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

11 Feb 2021

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.

C19-Steroids as androgen receptor modulators: Design, discovery, and structure-activity relationship of new steroidal androgen receptor antagonists

1 Sep 2006

C19-steroids as androgen receptor modulators : design, discovery, and structure-activity relationship of new steroidal androgen receptor antagonists / Padma Marwah, Ashok Marwah, Henry A. Lardy, Hiroshi Miyamoto, Chawnshang Chang. - (Bioorganic & Medicinal Chemistry 14 (2006) 17 (1 September); p. 5933-5947)

  • PMID: 16759873
  • DOI: 10.1016/j.bmc.2006.05.022


Abstract

Dehydroepiandrosterone (DHEA), the most abundant steroid in human circulating blood, is metabolized to sex hormones and other C19-steroids. Our previous collaborative study demonstrated that androst-5-ene-3beta,17beta-diol (Adiol) and androst-4-ene-3,17-dione (Adione), metabolites of DHEA, can activate androgen receptor (AR) target genes. Adiol is maintained at a high concentration in prostate cancer tissue; even after androgen deprivation therapy and its androgen activity is not inhibited by the antiandrogens currently used to treat prostate cancer patients. We have synthesized possible metabolites of DHEA and several synthetic analogues and evaluated their role in androgen receptor transactivation to identify AR modulators. Steroids with low androgenic potential in PC-3 cell lines were evaluated for anti-dihydrotestosterone (DHT) and anti-Adiol activity. We discovered three potent antiandrogens: 3beta-acetoxyandrosta-1,5-diene-17-one 17-ethylene ketal (ADEK), androsta-1,4-diene-3,17-dione 17-ethylene ketal (OAK), and 3beta-hydroxyandrosta-5,16-diene (HAD) that antagonized the effects of DHT as well as of Adiol on the growth of LNCaP cells and on the expression of prostate-specific antigen (PSA). In vivo tests of these compounds will reveal their potential as potent antiandrogens for the treatment of prostate cancer.

Analytical strategy for the detection of ecdysterone and its metabolites in vivo in uPA(+/+)-SCID mice with humanised liver, human urine samples and estimation of prevalence of its use in anti-doping samples

23 Mar 2021

Analytical strategy for the detection of ecdysterone and its metabolites in vivo in uPA(+/+)-SCID mice with humanised liver, human urine samples and estimation of prevalence of its use in anti-doping samples / S. Kraiem, M.Y. Al-Jaber, H. Al-Mohammed, A.S. Al-Menhali, N.J. AlThani, M. Helaleh, W. Samsam, S. Touil, A. Beotra, C. Georgakopoulas, S. Bouabdallah, V. Mohamed-Ali, M. Almaadheed, - (Drug Testing and Analysis (2021) 23 March)

  • PMID: 33759363
  • DOI: 10.1002/dta.3032


Abstract

Ecdysteroids are of interest as potential sport performance enhancers, due to their anabolic effects. The current study aimed to analyse levels of the most abundant ecdysteroid, ecdysterone (20-hydroxyecdysone, 20-OHE) in easily available dietary supplements, and, outline an analytical strategy for its detection, and that, of its metabolites, 1) following administration of pure 20-OHE to uPA(+/+)-SCID mice with humanised liver, 2) in a human volunteer after ingestion of two supplements, one with a relatively low, and the other a high, concentration of 20-OHE, and, 3) to estimate the prevalence of use of 20-OHE in elite athletes (n=1000). Of the 16 supplements tested, only five showed detectable levels of 20-OHE, with concentrations ranging from undetectable up to 2.3 mg per capsule. Urine of uPA(+/+)-SCID urine showed the presence of 20-OHE and its metabolite, 14 deoxy ecdysterone, within 24 hours (h) of ingestion. In humans, both the parent and the metabolite were detectable within 2 to 5 h of ingestion, with the metabolite being detectable for longer than the parent. After ingestion of a low dose supplement, the parent and metabolite were detectable for 70 h and 48 h, while following the higher dose it was 96 h and 48 h, respectively. Analysis of urines from athletes (n=1000) confirmed four positives for 20-OHE, suggesting a prevalence of use of 0.4%. Prevalence of its use by elite athletes was relatively low, however, this needs to be confirmed in other populations, and with other related ecdysteroids.

iNADO Update #2020-05

3 May 2021

iNADO Update (2021) 05 (3 May)
Institute of National Anti-Doping Organisations (iNADO)



Contents:

iNADO Community

  • French Sport Organizations hold the 20th National Conference for Doping Free Sport
  • A small NADO's Perspective - from the Importance of Education to Law Enforcement
  • UNIL opens Facebook Group to share Anti-Doping Expertise

Bulletin Board

  • iNADO Members elect new Board Members at Annual General Assembly
  • Governance in Anti-Doping: How to meet the Challenges
  • Capability Register of Member NADOs and RADOs is available now
  • Teleconference with WADA for iNADO Members

Athlete's Voice

  • Bridging the Gap: Researching Para-athlete's Experiences of Anti-Doping

People

  • New Director General at NADA India
  • AFLD announces new Secretary General

Science

  • Doping Authority Netherlands publishes a Paper on the Prevalence of Doping Substances in Sport Nutrition Supplements
  • New Detection Method developed for Prohibited Substances in Sample Analysis

Practical Development in Anti-Doping

  • Restoring Trust in Sport: Corruption Cases and Solutions – newly published Book calls on WADA to clarify the Discretion available to NADOs in their Response to Sub-Elite and Recreational Level Athletes
  • New EU Medical Device Regulation for Blood Sample Accessories
  • ITA will oversee Anti-Doping Programmes at European Games

Feature of the Month

  • Play True Day

iNADO Partners & Sponsors

  • New at the Anti-Doping Knowledge Center

CND 2021 Dopingautoriteit Decision Compliance Commission 2018001 N

27 Apr 2021

Related case:

ISR 2018 KNKF Decision Disciplinary Committee 2018001 T
March 26, 2018

On 26 March 2018 the ISR-KNKF Disciplinary Committee decided to impose a 4 year period of ineligibility on the Person after he tested positive for the prohibited substances Clenbuterol, Testosterone and 17α-methyl-5β-androstane-3α,17β-diol.

Hereafter in February 2021 the Dopingautoriteit has reported  that the Person had breached the imposed period of ineligibility through his participation in Germany into 2 powerlifting competitions.

After notification by the Doping Sanction Compliance Commission (CND) the Person failed to respond nor filed a statement in his defence. The CND renders a decision without a hearing based on the Parties' written submissions.

In support of the charges the Dopingautoriteit filed 2 online results lists as evidence showing that the Person had participated into the 2 powerlifting competitions in Germany in 2018 and in 2019.

Considering the evidence in this case the CND establishes that the Person through his participation into the 2 competitions in question indeed had breached the imposed period of ineligibility. Consequently a new period of ineligibility will be imposed on the Person without grounds for a reduced sanction.

Therefore the Doping Sanction Compliance Commission decides on 27 April 2021 to impose a new 4 year period of ineligibility on the Person starting on the date the current period of ineligibility shall end, i.e. on 4 January 2022.

The Person has not to pay the fees and expenses for this commission.

WADA - 2019 Anti-Doping Testing Figures Report

18 Dec 2020

2019 Anti-Doping Testing Figures / World Anti-Doping Agency (WADA). - Montreal : WADA, 2020

Contents:

  • Executive Summary - pp. 2-8 (7 pages)
  • Laboratory Report -– pp. 9-37 (28 pages)
  • Sport Report - pp. 38-174 (137 pages)
  • Testing Authority Report - pp. 175-313 (139 pages)
  • ABP Report-Blood Analysis - pp. 314-355 (42 pages)

Report Highlights

  • A 5.5% increase in the overall number of samples analyzed: 263,519 in 2018 to 278,047 in 2019.
  • A slight decrease in the total percentage of Adverse Analytical Findings (AAFs): 1.05% in 2018 (2,774 AAFs from 263,519 samples) to 0.97% in 2019 (2,702 AAFs from 278,047 samples).
  • About 60% of WADA-accredited Laboratories saw an increase in the total number of samples recorded.
  • An almost similar total number and percentage of non-Athlete Biological Passport (ABP) blood samples analyzed: 9.3% in 2018 (24,495 of 263,519) and 9.1% in 2019 (25,339 of 278,047).
  • An increase of 16% in the number of ABP blood samples tested: 31,265 in 2018 to 36,401 in 2019.
  • An increase in AAFs reported for Erythropoiesis Stimulating Agents (ESAs), Growth Hormone (GH) and Growth Hormone Releasing Factors (GHRFs).

The World Anti-Doping Agency (WADA) has published its 2019 Testing Figures Report (2019 Report), which summarizes the results of all the samples WADA-accredited Laboratories analyzed and reported in WADA’s Anti-Doping Administration and Management System (ADAMS) in 2019.

This is the fifth set of global testing figures under the version of the World Anti-Doping Code (Code) that came into effect in January 2015. The 2019 Report – which includes an Executive Summary and sub-reports by Laboratory, Sport, Testing Authority and Athlete Biological Passport (ABP) Blood Analysis – includes in- and out-of-competition urine samples; blood and ABP blood data; and, the resulting AAFs and Atypical Findings (ATFs).

WADA - 2018 Anti-Doping Rule Violations (ADRVs) Report

10 Dec 2020

2018 Anti-Doping Rule Violations (ADRVs) Report / World Anti-Doping Agency (WADA). - Montreal : WADA, 2020. - Report compiled based on decisions received by WADA before 2 March 2020


  • The Report highlights 1,923 confirmed Anti-Doping Rule Violations (ADRVs) in 2018, involving individuals from 117 nationalities and across 92 sports
  • 1,640 ADRVs came from Adverse Analytical Findings and 283 from non-analytical, evidence-based intelligence

The World Anti-Doping Agency (WADA) has publishes its sixth annual Anti-Doping Rule Violations (ADRVs) Report, which is the official set of such figures under the World Anti-Doping Code. As usual, the Report is available in a PDF version as well as a dynamic, Excel version that illustrates the ADRV results in an interactive fashion.

The Report illustrates doping offences committed in global sport during 2018. It highlights that there were a total of 1,923 ADRVs recorded in that year. This represents a 6.5% increase relative to the 2017 figure of 1,804, which in turn was 13% more than 2016.

1,640 of the ADRVs came out of Adverse Analytical Findings (AAFs), commonly known as ‘positive’ results. The remainder were derived from investigations and evidence-based intelligence into 267 violations committed by athletes and 16 by athlete support personnel (ASP).

The report contains all ADRV decisions reported to WADA by Anti-Doping Organizations (ADOs). These decisions include those from AAFs reported in samples collected by ADOs in 2018 as well as from non-analytical ADRV decisions rendered in 2018.

As with previous years, the beginning of the report comprises an introduction and an executive summary highlighting key data. The first and second sections present the Results Management outcomes (including ADRVs) of all AAFs detected by WADA-accredited Laboratories for samples collected in 2018 from athletes in- and out-of-competition. They are presented by sport, discipline (Section 1) and testing authority (Section 2).

Section 3 includes ADRVs that resulted from non-analytical findings committed by athletes (presented by sport and nationality) and by ASP (presented by nationality).

Section 4 indicates the total number of ADRVs in 2018, which includes AAFs that resulted in an ADRV plus all non-analytical ADRVs. It presents the data by sport and nationality. It is further broken down into type of samples (urine or blood), type of test (in- or out-of-competition) and athlete gender.

CAS 2020_A_7528 Chistian Coleman vs World Athletics

15 Apr 2021

CAS 2020/A/7528 Christian Coleman v. World Athletics

Related case:

World Athletics 2020 WA vs Christian Coleman
October 22, 2020


In June 2020 the Athletics Integrity Unit (AIU) of World Athletics reported an an anti-doping rule violation against the American Athlete Christian Coleman for his Whereabouts Filing Failure and 2 Missed Tests in a 12 month period.

Consequently the World Athletics Disciplinary Tribunal decided on 22 October 2020 to impose a 2 year period of ineligibility on the Athlete.

In First Instance the Panel rejected the Athlete's allegations that the authorities had developed a strategy in an effort to catch him out, and finds that he persisted in an exculpatory version of events as to what happened on 9 December 2019. The Panel deemed that the Athlete's behaviour was very careless at best and reckless at worst.

Hereafter in November 2020 the Athlete appealed the Decision of 22 October 2020 with the Court of Arbitration for Sport (CAS). The Athlete requested the Panel to set aside the Appealed decision and to impose a reduced sanction.

The Athlete did not challenge the Missed Test of 16 January 2019 or the Filing Failure of 26 April 2019. The challenge is
limited to the Missed Test of 9 December 2019. It follows that, if the Missed Test of 9 December 2019 is sustained, then there will be three Missed Tests and/or Filing Failures within a 12-month period and an ADRV will have been committed.

The Athlete asserted that the Doping Control Officer (DCO) did not do what was reasonable in the circumstances to locate the Athlete on 9 December 2019. Specifically because the World Athletics had instructed the DCO not to call the Athlete thereby precluding the DCO from doing what was reasonable.

World Athletics contended that the Athlete in fact was not home at any time during the 60-minute slot. Futher the DCO did what was reasonable in the circumstances to try and locate the Athlete at that time on that date. The fact that the DCO was instructed not to call the Athlete does not mean that the DCO failed to act reasonably.

The Panel concludes that, on 9 December 2019, the DCO did do what was reasonable in all the circumstances, given the nature of the residential premises and the time of day, to try to locate the Athlete at his home in Lexington, Kentucky. On the evening of 9 December 2019, the DCO knocked on the door and rang the bell in such a manner, as is accepted by the Athlete, that if anyone were home at the time they would have been made aware that the DCO was there.

The Panel is more than satisfied that, had the Athlete been at home, the attempts made by the DCO on the night in question would have been perfectly adequate to let the Athlete know that someone was at the door. Had he been at home and answered the door, the test could have been conducted without issue.

The Panel does not accept the Athlete's evidence and finds the Athlete's account wholly implausible. The Panel concludes that there was no evidence supporting any claim that the Athlete was at the location identified by him at any time during the 60-minute slot specified by him for testing on 9 December 2019.

By contrast the Panel holds there is no reason at all not to accept the evidence of the officers that they were at the Athlete's home on 9 December 2019 during the 60-minute slot.

The Panel considers the Athlete's conduct on 9 December 2019, and deems that the his degree of fault falls to be characterised as "medium", i.e. within the 16-20 months band, with a midpoint of 18 months.

Therefore the Court of Arbitration for Sport decides on 15 April 2021 that:

1.) The appeal filed by Mr Christian Coleman against World Athletics on 19 November 2002 is partly upheld.

2.) The decision of the AIU Disciplinary Tribunal on 22 October 2020 is set aside and replaced as follows:

Mr Christian Coleman has committed an Anti-Doping Rule Violation under Article 2.4 of the World Athletics Anti-Doping Rules and shall serve a period of ineligibility of eighteen (18) months as from 14 May 2020.

3.) The award is pronounced without costs, except for the Court Office fee of CHF 1,000 (one thousand Swiss Francs) paid by Mr Christian Coleman, which is retained by the CAS.

4.) Mr Christian Coleman is ordered to pay World Athletics a total amount of CHF 4,000 (four thousand Swiss Francs) as contribution towards the expenses incurred in connection with these arbitration proceedings.

5.) All other motions or prayers for relief are dismissed.

CAS 2020_ADD_12 BWF vs Clement Krobakpo

22 Jan 2021

CAS 2020/ADD/12 Badminton World Federation v. Clement Krobakpo

In July 2020 the Disciplinary Committee of the Organizing Committee of the African Games decided to disqualify the Nigerian badminton player Clement Krobakpo after his sample tested positive for the prohibited substances Clenbuterol, Heptaminol and Octodrine. The case was referred to the Badminton World Federation (BWF) and hereafter in August 2020 the BWF reported an anti-doping rule violation against the Athlete.

In September 2020 the BWF filed a request for Arbitration with the Anti-Doping Division of the Court of Arbitration for Sport (CAS ADD) as first-instance authority. The Sole Arbitrator renders a decision without a hearing based on the Parties' written submissions. 

The Athlete accepted the test result, admitted het violation and denied the intentional use of the substances. He could not explain the presence of the low concentration of Clenbuterol in his sample and suggested that imported contaminated meat in Nigeria had caused the positive test. Further he asserted that the energy drink Freedom Juice he had used was the source of Heptaminol and Octodrine. He had mentioned this product on the Doping Control Form while he was unaware that it contained the ingredient 2-aminoisoheptane (Octodrine). 

The BWF accepted that the energy drink Freed Juice was the source of the Heptaminol and Octodrine and that this violation was unintentional. Yet the BWF contended that the Athlete failed to establish the how the prohibited substance Clenbuterol had entered his system. 

The Sole Arbitrator concludes that the Athlete committed an anti-doping rule violation and that it is undisputed that the energy drink he had used was the source of the positive test. Further the Arbitrator holds that the Athlete only had offered speculation to explain the meat contamination and consequently that this defence must be rejected. Finally the Sole Arbitrator considers that there were substantial delays in the proceedings not attributed to the Athlete. 

Therefore the Court of Arbitration for Sport decides on 22 January 2021 that:

  1. The request for arbitration filed by the Badminton World Federation on 25 September 2020 against Mr. Clement Krobakpo is upheld.
  2. Mr. Clement Krobakpo committed an anti-doping rule violation in accordance with the Badminton World Federation’s Anti-Doping Rules applicable to the 2019 African Games in Rabat, Morocco.
  3. Mr. Clement Krobakpo is sanctioned with a 4-year period of ineligibility starting from 16 October 2020.
  4. All competitive results obtained by Mr. Clement Krobakpo from 25 August 2019 through the date of his provisional suspension are disqualified, with all resulting consequences, including forfeiture of medals, points and prizes.
  5. (…).
  6. (…).
  7. All other motions or prayers for relief are dismissed.

CAS 2020_ADD_11 IOC vs Vladimir Nikolov

15 Oct 2020

CAS 2020/ADD/11 International Olympic Committee v. Vladimir Nikolov

Mr Vladimir Nikolo is a Bulgarina volleyball player at the London 2012 Olympic Games. 

In 2018, the International Olympic Committee (IOC) decided to perform further analyses on certain samples collected during the 2012 Olympic Games. These additional analyses were performed with analytical methods which were not available in 2012. 

In January 2020 the International Testing Agency (ITA), on behalf of the IOC, reported an anti-doping rule violation against the Athlete after his 2012 A and B samples tested positive for the prohibited substance Methyltestosterone. 

Hereafter in August 2020 the International Olympic Committee (IOC) filed a request for Arbitration with the Anti-Doping Division of the Court of Arbitration for Sport (CAS ADD) as first-instance authority. The Sole Arbitrator renders a decision without a hearing based on the Parties' written submissions. 

The Athlete accepted the test result, admitted the violation and denied intentional use. He was tested before without issues and could not explain how the substance had entered his system. He assumed that a contaminated supplement might have been the source of the positive test since only a very low concentration of the substance was found in his samples. 

The IOC contended that the presence of the prohibited substance had been established in the Athlete's sample and accordingly that he had committed an anti-doping rule violation. 

The Sole Arbitrator concludes that there is sufficient proof that the Athlete committed an anti-doping rule violation. Any mitigating circumstanced invoked by the Athlete in his defence, even if proven, are not relevant to establish whether an anti-doping rule violation was committed. The Sole Arbitrator deems that the Athlete may have an opportunity to explain the circumstances at a later stage of the prosecution of the anti-doping rule violation. 

Therefore the Court of Arbitration for Sport decides on 15 October 2020 that:

  1. The request for arbitration filed by the International Olympic Committee on 28 August 2020 against Mr. Vladimir Nikolov is upheld.
  2. Mr. Vladimir Nikolov committed an anti-doping rule violation in accordance with the International Olympic Committee’s Anti-Doping Rules applicable to the XXX Olympiad, London 2012.
  3. Mr. Vladimir Nikolov shall return the Olympic diploma and pin he received on the occasion of the XXX Olympiad, London 2012.
  4. (…).
  5. (…).
  6. All other motions or prayers for relief are dismissed.

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