In May 2019 the International Association of Athletics Federations (IAAF) has reported an anti-doping rule violation against the Iranian Athlete Hosein Keyahni after his sample tested positive for the prohibited substance Erythropoietin (EPO). After notification the Athlete admitted the violation, waived his right to be heard, accepted a provisional suspension and the sanction proposed by the IAAF. The Athlete denied the intentional use of the substance and explained that he had high altitude training and underwent medical treatment because he felt dizzy and had dyspnea and numbness. He demonstrated with medical evidence that his doctor administed prescribed EPO while he wasn’t aware that this was a prohibited substance. Therefore the IAAF Athletics Integrity Unit (AIU) decides on 20 June 2019 to impose a 4 year period of ineligibility on the Athlete starting on the date of the provisional suspension, i.e. on 21 May 2019.
A next-generation sequencing method for gene doping detection that distinguishes low levels of plasmid DNA against a background of genomic DNA
A next-generation sequencing method for gene doping detection that distinguishes low levels of plasmid DNA against a background of genomic DNA / Eddy N. de Boer, Petra E. van der Wouden, Lennart F. Johansson, Cleo C. van Diemen, Hidde J. Haisma. - (Gene Therapy (2019) 11 July; p. 1-9). - https://doi.org/10.1038/s41434-019-0091-6 _________________________________________________ Abstract Gene doping confers health risks for athletes and is a threat to fair competition in sports. Therefore the anti-doping community has given attention on its detection. Previously published polymerase chain reaction-based methodologies for gene doping detection are targeting exon–exon junctions in the intron-less transgene. However, because these junctions are known, it would be relatively easy to evade detection by tampering with the copyDNA sequences. We have developed a targeted nextgeneration sequencing based assay for the detection of all exon–exon junctions of the potential doping genes, EPO, IGF1, IGF2, GH1, and GH2, which is resistant to tampering. Using this assay, all exon–exon junctions of copyDNA of doping genes could be detected with a sensitivity of 1296 copyDNA copies in 1000 ng of genomic DNA. In addition, promotor regions and plasmid-derived sequences are readily detectable in our sequence data. While we show the reliability of our method for a selection of genes, expanding the panel to detect other genes would be straightforward. As we were able to detect plasmidderived sequences, we expect that genes with manipulated junctions, promotor regions, and plasmid or virus-derived sequences will also be readily detected.
Mr. Vitaly Mutko, was the current Deputy Prime Minister of Russia and was the Russian Minister of Sport, Tourism and Youth Policy from 12 May 2008 until 21 May 2012 and the Russian Minister of Sport from 21 May 2012 until 19 October 2016. Two reports commissioned by WADA, published by Prof. Richard McLaren as Independent Person (IP) on 18 July 2016 and 9 December 2016, showed detailed evidences of organised manipulation of some Russian samples collected during the Sochi 2014 Olympic Winter Games. The IP reports describe how urine bottles were opened and urine was switched with clean modified urine coming from a “biobank”, and how urine density had to be adjusted to match that recorded on the doping control form (if different at the time of collection) by adding salt to the sample. As a result of the McLaren Reports the IOC Oswald Commission started investigations in order to establish the possible liability of individual athletes and to issue any sanctions so that decisions could be taken as far in advance of the 2018 Winter Games as possible. At the same time the IOC Schmid Commission started their investigations to establish the facts on the basis of documented, independent and impartial evidence. On 2 December 2017, the Schmid Commission published its report, confirming the systemic manipulation of the anti-doping rules and system in Russia, which caused “exceptional damage to the integrity of the IOC, the Olympic Games and the entire Olympic movement”. The Schmid Commission concluded that members of the Ministry of Sport and its subordinated entities were directly involved in the manipulation; however, the Schmid Commission did not find sufficient documented, independent and impartial evidence to decide whether the Mr Mutko was personally involved in or had knowledge of that manipulation. Nevertheless, the Schmid Commission determined that the Mr Mutko, as the then head of the Ministry of Sport, had the “ultimate administrative responsibility for the acts perpetrated at the time within the Russian Ministry or the entities under its responsibility” and, accordingly, recommended that he bear “the major part” of that administrative responsibility. The Schmid Commission urged the IOC Executive Board (EB) to “take the appropriate measures that should be strong enough to effectively sanction the existence of a systemic manipulation of the anti-doping rules and system in Russia, as well as the legal responsibility of the various entities involved”. Consequently the IOC EB formally approved the Schmid Report on 5 December 2017 and decided: "[…] IV. To exclude the then Minister of Sport, Mr Vitaly Mutko, […] from any participation in all future Olympic Games”. The IOC never formally notified Mr Mutko of this Decision. The IOC only published this Decision, without any grounds, in the form of a press release in both English and Russian, on its official website under the category “News”. Hereafter in December 2017 Mr Mutko appealed the IOC EB decision of 5 December 2017 with the Court of Arbitration for Sport (CAS) and requested the Panel to set aside paragraph IV of the IOC EB Decision of 5 December 2017. Mr Mutko argued that the Appealed Decision must be set aside because it imposed a sanction on him without a proper legal basis. The IOC, on the other hand, seeked to uphold the Appealed Decision. The IOC maintained that the Appealed Decision did not impose a sanction; rather, it simply declared “in advance” the IOC’s intent to reject any future application for Mr Mutko’s participation in the Olympic Games. In the IOC’s view, such a declaration is markedly different from a decision imposing a sanction on an individual and has not affected the legal position and rights of Mr Mutko. Further, the IOC claimed that the Appealed Decision was based on a proper legal basis of the Olympic Charter. The Panel holds that the Appealed Decision set forth a sanction against Mr Mutko. Consequently, as for any challenged sanction, the Panel must verify whether the sanction was grounded on a proper legal basis. Here the Panel established that Mr Mutko was not and is not an Olympic competitor, a member of an Olympic delegation, a referee or member of a jury, and does not hold any Olympic accreditation which might be withdrawn. Finally, the Panel notes that the IOC has even admitted that, in the event the Panel characterized the Appealed Decision as a sanction (as it has done so) the Appealed Decision would have no legal basis due to the IOC’s lack of authority to issue any form of disciplinary sanction against Mr Mutko as an individual not subject to the IOC’s jurisdiction and regulations. In light of the foregoing, the Panel must set aside the Appealed Decision for lack of a legal basis. Therefore the Court of Arbitration for Sport decides on 3 July 2019 that: 1.) The appeal filed by Mr. Vitaly Mutko on 26 December 2017 is upheld. 2.) The decision concerning Mr. Vitaly Mutko, adopted by the Executive Board of the International Olympic Committee on 5 December 2017, is set aside. 3.) The costs of this arbitration, to be determined and served to the parties by the CAS Court Office, shall be equally borne by both parties. 4.) Each party shall bear his or its own legal fees and other expenses incurred in connection with this arbitration. 5.) All further or different motions or prayers for relief are dismissed.
In June 2019 the Canadian Centre for Ethics in Sport (CCES) has reported an anti-doping rule violation against the Athlete Amanda Chudoba Obrigewitch after her sample tested positive for the prohibited substances Hydrochlorothiazide without a valid TUE. After notification the Athlete gave a prompt admission, waived her right for a hearing, accepted the provisional suspension and the sanction proposed by CCES. The CCES established that the Athlete had a diagnosed condition and had a valid medical prescription for the use of Hydrochlorothiazide for therapeutic purposes as directed by her physician. Although the Athlete was subsequently granted a TUE for the use of Hydrochlorothiazide, as an Athlete in the National Athlete Pool the Athlete was required to have a TUE in advance – prior to using Hydrochlorothiazide in-competition. The CCES finds that the Athlete was careless in not filing her TUE application on time. The CCES holds that there is No Significant Fault or negligence in this case and considers the Athlete’s degree of fault to be low. Therefore the CCES decides on 3 July 2019 to impose a 1 month period of ineligibility on the Athlete starting on the date of the provisional suspension, i.e. on 21 June 2019. Under the Rules at least 50% of the sanction (2 weeks) must be served after 21 June 2019 as it ends on 5 July 2019.
Stakeholder Notice regarding meat contamination / World Anti-Doping Agency (WADA). - Montreal : WADA, 2019 _________________________________________________ On 16 May 2019, the World Anti-Doping Agency’s (WADA’s) Foundation Board decided to amend Article 7.4 of the World Anti-Doping Code (Code) to allow WADA-accredited Laboratories (Laboratories) to report Atypical Findings (ATFs) for the Prohibited Substance clenbuterol. Under the current version of Article 7.4 of the Code, Laboratories may only report analytical testing results for exogenous Prohibited Substances as Adverse Analytical Findings (AAFs) but not as ATFs, which does not allow for investigations to take place when potential meat contamination scenarios arise – as has been the case with clenbuterol. As such, if the current Code is strictly followed, Anti-Doping Organizations (ADOs) are required to assert an Anti-Doping Rule Violation (ADRV) against the athlete if the B sample results confirm the A sample findings (or the athlete waives the analysis of their B sample). The purpose of the amendment to Article 7.4 of the Code – which will come into force on 1 June 2019 and is an interim solution until the 2021 Code and the forthcoming International Standard for Results Management (ISRM) come into effect – is to provide ADOs with the possibility of conducting an investigation when low concentrations of identified Prohibited Substances that are known meat contaminants are detected by Laboratories and reported as ATFs. This will ensure that valid meat contamination cases are dealt with fairly and, notably, may prevent athletes from having their competition results disqualified as a result of eating contaminated meat. In order to provide guidance to ADOs faced with potential meat contamination cases, WADA has developed a Stakeholder Notice regarding Meat Contamination (Notice) that details the reporting instructions for Laboratories depending on the concentration of clenbuterol detected in an athlete’s sample and includes the investigative steps that ADOs must follow in such situations. After following the instructions and investigative steps indicated in the Notice, ADOs may close cases and allow an athlete to retain their results (for samples collected in-competition) if it is determined that the detection of clenbuterol in their sample is consistent with meat contamination. However, if, following the investigation, the reported ATF is not consistent with meat contamination, or if the concentration of clenbuterol exceeds the designated threshold, an ADRV will be asserted and the standard results management process will proceed. WADA hopes that the instructions found in the Notice and that the amendment to Article 7.4 of the Code will assist ADOs faced with potential clenbuterol meat contamination cases and will ensure that cases are managed fairly for all athletes. Please feel free to contact firstname.lastname@example.org should you have any questions or concerns.
iNADO Update (2019) 6 (21 June) Institute of National Anti-Doping Organisations (iNADO) ____________________________________________________ Contents: - WADA and iNADO to strengthen Collaboration - iNADO seeks a New CEO - iNADO Webinar - Anti-Doping Quiz for visually impaired Athletes - International Conference on Fitness Doping and Public Health (24-25 Oct., Copenhagen) - Collection of Anti-Doping Rules of International Federations - World Conference on Doping in Sport: Registration and Hotels - Collaboration between UKAD and Fitness Industry to curb doping in Gyms - Summary of 2018 Education Activities in Kazakhstan - New at the Anti-Doping Knowledge Center
Development of two complementary LC-HRMS methods for analyzing sotatercept in dried blood spots for doping controls
Development of two complementary LC-HRMS methods for analyzing sotatercept in dried blood spots for doping controls / Tobias Lange, Katja Walpurgis, Andreas Thomas, Hans Geyer, Mario Thevis (Bioanalysis 11 (2019) 10). - PMID: 31218901. - DOI: 10.4155/bio-2018-0313 _________________________________________________ Abstract Aim: sotatercept is a therapeutic Fc-fusion protein with erythropoiesis-stimulating activity. Due to a potential abuse of the drug by athletes in professional sports, a sensitive detection method is required. In sports drug testing, alternative matrices such as dried blood spots (DBS) are gaining increasing attention as they can provide several advantages over conventional matrices. Materials & methods: Herein, two complementary LC-high-resolution mass spectrometry (HRMS) detection methods for sotatercept from DBS, an initial testing procedure (ITP) and a confirmation procedure (CP) were developed and validated for the first time. Both methods comprise an ultrasonication-assisted extraction, affinity enrichment, proteolytic digestion and HRMS detection. Results & conclusion: For the multianalyte ITP, artificial samples fortified with sotatercept, luspatercept and bimagrumab, and authentic specimens containing bimagrumab were successfully analyzed as proof-of-concept. The validated detection methods for sotatercept are fit for purpose and the ITP was shown to be suitable for the detection of novel IgG-based pharmaceuticals in doping control DBS samples.
An Experimental Test of the Efficacy of Gain- and Loss-Framed Messages for Doping Prevention in Adolescent Athletes
An Experimental Test of the Efficacy of Gain- and Loss-Framed Messages for Doping Prevention in Adolescent Athletes / Lindsay R. Duncan, Laura Hallward. - (Substance Use & Misuse (2019) 18 June; p. 1-12). - PMID: 31210076. - DOI: 10.1080/10826084.2019.1626432 _________________________________________________ Abstract Background: Doping is a prevalent issue, not only among Olympians and professional athletes; young athletes and those at the sub-elite level have reported doping as well. Doping programs have been developed to target adolescent athletes and prevent doping initiation. The efficacy of primary doping prevention initiatives may be enhanced with health communication strategies, such as message framing. To date, there have been very few studies examining message framing among adolescents and none in the context of doping prevention. Objectives: The purpose of this study was to compare the efficacy of gain-framed and loss-framed messages on key psychological antecedents of doping among adolescent athletes. Methods: In a randomized controlled trial, 133 athletes aged 12 to 16 years old (Mage=13.73; 53% boys) from a variety of sports viewed either a gain- or loss-framed video. Intentions, attitudes, self-efficacy, and perceived norms were all assessed immediately before and after the videos. Results: Mixed between-within subjects ANOVAs revealed no differential influence for either message frame on changes in any of the outcomes. Attitudes, self-efficacy, and perceived norms all increased significantly over time for participants in both conditions. Conclusions/Importance: Overall, the findings suggest that a brief messaging intervention may have a beneficial influence on psychosocial constructs related to doping. There is no strong evidence to support definitive recommendations regarding optimal message framing for doping prevention among adolescent athletes. Keywords: Message framing, performance-enhancing drugs, prevention
In October 2018 the United States Anti-Doping Agency (USADA) has reported an anti-doping rule violation against the Paralympic Athlete Striley Jones after his A and B samples tested positive for the prohibited substance Stanozolol. After notification a provisional suspention was ordered. The Athlete filed a statement with evidence in his defence and he was heard for the American Arbitration Association (AAA) Commercial Arbitration Tribual. The Paralympic Athlete accepted the test result, denied the intentional use of the prohibited substance and requested the Panel for a reduced sanction. The Athlete claimed that one of his supplements he used was contamined and they were sent to a Lab for testing. Analysis of these supplements in question revealed that the supplement Nitro Tech Whey Protein was contaminated with Stanozolol which was recommended by the Athlete’s nutritionist. Reanalysis in the WADA Salt Lake City Lab confirmed the presence of Stanozolol. USADA was able to obtain an unopened case of six sealed containers from the manufacturer from the same lot number as the supplement in question, which, when tested, did not contain Stanozolol. As a result USADA contended that the Athlete failed to establish that the positive test was caused by a contaminated product and requested the Panel to impose a 4 year period of ineligibility on the Athlete. The Panel considered the facts and circumstances in this case and accepts that this is a different inquiry entirely from the requirements on ameliorating a sanction on the basis of fault or lack thereof, which analysis expressly requires the athlete to meet the balance of probabilities burden on source. It is entirely possible for an Athlete to prevail on the finding of lack of intention only to fail to establish source to get a further reduction; such a result is not logically inconsistent and is in fact possible under the very different tests provided by the IPC ADC. A majority of the Panel concludes that there was insufficient proof of lack of intention while the minority of the Panel concludes that there was sufficient proof of lack of intention. Consequently the Athlete did not establish by a balance of probability to the satisfaction of the majority of the Panel that the ingestion of the Stanozolol was unintentional. Unanimously, the Panel does not believe that the Athlete was a cheater and the Panel would have welcomed additional evidence to support that belief. Unfortunately, under the existing rules, that belief alone is insufficient and adducing such evidence is acknowledged by the Panel as being difficult to accomplish; the majority is of the view that its hands are tied to issue a sanction of 4 years ineligibility. Therefore by a Majority the Arbitration Tribunal decides on 17 June 2019 to impose a 4 year period of ineligibility on the Athlete starting on the date of the provisional suspension, i.e. on 17 October 2018.
Effect of hyperhydration on the pharmacokinetics and detection of orally administered budesonide in doping control analysis
Effect of hyperhydration on the pharmacokinetics and detection of orally administered budesonide in doping control analysis / I. Athanasiadou, A. Vonaparti, A. Dokoumetzidis, A. Saleh, M. Mbeloug, M. Al‐Maadheed, G. Valsami, C. Georgakopoulos. - (Scandinavian journal of medicine & science in sports (2019) 17 June). - PMID: 31206799. - DOI: 10.1111/sms.13499 _________________________________________________ Abstract The aim of the present study was to investigate if hyperhydration could influence the excretion and subsequent detection of budesonide (BDS) and its main metabolites (6β-hydroxy-budesonide and 16α-hydroxy-prednisolone) during doping control analysis by leading to concentrations below the WADA reporting level (30 ng/mL). The influence of hyperhydration on the plasma and urinary pharmacokinetic (PK) profiles of BDS and metabolites was also examined. Seven healthy physically active non-smoking Caucasian males participated in a 15-day clinical study. BDS was administered orally at a single dose of 9 mg on Days 1, 7 and 13. Hyperhydration was applied in the morning on two consecutive days, i.e., 0 and 24 hours after first fluid ingestion. Water and a commercial sports drink were used as hyperhydration agents (20 mL/kg body weight). Results showed no significant difference (P > 0.05, 95% CI) on plasma or urinary PK parameters under hyperhydration conditions for all the analytes. However, significant differences (P < 0.05, 95% CI) due to hyperhydration were observed on the urinary concentrations of BDS and metabolites. To compensate the dilution effect due to hyperhydration, different adjustment methods were applied based on specific gravity, urinary flow rate and creatinine. All the applied methods were able to adjust the concentration values close to the baseline ones for each analyte, however, specific gravity was the optimum method in terms of effectiveness and practicability. Furthermore, no masking of the detection sensitivity of BDS or its metabolites was observed due to hyperhydration either in plasma or urine samples.