All You Wanted to Know About Sport Therapeutic Use Exemptions

Peter Russell

Disclosures

July 02, 2018

Starting in Noirmoutier-en-l’Île in the Vendée on July 7th, cycling's 2018 Tour de France will include 21 gruelling stages before the final day's sprint finish in Paris.

Chris Froome of Team Sky and Tom Dumoulin from Team Sunweb are expected to face-off in a rematch following the Giro d'Italia where they took first and second positions respectively.

The four-time Tour winner Froome's inclusion had been in doubt as he awaited the outcome of an adverse analytical finding (AAF) for the asthma drug salbutamol recorded after his victory in the Vuelta a España in September 2017.

However, cycling's governing body, the UCI, has now closed anti-doping proceedings against him.

In a statement, the UCI said it had "considered all the relevant evidence in detail (in consultation with its own experts and experts from WADA [the World Anti-Doping Agency]). On 28 June 2018, WADA informed the UCI that it would accept, based on the specific facts of the case, that Mr Froome’s sample results do not constitute an AAF. In light of WADA’s unparalleled access to information and authorship of the salbutamol regime, the UCI has decided, based on WADA’s position, to close the proceedings against Mr Froome".

Earlier this year, UK Anti-Doping (UKAD) acknowledged that Therapeutic Use Exemptions (TUEs) were a 'hot topic' but said it wanted to reinforce their value as a way for athletes to obtain approval for medications to treat legitimate medical conditions.

We asked Sam Pool, UKAD's medical programmes officer, to explain the TUE system.

Q&A

Medscape UK: What is the purpose of Therapeutic Use Exemption certificates?

Sam Pool: Athletes, like any general member of the population, may develop medical conditions which require the use of medications that appear on the Word Anti-Doping Agency (WADA) prohibited list. A Therapeutic Use Exemption, or a TUE, is a process by which an athlete with a well-documented and legitimate medical condition can be provided with an exemption to use such a medication or method.

It's important to note that it's not an open-ended licence. Each TUE is granted for a specific dose, frequency, route of administration and duration. Those criteria are outlined to the athlete on a TUE certificate, which is provided to them. If an athlete does not comply with those criteria, their TUE is no longer valid and they would be at risk of incurring an anti-doping rule violation.

Medscape UK: How can an athlete know whether the medication they are using needs to be covered by a TUE?

Sam Pool: Typically an athlete would submit an application form providing personal information [and] details of their proposed treatment plan. That application form is signed by themselves and their doctor. Importantly, they are also required to submit a portfolio of supportive medical evidence which confirms their requirement to use the prohibited medication or method.

That application form and supportive medical evidence is then sent to a TUE committee of doctors who review the supportive medical evidence against certain criteria, which have been set out by WADA within the international standards of TUEs.

There are four main criteria that need to be met in order for a TUE to be granted:

  • There would need to be a significant impairment to the athlete's health if the prohibited treatment was to be withheld.

  • The treatment is unlikely to provide any additional performance enhancement to the athlete other than returning them to their normal state of health.

  • There are no reasonable alternative therapeutic alternatives available to the athlete, or if there are they have been trialled and have proved to be ineffective.

  • The necessity of the use of that prohibited medication or method is not due to any prior use of prohibited substances without any valid exemptions.

Medscape UK: Are there particular medical conditions that athletes need to be aware of where medication will require a TUE?

Sam Pool: We advise athletes in the UK to use the website Global Drug Reference Online, or Global DRO for short; and that website's there for them to check the anti-doping status of any licenced medications, both prescription and over-the-counter medications available in the UK.

We're regularly updating the pharmaceutical data available on Global DRO with any new brands or formulation changes and we have a team of pharmacists here who review each entry. There's a three-level approval process before any entry makes it on to the live site, so any athlete can really be confident in the accuracy of the information provided.

It's a very popular resource. We received last year 350,000 searches on the UK site alone, and in total across the whole website, including the other countries, there was one million searches.

Medscape UK: What was behind the controversy in cycling last year over asthma and dosages of the medication, salbutamol?

Sam Pool: We don't speak about any individual cases.

Typically there are two types of substances within asthma inhalers, the first of which are beta-2 agonists, including salbutamol. The second is glucocorticosteroids. Short-acting beta-2 agonists, including salbutamol, are prohibited under S3 of the WADA prohibited list, and that particular medication is there to provide quick relief to asthma symptoms, and can also be used prior to exercise in order to prevent exercise-induced broncho-constriction.

However, there are circumstances where there is a permitted threshold of use. So, for inhaled salbutamol, that is permitted up to a maximum of 800 micrograms within a 12-hour window.

There is also a permitted threshold of use for the long-acting beta-2 agonists, which are typically combined with an inhaled corticosteroid. Formoterol is a long-acting beta-2 agonist which is often [found] in preventative inhalers. The permitted threshold of use for that particular substance is a maximum of 54 micrograms within a 24-hour window. And then salmeterol is the other substance, which has a permitted threshold of use under the WADA prohibited list [of] 200 micrograms inhaled over 24 hours.

Those permitted thresholds …acknowledge that those particular beta-2 agonists are not considered to be performance-enhancing when inhaled in those therapeutic doses. So, an athlete is not required to apply for a TUE if their use of inhaled salbutamol is less than 800 micrograms within a 12-hour window or within the two other permitted thresholds.

However, beta-2 agonists as a group of substances appear on the WADA prohibited list, as research has shown that they can have performance-enhancing effects through their anabolic properties – that is muscle-building and promoting muscular strength when they're administered orally rather than inhaled. So, within the WADA prohibited list there is a urinary threshold for both salbutamol and formoterol to aid distinguishing between oral and inhaled use.

For instance, the presence of salbutamol within the urine in excess of 1,000 nanograms per millilitre is deemed not to be consistent with the therapeutic use of that substance.

Medscape UK: There have been claims of TUEs being abused in sport. To what extent can we be confident of the system?

Sam Pool: At UKAD we have a number of controls in place to make it as difficult as possible for athletes to misuse the TUE system. Our TUE committee is formed of 11 doctors with a wide range of medical expertise, including fields such as endocrinology, rheumatology and psychiatry, and most also have experience working in sport and treating athletes.
 

In each application, three doctors out of those 11 are selected to form a review panel, including a relevant specialist where it's required. And then that panel must be unanimous in their decision to approve an application if it is to be granted. They all must be confident that the WADA criteria have been sufficiently met.

Further on from that, we can also grant conditions of approval within a TUE where we may request that the athlete provides further medical updates during their exemption, which continues to provide reassurance that they do require that prohibited substance to treat a legitimate medical condition.

Another control that we have in place here is we have a dedicated medical programmes officer such as myself, and I'm here to monitor the consistency within our TUE committee decisions and monitor trends of TUE applications that we've received from athletes, and then we can implement policies in response to those trends.

Over the last few years we have also created an independent TUE review panel, which meets on an annual basis to scrutinise the performance of our TUE programme through reviewing a sample of our TUE applications and the decisions made on them.

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