The need for therapeutic use exemptions (TUEs) or the permitted use of Prohibited Substances and Prohibited Methods by athletes to treat significant medical conditions arose when several classes of drugs used commonly in medicine were prohibited in sport by the International Olympic Committee (IOC) during the 1980s. However, although the IOC Medical Commission (IOC-MC) gave qualified support for the concept to formally start at the 1992 Barcelona Olympics, the Commission's fears that athletes might abuse the mechanism resulted in minimal publicity and its non-inclusion in the Medical Code of the Olympic Movement for 8 years. TUEs would not be widely publicised until the advent of the World Anti-Doping Agency which not only approved the principles of TUEs as developed by the IOC's Medications Advisory Committee (MAC) in 1991, but also introduced the name of TUE. Several changes to the Prohibited List have resulted in TUEs being necessary for substances that were permitted 20 years ago as disclosed in a review of TUEs approved at the 11 Olympic Games that the IOC's MAC, later the TUE Committee (TUEC), has operated. The IOC and its TUEC played a pivotal role in developing the concept of TUE which is now globally accepted.
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That Olympic athletes, indeed all athletes with documented and significant medical conditions, may seek and be approved to administer a Prohibited Substance or a Prohibited Method and train for and compete in sports is now widely acknowledged and accepted. This is termed a Therapeutic Use Exemption (TUE), although some were granted to Olympic and non-Olympic athletes before this name was introduced in 2001. The International Olympic Committee (IOC), through its Medical Commission (IOC-MC), had a pivotal role in the development of TUE and its TUE Committee (TUEC) has functioned since prior to the 1992 Olympic Games in Barcelona. London 2012 was the 11th Olympic Games at which it had operated. But in its early years, acceptance of the concept of TUEs had many difficulties. This paper will examine the origin and history of TUEs, including the problems encountered in achieving recognition, a review of the changing nature of TUEs approved at the Olympic Games and the current and future status with lessons learnt from London 2012.
History of TUE
When the IOC undertook the first extensive doping controls (>2000) at the 1972 Munich Olympics, the only drugs that were prohibited were stimulants and narcotics. Androgenic-anabolic steroids (AAS) were prohibited prior to the 1976 Olympics, although endogenous steroids such as testosterone could not be identified. During this period, there was no discussion about athletes needing a TUE. However, after diuretics, β-blockers and systemic glucocorticosteroids (GCS) were added to the IOC's Prohibited List1 in the 1980s, significant interference occurred in the availability of essential medications to manage medical conditions in elite athletes. Around 1987–1988, two male athletes without testes, one in Sweden and the other in Australia, sought to continue their testosterone replacement therapy and participate in their sport. Both were granted national approval.2 At the 1988 Calgary Games, an ice hockey player was approved to take oral GCS for inflammatory bowel disease (IBD) and later that year in Seoul, a rower with nephrotic syndrome was approved to continue her diuretic therapy and participate.2 Both were ad hoc decisions taken by all members of the IOC-MC, some of whom were not medically qualified.
In February 1991, the author presented a paper ‘Permission for athletes to use drugs contained in the IOC List of Banned Classes’ to the IOC-MC. This detailed the following criteria that should be met to approve any such application by an Olympic athlete:
The athlete would experience significant impairment of health if the prohibited medication was withheld;
No enhancement of performance could result from the administration of the prohibited substance as medically prescribed;
The person would not be denied the prohibited substance if he/she was not a competing athlete;
No available permitted or practical alternative can be substituted for the prohibited substance;
Retrospective approval would not be granted.
Independently, and at the same IOC-MC meeting, Professor Manfred Donike presented a paper on ‘Replacement therapy’ which focused on testosterone in anorchia. An interim Medications Advisory Committee (MAC) was appointed (D Catlin, A Ljungqvist and K Fitch, Convenor) and requested to develop guidelines to implement the proposal. This was undertaken and included
The complete medical details including the history, clinical findings and investigation must be submitted.
The necessity to administer the prohibited medication including the dosage, route and frequency of administration must be certified by a suitably qualified medical specialist.
The medical necessity to administer the prohibited substance cannot be the result, wholly or partially, of prior use of a drug from the banned classes or banned methods.
Additional investigations requested by the MAC will be undertaken at the athlete's or his/her National Olympic Committee's (NOC) expense.
Any doctor who provides the MAC with false information will be ineligible to be accredited as an Olympic team doctor or official.
Under no circumstances will permission be given to use any synthetic anabolic steroid.
However, the concept had its doubters and it would be another year before the IOC-MC agreed to allow the MAC to start operating prior to the Barcelona Games. However, the IOC-MC Chairman, supported by some Commission members, would not permit any publicity for ‘fear of abuse of the system’. Hence, only two applications were received for Barcelona 1992. Both were for oral GCS for well-documented IBD and were approved. Each athlete won a medal, although neither was in an individual event.
During these early years, MAC members were conscious that they were embarking on a new and potentially controversial undertaking and that their decisions must be able to withstand the closest scrutiny. In the mid-1990s, the MAC compiled the first document that established some circumstances in which certain prohibited substances and methods might be approved to manage specific medical conditions encountered in athletes. A number of conditions and circumstances for which permission would not be granted were also documented. The classes of prohibited drugs under consideration were diuretics, corticosteroids, β-blockers and AAS (only testosterone). No exemptions were contemplated for stimulants or narcotics.
In 1994, two world-class sailors applied to continue to administer testosterone at the 1996 Olympic Games if selected. Both had anorchia, one a congenital condition and the other surgical due to bilateral malignancies. Having considered these applications, the MAC sought the advice of independent expert endocrinologists who were ‘blinded’ as to the identity of each athlete, his NOC and his medical advisors. Both were approved and although neither athlete qualified at the 1996 Olympic yachting trials, one did compete in Athens 2004.
One unusual request was for erythropoietin in a Winter Olympic athlete prior to the 1994 Lillehammer Games because she had recently been a bone marrow donor for her brother with aplastic anaemia. It was the usual policy of the oncology centre concerned to withdraw and store a unit of blood prior to harvesting bone marrow and reinfusing this postharvest. (This would have been a Prohibited Method.) Owing to not wanting to interrupt her Olympic training programme and the urgency of her brother's need for a bone marrow donation, this was not undertaken and her haemoglobin fell by 2 g/dl. However, despite the compelling circumstances, the application was rejected.
Some early requests included an archer with 21-hydroxylase deficiency (salt losing) congenital adrenal hyperplasia (CAH) seeking oral GCS, which was approved. However, shortly after this, a shooter with 17-hydroxylase deficiency CAH who had been granted national approval was denied permission by her International Federation (IF) to administer GCS and compete internationally. Fortunately, intervention by the MAC reversed this decision and later, she competed successfully at the 2000 Olympic Games. Prior to Atlanta 1996, a female soccer footballer with C1-esterase deficiency hereditary angioneurotic oedema was approved to use danazol daily and participated. In contrast, an aging canoeist who had been prescribed testosterone for alleged hypogonadism and had the backing of his national antidoping agency sought permission to continue this therapy at Atlanta. The MAC advised that this athlete did not have a valid justification and rejected the application.
A well-publicised case that regrettably reflected that the MAC was compelled to remain ‘clandestine’ was that of an elite 22-year-old 3 m diver whose severe narcolepsy was diagnosed in January 1996. Immediately, she sought permission from her NOC and then from FINA to take stimulant medication but was rejected by both bodies. She continued to compete nationally and internationally and won national titles but seemingly was not required to take a doping control until a Grand Prix event in May 1999 when she admitted the use of dexamphetamine on the doping control form and tested positive. Despite being advised that her narcolepsy was so severe that she was at major risk of falling asleep on the 3 m diving platform and thus of potential injury, FINA's Doping Control Panel imposed a 12 month suspension. Intervention by the FINA Medical Commission resulted in the sanction being reduced to 6 months, but on appeal to CAS, this was further reduced to 2 months. Ironically, less than a month after her positive test, FINA modified their doping regulations to permit the use of a prohibited medication in special circumstances. The opinion of the MAC was not sought until shortly prior to her initial FINA hearing and then at the request of her NOC. The MAC had no hesitation in advising that she was entitled to a TUE. This may or may not have influenced both the FINA Medical Commission and the CAS. Had the IOC informed the stakeholders of the MAC's existence, this diver would have applied and been approved to take her medication in 1996. Soon after this decision by the MAC, an application was received from a track and field athlete from the same NOC whose narcolepsy had been proven conclusively by sleep studies. On this occasion, the opinion of an independent expert in sleep medicine was sought. This request was granted by the MAC for the recently released but prohibited modafinil—a wakefulness drug.
Between 1992 and 2003, the IOC's MAC (later TUEC) received numerous applications and its recommendations were believed to have been accepted on all occasions. In addition to functioning at the Olympic Games without publicity, the MAC provided advice to as many as 15 IFs and 11 NOCs who sought assistance. Few applications were received that could be deemed to be ‘opportunistic’, but one from a 33-year-old elite female weightlifter appeared to be. On the advice of a ‘Longevity Institute’ doctor, she sought permission to administer transdermal testosterone following her hysterectomy and bilateral oophorectomies performed for endometriosis. This was in addition to her replacement permitted hormone therapy. The application was rejected because no woman should ever be granted approval to take any AAS except danazol for very strict criteria. From its early days, the MAC decided that no AAS, except testosterone, could be approved for any male athlete and only then with a conclusive diagnosis and if the necessity was confirmed by an independent expert. This policy remains today.
In late 1998, approval for oral GCS treatment was granted to a young athlete in the sport of curling who had a successful renal transplant. Earlier that year, he had competed at the 1998 Nagano Olympics with an MAC-approved TUE for furosemide to assist in managing his chronic renal failure. At that time, a condition of approval was that the specific gravity of urine collected in doping control must be 1005 or greater by refractometer. However, improved analytical hardware has made this requirement no longer necessary.
A 56-year-old elite international shooter with a history of coronary artery bypass surgery was denied permission to take a cardioselective β-blocker and compete. Although his medical indication was not questioned, β-blockers had been demonstrated to produce a 13% improvement in shooting performance3 and this was deemed to contravene the criterion of ‘not enhancing sports performance’. Currently, the status of β-blockers in shooting remains unchanged, that is, TUEs should not be approved. Prior to Salt Lake City 2002, a bobsledder with low-serum testosterone after a unilateral radical orchiectomy for seminoma was denied permission to administer depotestosterone because of the presence of one intact testicle.
Recognising the concept of TUEs
However, problems persisted because the IOC had not provided NOCs and IFs with adequate information concerning therapeutic use. Many NOCs and IFs did not accept the policy of therapeutic use, first because it was not in the Medical Code of the Olympic Movement, and second, because of ignorance on the part of many sports authorities as to the concepts of therapeutic use. Thus, recognition of the concept of TUE continued to be difficult.
In 1998, the IOC's Juridical (Legal) Committee was incredulous at being advised by the author that TUEs had been approved for 6 years and criticised the IOC-MC Chairman for denying the MAC and its operation any publicity. But it would be another 2 years before the Juridical Committee would finally permit a one sentence mention of the concept as an addendum to the 2000 edition of the Medical Code of the Olympic Movement. This permitted a small breakthrough when the Anti-Doping policy for the Sydney 2000 Olympics made mention of the principle.2
Australia is believed to be the first country to have a committee with legislative authority to approve TUEs from August 1999. During the Sydney 2000 Olympic Games, Australia's TUEC organised a meeting of NOCs, IFs and interested persons which recommended that templates of established and proposed criteria for specific TUEs be prepared. This task was undertaken by Australia's TUEC and the templates circulated to attendees for feedback in 2001.
But it was the World Anti-Doping Agency (WADA), not the IOC, that provided global recognition and acceptance of TUE. Strenuous attempts to ‘sell’ the idea of TUE occurred at the 1999 World Conference on Doping in Sport in Lausanne from which WADA had its origins. Fortunately, two members of the MAC had significant WADA roles from its start and were able to ensure that the principle of TUE was accepted in the World Anti-Doping Code. An International Standard of TUE (ISTUE)4 was prepared between 2001 and 2003 and became operative when WADA finally assumed global responsibility for doping in January 2004. Significantly, the TUE criteria and guidelines developed by the MAC in 1991–1992 were incorporated virtually unaltered in the initial ISTUE.
WADA established a TUE Expert Group in 2004 and members reviewed the Australian TUE templates that had been updated at least annually. These were offered to WADA in 2005 but the offer was rejected. During the last 6 years, WADA has developed advice termed ‘Medical Information for TUE Committees’,5 which had a rocky start, but by involving experts in each field, it has become a valuable reference document for TUECs.
Recent Olympic Games
It is difficult to compare TUEs at Olympic Games as changes to the Prohibited List have necessitated TUEs for different substances and methods. Insulin was prohibited prior to Sydney 2000 and 5/8 TUEs approved were for insulin-dependent diabetes mellitus (IDDM). But the number of applications increased significantly after WADA assumed global responsibility for doping from the IOC. At the Games in Athens 2004, 24 TUEs for athletes from 19 NOCs and 15 sports were approved with 9/24 (38%) being for insulin. An appeal against a rejected application for systemic GCS was heard by WADA and the verdict confirmed that the IOC's MAC, now termed TUEC, had acted correctly. Intravenous infusions were prohibited prior to Torino 2006, although no athlete sought a TUE and 2/4 approved TUEs were for insulin for IDDM. Two applications were considered not to meet the criteria for approval and were discussed with each athlete's Chief Medical Officer (CMO) who accepted the TUEC's rationale and both were withdrawn. In Beijing, the TUEC recognised or approved 39 TUEs, of which nine were for IDDM. These 39 athletes were from 19 NOCs and 19 sports. For the first time, five intravenous infusions were approved. Interestingly, there were two Olympic athletes with well-documented Addison's disease approved for oral GCS. One application for stimulant medication for adult onset attention deficit hyperactive disorder was approved and a second withdrawn when a second opinion was sought, which was IOC's policy and later WADA's.
Between 2002 and 2008, inhaled β2 agonists (IBA) were managed by an IOC Independent Asthma Panel6 but not considered to be a TUE. However, in 2009, when WADA included IBAs in the prohibited list, the requirements to approve IBA use were identical to those of the IOC's Asthma Panel. This decision was partially rescinded just prior to Vancouver 2010 but two IBAs remained prohibited, formoterol and terbutaline. These accounted for 94 of the large number of 107 TUEs approved or recognised by the IOC's TUEC at Vancouver. Of the remaining 13, there were three approvals for insulin for IDDM, two for ADHD and one for an IF infusion. One IF-approved TUE for a female athlete to take dehydroepiandrosterone was a fundamental error since no female athlete should ever be approved to take any AAS except danazol. An appeal to WADA was successful, but WADA rules permitted the athlete 14 days to cease taking this prohibited medication, which allowed her to continue until after the Games. This is unsatisfactory and should be changed.
A number of difficulties were encountered at the recently successful London Olympic Games. From 2004, the IOC's TUEC had agreed to recognise TUEs for participating Olympic athletes approved by both IF and NADO TUECs after being subjected to close scrutiny. For Vancouver, the IOC was required to use WADA's Anti-Doping Administration and Management System (ADAMS).7 This posed a number of problems which were augmented in London with almost four times the number of participating athletes and IFs. First, the IOC TUEC's access to ADAMS was restricted since members were denied the opportunity to open uploaded medical files to allow them to confirm that an approved TUE had been granted according to established criteria. Second, more than half of the participating 205 NOCs do not upload TUEs onto ADAMS. Third, few NOCs heeded the request to provide the IOC's TUEC with a list of valid TUEs for their athletes. Finally, much time was spent in fruitlessly examining ADAMS to identify athletes believed to be accredited for London 2012 who may have had current a TUE. Almost all TUEs identified on ADAMS for athletes presumed to be competing in London were either for substances that were currently not prohibited (mainly IBA) or short-term TUEs that were no longer necessary or valid. Clearly, the IOC needs WADA to provide superior access and a more efficient way of ascertaining valid TUEs if ADAMS is to be used at future Olympic Games.
Prior to the opening of the London Olympic Village, CMOs were requested to provide the IOC's TUEC with details of all valid TUEs for their NOC athletes who would participate at the Games. Only two complied totally and 21 of the 31 preapproved TUEs that were recognised were from these two NOCs. During the Games, two athletes tested positive for prohibited substances and when advised, the NOCs of both athletes confirmed that each had a valid TUE that had not been disclosed. Hence, one must question how many other athletes had TUEs and did not advise the IOC. Although at each Games between 2002 and 2010, between 1/1000 and 1/1500 athletes were known to have IDDM, in London, only three athletes were reported to have a TUE for insulin (1/3500) which begs the question: were there more insulin-dependent diabetic athletes about whom the IOC was never advised? In London, the TUEC approved another 26 TUEs, with as customary most (15) being for systemic GCS and there were six intravenous infusions. One application was considered inappropriate and the CMO was contacted and the reasons provided. The NOC agreed to withdraw the application, institute an alternative permitted treatment and this athlete won a gold medal.
In summary, two decades of experience of TUEs at the Olympic Games have demonstrated that from a semiclandestine procedure in 1992, it has evolved so that currently there are established principles, a robust mechanism to apply and approve or reject applications, globally recognised medical indications and a mutual recognition of appropriately approved TUEs, at least at the Olympic Games. It is gratifying that the IOC's 1991–1992 pioneering criteria and guidelines have undergone only minor modifications to those of WADA that operated at London 2012. However, despite widespread understanding of the TUE principles and processes, it is essential to continue to strive for superior knowledge of the topic, better qualified and more experienced TUECs and hopefully a mutual recognition of correctly approved TUEs from experienced TUECs.
The author wishes to gratefully acknowledge the expertise and excellent assistance of his IOC MAC and TUEC colleagues Don Catlin (1991–2012), Arne Ljungqvist (1991–2003) and IOC TUEC colleagues, Margo Mountjoy (2004–2012), Patricia Sangenis (2004–2006) and Mark Aubry (2012). The author would like to acknowledge that some information has been obtained from the IOC-MC meeting minutes 1988–2003.
Funding The paper was self-funded. No funding from any source was sought or received.
Provenance and peer review Commissioned; internally peer reviewed.
Competing interests None.
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