Do dried blood spots have the potential to support result management processes in routine sports drug testing?-Part 2: Proactive sampling for follow-up investigations concerning atypical or adverse analytical findings / Mario Thevis, Tiia Kuuranne, Andreas Thomas, Hans Geyer. - ( Drug Testing and Analysis 13 (2021) 3 (March); p. 505-509)

• PMID: 33538088
• DOI: 10.1002/dta.3011

Abstract

Capillary blood sampled as dried blood spot (DBS) has shown substantial potential as test matrix in sports drug testing in various different settings, enabling the analysis of numerous different drugs and/or their respective metabolites. In addition to established beneficial aspects of DBS specimens in general (such as the minimally invasive and non-intrusive nature, and simplified sample transport), a yet unexplored advantage of DBS in the anti-doping context could be the opportunity of preserving a source of information complementary to routine doping controls performed in urine or venous blood. Whenever follow-up investigations are warranted or required, frequently collected and stored (but yet not analyzed) DBS samples could be target-tested for the compound(s) in question, in order to contribute to results management and decision-making processes.

Keywords: adverse analytical finding; atypical finding; doping; dried blood spot; sport.

In July 2018, UK Anti-Doping (UKAD) was informed that the UK Border Forced had intercepted and seized a package addressed to the rugby player Ralph Rainbow and contained Human Growth Hormone. In January 2020 in an interview with UKAD the Athlete admitted the purchase of this substance.

Hereafter in September 2018 the Rugby Football Union (RFU) reported 2 anti-doping rule violations against the Athlete for Possession (by purchase) and Use or Attempted Use of the prohibited substance Human Growth Hormone.

After notification a provisional suspension was ordered. Because the Athlete indicated that he did not wish to contest the charges the National Anti-Doping Panel renders a Decision based on the written submissions of the Parties.

The RFU contends that the Athlete had admitted the violations and had not disputed the charges. There was no evidence that the violation was not intentional nor were there grounds for a reduced sanction.

The Panel finds that the Athlete has committed the anti-doping rule violations and as he has not disputed the charges, he is deemded to have admitted the violations and to have waived his right for a hearing.

Therefore the National Anti-Doping Panel decides on 11 February 2021 to impose a 4 year period of ineligibility on the Athlete starting on the date of the provisional suspension, i.e. 30 September 2020.

The pharmaceuticalisation of 'healthy' ageing : Testosterone enhancement for longevity / Matthew Dunn, Kyle J.D. Mulrooney, Cynthia Forlini, Katinka van de Ven, Mair Underwood

• International Journal of Drug Policy (2021) 103159 (12 February)
• PMID: 33583680
• DOI: 10.1016/j.drugpo.2021.103159

Abstract

The United Nations estimates that the world's population will reach 8.5 billion by 2030, and the populations of most countries are expected to grow older. This is case for many developed countries, including Australia, the United Kingdom, Canada, the United States of America, and member states of the European Union. Older cohorts will comprise a larger proportion of overall populations, driven in part by our increases in life expectancy. An ageing population poses challenges for governments; notably, older people tend to have multiple, chronic health conditions which can place a burden of health budgets. At the same time, we are witnessing a shift in how we respond to the health needs of our populations, with global drug policy acknowledging that some substances are contributing to increased morbidity and mortality (e.g. opioids) while others may have beneficial therapeutic effects (e.g. psylocibin, cannabis). There is general agreement that as men age their levels of testosterone decrease, and there is some evidence to suggest that there have been population-level declines in testosterone which are not associated with age. Anecdotally, testosterone is accessed by men seeking to self-medicate in the belief that they are experiencing low testosterone levels. There has also been a rise in anti-ageing clinics in the United States, providing access to testosterone replacement therapy (TRT). The non-medical use of testosterone can result in a number of adverse health events, including complications from the use of black market or underground products. Placing testosterone under a new prescribing regime may address some of these concerns, but is society ready for this change, and if so, what would this regime look like? This paper will explore the issue of how society responds to enhancement for longevity, or how we increasingly use pharmaceuticals to address and prevent illness, with a specific focus on testosterone and testosterone deficiency.

In June 2020 the Athletics Integrity Unit (AIU) of World Athletics has reported 2 anti-doping rule violations against the Kenyan Athlete Nicholas Kiptoo Kosgei after his samples, provided in December 2019 and in February 2020, tested positive for the prohibited substance Prednisone.

After notification the Athlete gave a prompt admission, waived his right for a hearing, accepted a provisional suspension and the sanction proposed by the AIU.

The Athlete explained that he had used prescribed Prednisone tablets as treatment for his medical condition and also self medicated Prednisone in February 2020. The Athlete acknowledged that he didn't mention to his doctor that he was an athlete, failed to check his medication before using, nor made an application for a TUE.

The AIU finds that the two reported anti-doping rule violation are considered as one single violation. The AIU accepts that the violation was not intentional and that the Athlete established ground for No Significant Fault or Negligence.

The AIU holds that the Athlete bears a low middle degree level of Fault considering that he is a relative young elite level athlete, not very experienced in anti-doping with lack of anti-doping education.

Therefore the AIU decides on 12 February 2021 to impose a 16 month period of ineligibility on the Athlete starting on the date of the second sample collection, i.e. on 2 February 2020.

Co-creating a social science research agenda for clean sport : An international Delphi study / Ian D. Boardley, Martin Chandler, Susan H. Backhouse, Andrea Petróczi

• International Journal of Drug Policy 92 (June 2021), 103161
• PMID: 33589380
• DOI: 10.1016/j.drugpo.2021.103161

Abstract

Background: Doping in sport is a significant issue. To date, research informing doping prevention has lacked a framework guiding research priorities. To ensure research is coordinated, sustainable and focused on end-user priorities, this study co-created the first research agenda for doping prevention.

Methods: The Delphi method was used to develop this agenda. Based upon two substantive reviews of the doping literature and 12 focus groups across five countries, a questionnaire was developed assessing the importance of 15 research topics and identifying research questions. Eighty-two anti-doping stakeholders with relevant expertise were invited to be panel members. In Round 1, an expert panel (n = 57; 70% response rate) completed this questionnaire. In Round 2, panel members (n = 33; 58% response rate) ranked for relative importance the eight topic areas rated highest in Round 1, before doing the same for research questions within each topic. Based on these rankings, a draft agenda was created. In Round 3, panel members (n = 26; 79% response rate) rated the degree to which they accepted this agenda, the feasibility of its delivery and identified possible barriers and facilitators to implementation.

Results: The results of Round 1 and Round 2 were used to create a draft agenda consisting of 18 research questions stratified across eight topic areas. This agenda was either fully (n = 16) or mostly (n = 9) accepted by the panel in Round 3 (96.2%). Research topics included the effectiveness of interventions/education programmes, environmental influences, long-term development of protective and risk factors in athletes and their entourage, athletes' experiences of anti-doping procedures and athletes' place in the anti-doping system.

Conclusions: A rigorous exercise created an agenda for doping prevention research. Adoption and application of this agenda should lead to better coordination, more efficient use of funding, enhanced uptake of research findings and more effective doping prevention education.

Related cases:

• CAS 2019_A_6148 WADA vs Sun Yang & FINA - Annulled Award
  February 28, 2020
• CAS 2019_A_6148 WADA vs Sun Yang & FINA - Final Award
  June 22, 2021
• FINA 2019 FINA vs Sun Yang
  January 3, 2019
• Swiss Federal Court 4A_287_2019 Sun Yang vs WADA & FINA
  January 6, 2020
• Swiss Federal Court 4A_413_2019 Sun Yang vs WADA & FINA
  October 28, 2019

The Swiss Federal Supreme Court dismisses on 14 February 2021 the appeal filed by Chinese swimmer Sun Yang against the decision of the Court of Arbitration for Sport in Lausanne. The contested decision (CAS 2019/A/6148), which imposed a ban of four years and three months on Sun Yang from February 2020, does not violate fundamental principles of public order; nor was Sun Yang's right to be heard infringed. The Federal Supreme Court did not enter into the merits of the athlete's further objections.

In its decision of 28 February 2020, the Court of Arbitration for Sport (CAS) had imposed an eight-year ban on the Chinese swimmer Sun Yang for violating the doping rules of the International Swimming Federation ("FINA Doping Control Rules", 2017 edition). In December 2020, the Federal Supreme Court upheld Sun Yang's appeal and annulled the CAS decision on the grounds of bias on the part of one of the CAS arbitrators (Federal Supreme Court press release of 15 January 2021 ). On 22 June 2021, the CAS ruled again on the case in a new composition of the arbitration panel and imposed a ban of four years and three months from 28 February 2020 on Sun Yang.

The Federal Supreme Court dismissed Sun Yang's appeal against this decision insofar as it was admissible. Decisions of the CAS cannot be reviewed freely by the Federal Supreme Court. The Court's review of the merits is limited by law to the question of whether the contested CAS decision violates fundamental and widely recognised principles of public order ("ordre public"). The contested decision does not violate public policy. The Federal Supreme Court also rejected Sun Yang's claims that the CAS had violated his right to be heard. The Federal Supreme Court did not consider Sun Yang's objections regarding the timeliness of the appeal filed by the World Anti-Doping Agency (WADA) with the CAS in 2019. However, the athlete's objections in this regard would be unfounded in any case. Furthermore, the Federal Supreme Court did not consider the complaint that the Court's limited power of review in appeals against CAS decisions violated the right to an effective remedy within the meaning of Article 13 of the European Convention on Human Rights.

Evaluation of dermorphin metabolism using zebrafish water tank model and human liver microsomes / Juliana de L. Castro, Henrique M.G. Pereira, Valéria de Sousa, Maria Elvira P. Martucci. - (Current Drug Metabolism (2021) 15 February)

• PMID: 33593255
• DOI: 10.2174/1389200222666210216095753

Abstract

Background: Dermorphin is a heptapeptide with an analgesic potential higher than morphine that does not present the same risk for the development of tolerance. These pharmacological features make dermorphin a potential doping agent in competitive sports and is already prohibited for racehorses. For athletes, the development of an efficient strategy to monitor for its abuse necessitates an investigation of the metabolism of dermorphin in humans.

Methods: Here, human liver microsomes and zebrafish were utilized as model systems of human metabolism to evaluate the presence and kinetics of metabolites derived from dermorphin. Five hours after its administration, the presence of dermorphin metabolites could be detected in both models by liquid chromatography coupled to high resolution mass spectrometry.

Results: Although the two models showed common results, marked differences were also observed in relation to the formed metabolites. Six putative metabolites, based on their exact masses of m/z 479.1915, m/z 501.1733, m/z 495.1657, m/z 223.1073, m/z 180.1017 and m/z 457.2085, are proposed to represent the metabolic pattern of dermorphin. The major metabolite generated from the administration of dermorphin in both models was YAFG-OH (m/z 457.2085), which is the N-terminal tetrapeptide previously identified from studies with rats.

Conclusion: Its extensive characterization and commercial availability suggests that it could serve as a primary target analyte for the detection of dermorphin misuse. The metabolomics approach also allowed the assignment of other confirmatory metabolites.

Medicinal Use of Testosterone and Related Steroids Revisited /  Jan Tauchen, Michal Jurášek, Lukáš Huml, Silvie Rimpelová. - (Molecules 26 (2021) 4 (15 February); p. 1-20)

• PMID: 33672087
• PMCID: PMC7919692
• DOI: 10.3390/molecules26041032

Abstract

Testosterone derivatives and related compounds (such as anabolic-androgenic steroids-AAS) are frequently misused by athletes (both professional and amateur) wishing to promote muscle development and strength or to cover AAS misuse. Even though these agents are vastly regarded as abusive material, they have important pharmacological activities that cannot be easily replaced by other drugs and have therapeutic potential in a range of conditions (e.g., wasting syndromes, severe burns, muscle and bone injuries, anemia, hereditary angioedema). Testosterone and related steroids have been in some countries treated as controlled substances, which may affect the availability of these agents for patients who need them for therapeutic reasons in a given country. Although these agents are currently regarded as rather older generation drugs and their use may lead to serious side-effects, they still have medicinal value as androgenic, anabolic, and even anti-androgenic agents. This review summarizes and revisits the medicinal use of compounds based on the structure and biological activity of testosterone, with examples of specific compounds. Additionally, some of the newer androgenic-anabolic compounds are discussed such as selective androgen receptor modulators, the efficacy/adverse-effect profiles of which have not been sufficiently established and which may pose a greater risk than conventional androgenic-anabolic agents.

Mr Alexander Parking is the Executive Director for the Russian Athletics Federation (RusAF). 

In August 2018 the Athletics Integrity Unit (AIU) of the IAAF (now: World Athletics) has reported an anti-doping rule violation of Tampering against the high jumper Danil Lysenko after the AIU had opened an investigation against the Athlete regarding his Whereabouts Failures.

With the assistance of the Russian Anti-Doping Agency (RUSADA) the AIU discovered that the Athlete had forged medical documents to the AIU. The AIU also concluded that RusAF officials had been involved in the provision of false explanations and forged documents to the AIU in order to explain whereabouts failures by the Athlete. 

As a result in November 2019 the AIU issued charges against Mr Alexander Parkin, RusAF and several other RusAF officials for committing multiple anti-doping rule violations:

• Tampering or Attempted Tampering
• Complicity
• Refusal or failure to report an Anti-Doping Rule Violation
• Refusal or failure to cooperate with investigations.

After notification Mr Parkin admitted the violations, waived his right to be heard, accepted a provisional suspension and the sanction proposed by the AIU. The AIU considered the violations as a single violation and the sanction based on the anti-doping rule violation that carries the more severe sanction. 

Therefore the AIU decides on 16 February 2021 to impose a 4 year period of ineligibility on Mr Alexander Parker starting on the date of the notification, i.e. on 21 November 2019.

Related case:

World Athletics 2019 WA vs Elena Orlova (1)
August 21, 2020

Ms Elena Orlova is the Senior Coordinator for the Russian Athletics Federation (RusAF). 

In August 2018 the Athletics Integrity Unit (AIU) of World Athletics has reported an anti-doping rule violation of Tampering against the high jumper Danil Lysenko after the AIU had opened an investigation against the Athlete regarding his Whereabouts Failures. 

With the assistance of the Russian Anti-Doping Agency (RUSADA) the AIU discovered that the Athlete had forged medical documents to the AIU. It also concluded that RusAF officials had been involved in the provision of false explanations and forged documents to the AIU in order to explain whereabouts failures by the Athlete.  

As a result in November 2019 the AIU issued charges against Ms Elena Orlova, RusAF and several other RusAF officials for committing multiple anti-doping rule violations:

• Tampering or Attempted Tampering
• Complicity
• Refusal or failure to report an Anti-Doping Rule Violation
• Refusal or failure to cooperate with investigations.

On 21 August 2020, in seperate disciplinary proceedings, the World Athletics Disciplinary Tribunal had already decided to impose an 6 year period of ineligibility on Ms Orlova after the AIU had established that she had failed to provide digital evidence without compelling justification during their investigations. She also had disregarded to comply with the Order ussued by the Disciplinary Tribunal in July 2019. 

In the current case Ms Orlova failed to repond to the charges against her within the set deadline regarding the reported anti-doping rule violations. Therefore the AIU deems that Ms Orlova has admitted the anti-doping rule violations, waived her right for a hearing and accepted the sanction proposed by the AIU. The AIU further considered the violations as a single violation and the sanction based on the anti-doping rule violation that carries the more severe sanction. 

Therefore the AIU decides on 16 February 2021 to impose a 4 year period of ineligibility on Ms Elena Ikonnikova to be served concurrently with the already imposed 6 year period of ineligibility.