,” he adds emphatically. “What we’re saying is that our expertise — which is clinical, pharmacological expertise — is lacking in sports medicine.”

I asked South African sports scientist Ross Tucker for his take on the CHDR paper. Tucker identifies two issues with the model, which claims that the WADA Salbutamol test is not fit for purpose because it doesn’t detect genuine abuse, while returning upwards of 15% of false positives. (For clarity, a false positive is a sample that tests positive while actually being  drug free, while a false negative comes up clear although the athlete has in fact taken performance enhancing drugs.)

First, Tucker argues, if athletes are using the maximal doses of 800mcg as the model assumes — and bearing in mind the number of asthmatics in the professional peloton far outstrips the general population — where are all the false positives? 

“Then factor in dehydration that is known to increase the concentrations measured, and there’d be many false positives if the test is truly not fit for purpose.”

On the other hand, if riders are not using the maximal dose in one go, as seems to be the case in the Froome defense, does the model have any relevance to what’s actually happening in professional sport?

“Remember, they evaluated a scenario where the dice have been ‘loaded,’ in the sense that they’re testing what happens when an athlete takes the largest allowed dose all at once, does so twice a day, with the minimum allowed gap of 12 hours between doses, and then provides a urine sample within an hour of doing so” continues Tucker. “Then, under those circumstances, 15% fail a test. 

“But in pro sport, you hardly have any situations like this. That suggests that the model should have looked at a different set of behaviours. A few puffs, once every few days, maybe. Test what the athletes actually do, and then criticize an undesired outcome with validity. I think the outcome would be quite different then.”

Cohen and Heuberger refute any criticism that their research papers could be seen as undermining the global anti-doping effort.

“The reason doping exists is that people have an idea that certain drugs make them much better in sport. We challenge that concept. It’s not easy to be better at anything other than by practicing,” Cohen asserts.

It’s a bold statement and one that exposes the gulf between the academic mindset and Malcolm Gladwell’s outliers and the enduring and well-documented search for a performance edge, from the Pelissier brothers “dynamite to Willy Voet’s trunkful of EPO. It’s also a hypothesis that ignores the endless shades of grey that lie at the thorny, dirty heart of why riders dope — for the good of the team, to chase that last fat contract, the weight of history, the ease of gaming the system. It’s a hypothesis that ignores all the dreams and hopes and lies that can’t be modeled in a computer simulation.

Cohen argues that the information young riders receive is flawed because it doesn’t address the doubts surrounding the efficacy of so-called performance enhancing drugs, the hoodoo and old wives’ tales handed down from director to soigneur to rider throughout the history of the sport.

“They’re being told they’re not allowed to do it, which in a way is an incentive to do it,” Heuberger adds. “Our Salbutamol paper shows that the doping rules cannot protect athletes who play by the rules. We’re not undermining, we’re trying to show that the rules and the control mechanisms aren’t sufficient.”

Besides, Cohen tells me, “people think that beta agonists make you cycle fast and the evidence for that is quite limited. Test these things properly and you show sportsmen they have no value at all.”

It’s an interesting argument, and one that Tucker robustly refutes. “I’ve never met an athlete who wouldn’t try something, even if they know it’s unlikely to work. They wear the same socks for weeks, just because they believe it will help them.”

Heuberger, who was also involved in a controversial EPO study undertaken by the same group in 2017, goes further. “There’s no evidence that [PEDs] improve performance, definitely not for elite athletes.”

Cohen scoffs at the idea of there being a “secret place” where all that research has been done, and I wonder again how familiar the Leiden team are with the huge body of literature that relates to the work of performance enhancement in sport. The IOC-funded research undertaken by Francesco Conconi springs to mind.

“I’m a doctor,” Cohen concludes. “I treat patients, and one one of the things I’m personally quite convinced of is that making people better with medicine over their optimal physiological situation is virtually impossible.”

Yet a soigneur or team doctor rarely treats an athlete who is in  a state of wellness. By the end of a three week Grand Tour, argues Tucker, a rider is no longer “healthy” in the way most of us would understand, with depleted red blood cells and hormone disturbances. 

“A doctor who provides drugs to an athlete is treating ‘exercise-induced temporary unwellness,’ with very clear benefits to performance, Tucker tells me. “Elite competition or training causes physiological changes that we recognize most obviously as acute or chronic fatigue, or injury. These are reversible using banned medicines. Be they testosterone, growth hormone, EPO, other steroids, et cetera, if medicines can accelerate the body’s recovery from very hard, ‘damaging’ exercise, then they will improve performance capacity, and thus performance.”

If the model says that the only way to be better at sport is by practicing, Tucker argues, then performance-enhancing drugs are enabling riders to train harder. “And you can’t say now that they don’t work, even by the Leiden model.” 

So, all that said, will we see the Leiden team at the Court of Arbitration for Sport?

“Not likely,” Cohen says. “It’s in the public domain and people can do with it as they like. We’re not interested, and we’re not legal experts.”

Still, Cohen and his co-researchers stand by their peer-reviewed model. “What we’re saying is that it’s pharmacologically impossible to determine the dose of a drug from the urine concentration.”

It seems that Froome’s defense will remain a question for now, caught in the stasis between the pharmacological model and the reality of sports medicine.

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