New Sports Doping Agent FG-4592 Not the Only HIF Drug Available to Athletes

fg-4592 What drugs are athletes using to dope? This is one of the most commonly asked questions in the realm of sports anti-doping. Recently the answer has been provided in glaring form. During the week of July 29, Dr. Don Catlin, BSCG’s chief science officer and former longtime director of the UCLA Olympic Analytical Laboratory, was interviewed by the New York Times regarding a new drug called FG-4592, which was detected in tests of at least two elite cyclists.

AstraZeneca, one of the drugs’ developers, summarizes FG-4592 as “a small molecule inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase. HIF is a protein that responds to oxygen changes in the cellular environment and meets the body’s demands for oxygen by inducing erythropoiesis, the process by which red blood cells are produced.”

FG-4592 is available in pill form and is orally active, unlike its cousin, recombinant erythropoietin, or EPO, which must be injected. Some have dubbed FG-4592 as oxygen in pill form. This new drug is a breakthrough for anemia treatment and other similar blood ailments.  doping-271623_640Unfortunately, an effective blood boosting drug in pill form is also the Holy Grail for endurance dopers. Though FG-4592 remains in third-stage clinical trials around the world, it is widely available as a research chemical on the Internet. Its apparent arrival in elite sport is troubling, yet predictable.

Similar to EPO, HIF drugs like FG-4592 help increase oxygen carrying capacity by spurring the production of red blood cells. Some researchers believe HIF stabilizers might be even more effective than EPO as they can help stimulate iron absorption and suppress the inflammation of cytokines.[1] FG-4592 was recently added to the WADA (World Anti-Doping Agency) Prohibited List for 2015, as have cobalt and other HIF stabilizers and activators in general.  No other HIF drugs are named though they would be prohibited if they are detected.

According to PubChem’s listing of Chemical Vendors, there are 18 suppliers of FG-4592 worldwide . One of the vendors, the Houston-based company APExBIO, has eight HIF-related biochemicals available on its website including BAY 87-2243, 2-Methoxyestradiol, PX 12, ML 228, KC7F2, Chetomin, DMOG, and its top seller, IOX2 (Glycine). On PubChem, there are 251 Related Compounds with Annotation to explore.

Recent positive drug tests of two elite cyclists suggest athletes have managed to obtain FG-4592 for use as a performance-enhancer. Though the chemical vendors listed on PubMed are not marketing the drug to athletes, another site does not seem as scrupulous, as it sells research peptides like FG-4592 alongside an array of “performance enhancers.”  Some research peptides at www.superhumanstore.com overlap the list of performance enhancers. Numerous drugs on the WADA Prohibited List are available on this site including Aicar, CJC-1295 (a growth hormone secretagogue), Erythropoietin-mimetic peptide 17 (EMP17), GHRP-2, Sermorelin, Thymosin Beta- 4 and more. Similar drugs are available that are not included on the WADA Prohibited List by name, like BAY 87-2243 and Follistatin 344 (a myostatin inhibitor).

The average cyclists pictureprofessional cyclist in the UCI Tour makes $142,000, according to Ernst & Young.  Top riders can earn up to $5 million. Currently, the average dose of FG-4592 is recommended at 1-2mg/kg, 3 times a week, so $780 for 500mg will buy a two- week’s supply. An athlete could buy a year’s supply for around $20,280. This is a relatively affordable rate, even to an average Tour rider. With the difference between the average salary and the top salaries in elite cycling so significant, the financial incentives to use this new drug, or its cousins, remains high.

The good news is FG-4592 is detectable with drug tests. Similar developing drugs will undoubtedly be pursued and tried by athletes in the not-too-distant future. Whether these other options, particularly those not specified on the WADA Prohibited List, are detectable only time will tell. One thing history has proven, these will not be the last athletes to test positive for a new sports doping agent.

By Oliver Catlin and Joe Taylor

[1] Medscape  (http://www.medscape.org/viewarticle/548667)

The Monetary Gap – One Reason for the Lance Armstrong Affair

LA photo from TVYesterday much of the world had to watch Oprah to see Lance Armstrong confess his doping for the first time.  Even Lance agrees that should have happened long ago. 

One of the most troubling elements of all of this is that drug testing began in the Olympics in 1968 more than 44 years ago and yet the system is still unable to distinguish who is a clean athlete.  Every decade we are faced with a groundbreaking scandal, and multiple times a year we are faced with an ordinary scandal resulting from doping in sport.  Just last week we finished a baseball hall of fame vote where a whole generation of players got snubbed largely because of doping, and yet it seemed ordinary. 

Lance Armstrong, Ben Johnson, Marion Jones, Tim Montgomery, Barry Bonds, Roger Clemens… the list is long and spans all sports and generations when it comes to sport heroes and champions who have fallen, some even sacrificing their lives like Tommy Simpson, from using performance-enhancing drugs.  The question facing us all is why and what should we do about it, in much the same way we ask why and what to do about gun violence after witnessing the Newtown disaster. 

Now some may say hold on, you are way out of line.  There is no way to compare innocent children dying in a horrifying massacre to the performance-enhancing drug problem.  While we would agree with that in large part, we also point out that children are tragically affected by performance-enhancing drugs, figuring they have to use them to compete.  Sadly, some of our children even sacrifice their lives in pursuit of steroids and other drugs.  Just ask the Hooton’s, or the Garibaldi’s, or the Marrero’s or the other parents that have paid the ultimate price in losing a child to the use of performance-enhancing drugs. 

We consider the annual budget of the World Anti-Doping Agency at ~$28 million annually and the United States Anti-Doping Agency at $14 million.  We assume UK Sport and Australian Sports Anti-Doping Authority are equivalent to USADA for another $28 million.  The NFL spent $10 million in 2011.  We will put MLB at $10 million as well although their updated new program likely will come with additional cost.  The sport of cycling was estimated to spend $4.7 million and tennis (ITF) $1.3 million per year in 2011 for another $6 million.  If we assume there are 150 other countries and sporting bodies spending an average of $1-2 million annually on anti-doping, that adds another $150-300 million.  All said we estimate the total annual anti-doping budget worldwide to be $246-396 million, which compares to the budget of a small pharmaceutical company – and our estimate is probably on the high side. 

At the same time, you consider that Lance Armstrong made an estimated $17.5 million in endorsements alone in 2005.  Alex Rodriguez, another previous doper, makes $29 million per year in salary alone.  Annual budgets for professional cycling teams range from several million up to $25 million for a team like Sky.  The median team payroll in Major League Baseball is around $90 million while the total payroll for the league is a staggering $2.94 billion.  The total payroll in the NFL is even higher at almost $3.4 billion.  Finally consider the $3.2 billion in endorsement contracts for Nike athletes alone over the next 5 years.  All told, professional and Olympic athletes and teams have easily more than $10 billion in annual resources. 

When Lance Armstrong’s endorsements plus A-Rod’s salary alone totals more than $46.5 million, eclipsing the WADA and USADA annual budgets by $4.5 million.  When the drug-testing programs for MLB and NFL represent 0.3% of annual player salaries.  When the estimated annual amount spent worldwide on anti-doping testing, legal matters and research at ~$246-396 million represents 2-4% of the more than $10 billion in resources available to athletes perhaps we begin to see the scope of the problem.  Those who want to dope can afford to beat the system; at present the monetary gap is simply too great for the system to overcome. 

Now we consider the response.  There have already been countless hours of media content alone dedicated to Lance Armstrong.  We tried to estimate the dollars spent and considered 500 media outlets spending an average of $10,000 each on the coverage.  That would be $5 million alone spent covering the issue worldwide, by the end of this whole affair it is likely to be 10 or 50 times that amount, and our estimate is likely conservative. 

Those of us in the anti-doping community don’t expect $6 billion to be dropped off anytime soon, but it would be nice to see the resources available to anti-doping double or triple at least.  If we can’t afford to give anti-doping a fighting chance by providing the movement with the financial resources needed to effectuate change, then we are part of the problem and we can settle in for a continuing parade of scandals. 

It is up to sport and those that care about it to ensure adequate resources are available to establish and maintain a reality of clean competition.  The athletes, sport, and the next generations of athletes and sports fans deserve a drug testing system that can deliver to the world clean sporting champions, ones we can believe in and trust.  With an outmatched system that can’t expose dirty athletes, even athletes who want to compete clean feel they have to dope to win, and we simply can’t accept that reality.  The risks are too great to sport and the individuals who dedicate their lives to it. 

But it is not just about the money, it is about finding real solutions that can improve the drug-testing system and approach in place today, with or without more resources.  Stay tuned as our dinner conversations have been generating some interesting ideas….

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Egregious error in high-profile Sports Illustrated story by Selena Roberts & David Epstein exposed

Los Angeles,  March 29, 2011

Egregious Error in Sports Illustrated Story by Selena Roberts & David Epstein Exposed

USOC Committee Meeting Notes Reveal Truth

Anti-Doping Research (ADR) has obtained a copy of meeting notes of the United States Olympic Committee (USOC) meeting of March 2000, referenced as “the minutes” in the misleading Jan. 24 Sports Illustrated Lance Armstrong story by Selena Roberts and David Epstein.  Attorneys at Time, Inc. finally provided an excerpt of the notes after repeated requests.

As suspected, the notes show that contrary to Roberts and Epstein’s claims, the committee, with Dr. Catlin often leading the way, was not only trying to do everything it could within the existing framework to ensure an effective doping system in the United States, it was attempting to raise the testing standards and make them more stringent for athletes.

The meeting notes are crucial for providing the appropriate context and demonstrate that Roberts and Epstein’s written and press interview statements charging that Dr. Catlin and officials discuss in the meeting how “to informally test athletes–not to sanction them but to help them avoid testing positive at the Olympics” are patently false.  Indeed, the writers and editor(s) either do not understand or willfully ignore the context of the discussion.

To help shed light on the situation and be as transparent as possible, Dr. Catlin and ADR are taking the step of releasing the USOC meeting notes.  Because the discussion is complex and difficult to follow, Dr. Catlin is offering a statement on the context of the meeting and an annotated version of the notes that adds helpful and insightful comments.  You may click the following links to pdfs of Dr. Catlin’s Statement and Annotated Notes as well as the Raw Version of the Notes.

The primary issue at hand was how to apply Dr. Catlin’s new, complex, and, at that time, legally untested Carbon Isotope Ratio (CIR) test to confirm testosterone use in U.S. athlete samples prior to the Summer Olympics in Sydney.  For his part, Dr. Catlin wanted to see his test implemented in the United States and was doing what he could to advance it.

“I want to see better and better doping (control),” he said.  “And it’s (the CIR test is) ready to go… and I submit that there’s tons and tons of political and legal reasons not to do it and to do it.  I’m making a statement that I’m willing to go to court to defend the test, and I wouldn’t have made that statement until very recently.”

The group was reviewing the rules for screening for testosterone use by applying the testosterone to epitestosterone (T/E) ratio to see how the follow-up CIR confirmation test could be applied.  A key issue discussed was what constituted an initial positive T/E finding.  According to the IOC, the relevant governing body at the time, only a sample with a T/E ratio of 6:1 or higher was an initial positive.  The IOC rules included the ability to use CIR for follow-up testing while the USOC protocol under discussion did not mention CIR use.

Dr. Catlin and others on the committee considered implementing tougher standards than the IOC rules allowed, by applying the CIR test to samples in which the T/E ratio was in the more stringent 4:1 to 6:1 range.  In fact, Dr. Catlin had lobbied the IOC to adopt the more stringent T/E range, a point he mentions in the meeting.  The meeting notes reveal the group struggling with how to use CIR for sanctioning purposes given the concern that prosecution of testosterone doping offenses in which the T/E ratio was less than 6:1 would be unsuccessful under the current IOC framework.

The members discussed if and how U.S. athletes should be introduced to the new test, with some wanting to warn athletes and others not wanting to warn them.  Those who argued for warning athletes were doing so out of a desire to compel as many of them as possible to clean up—the point of doping control—and for a time the IOC required such warnings.  Again contrary to Roberts and Epstein’s claims, Dr. Catlin argued that alerting the USOC, so that they could warn athletes, was not necessary.  “I don’t (care) whether you guys are alerted in advance,” he said.  “If we want to put a test in before the Games, we’ll do it.”

As a potential compromise, a committee member floated the idea of doing an informal study applying the CIR test to a group of 50 samples in which the T/E ratio measured in the more stringent 4:1 to 6:1 range.  The purpose of this proposal was to assess the potential of doping prevalence, as good, credible science-based anti-doping programs do.  Research studies are, by proper protocol, anonymous, as Dr. Catlin told the group.

Although Dr. Catlin believed in the science behind the CIR test and was pressing to use it for sanctioning purposes, he was open to the idea of a compromise because he believed that the results would help push the IOC to adopt the more stringent standard.  A precedent had been established with similar research conducted by the IOC at the 1998 Nagano Winter Olympics, he noted, though he remained, as always, opposed to “no-penalty testing.”

In the end the motion to conduct the research study was withdrawn, and no such study was conducted.  Five years later, in 2005, the World Anti-Doping Agency lowered the benchmark for an initial positive testosterone test result to a T/E ratio of 4:1.

The CIR test is considered revolutionary and has proven highly effective; despite many challenges by athletes testing positive, the Court of Arbitration for Sport has never found any fault with it.

The blatant mischaracterization of the USOC meeting is merely one of several egregious errors Anti-Doping Research has found in the Jan. 24 Sports Illustrated feature story by Selena Roberts and David Epstein.

Don Catlin, M.D., responds to Sports Illustrated story by Selena Roberts & David Epstein on Lance Armstrong

Los Angeles, January 27, 2011

Statement of Anti-Doping Research (ADR) on recent Sports Illustrated story by Selena Roberts and David Epstein:

A high-profile feature story on Lance Armstrong in the Jan. 24 issue of Sports Illustrated has led to NPR and CNN interviews for its writers, Selena Roberts and David Epstein.  Unfortunately, both their story and their interviews contain innuendo and mischaracterize key elements, including perhaps most notably, urine tests performed by Don Catlin, M.D., back in the mid-1990s.

Dr. Catlin, a widely respected pioneer in the field of anti-doping in sport, wishes to set the record straight.  In the detailed statement that follows, he demonstrates his respect for the truth as he knows it as well as his commitment to transparency.

As he states, he was not aware that the A samples allegedly testing high for testosterone in 1993, 1994 and 1996 were Lance Armstrong’s, if, in fact, that is the case.  We have seen no evidence to suggest that it is.

Sports drug-testing laboratories are required to use codes, not names, for samples to protect all parties and the sanctity of the process.  Dr. Catlin and his team followed those rules during his tenure as director of the UCLA Olympic Analytical Lab.

Further, during the years in question, Dr. Catlin and the world at large did not even know who Lance Armstrong was.  Mr. Armstrong had not yet established himself as a champion cyclist and Tour de France winner.

We find that the elements of Ms. Roberts and Mr. Epstein’s story that involve Dr. Catlin lack credibility.  The reporters have delivered a story that misrepresents the truth.

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Statement of Don Catlin, M.D.

Background:

I was the founder and Director of the UCLA Olympic laboratory from its inception in 1982 until I left UCLA 25 years later (2007).  The lab was accredited by the International Olympic Committee (IOC) in 1983 and it was the first sport testing lab in the United States.  The laboratory performed the testing for the 1984 Los Angeles Olympic Games, the steroid testing for the 1996 Atlanta Olympic Games, and the testing for the 2002 Salt Lake City Olympic Games.  During those years the sample numbers grew from 2,000 to over 50,000 samples per year making it the largest sport-testing lab in the world.

During my tenure, I performed drug testing on behalf of the United States Olympic Committee (USOC), the United States Anti-Doping Agency (USADA), the National Football League (NFL), the National Collegiate Athletic Association (NCAA), Major League Baseball (MLB), the World Anti-Doping Agency (WADA), the U.S. federal government and many other organizations.  I have spent my whole career dedicated to building the ethos and system of anti-doping that we have today.  Violating that system in any way would be anathema to everything I believe in.

As a laboratory director, I often responded to legitimate requests for information about the results.  Guiding those requests and the whole testing process are the cardinal features of all sport testing contracts: 1) samples are identified only by a code number, 2) only the testing agency (for example USADA) can connect the name of the athlete to the code number, and 3) nobody at the laboratory knows the name of the athletes.  The testing is anonymous.

For as long as I can remember, laboratory directors and their staffs have been forbidden by anti-doping agencies from discussing cases with the media.  Today, this is formalized within the World Anti-Doping Agency’s Code of Ethics of the International Standard for Laboratories.

On Wade Exum:

Wade Exum was the Director of Drug Control at the USOC from 1991 through 2000.  The article refers to Exum’s lawsuit against the USOC upon his termination and also to Exum’s allegations of “letting positive drug tests slide.”  As the article mentions, “Exum’s lawsuit was dismissed for lack of evidence.”

Later in the article, Wade Exum is quoted as saying “Out of tens of thousands of tests purchased during my tenure as Director of Drug Control at the USOC, I can remember only one T/E ratio being called positive.”

I have reviewed my records and they reveal that the UCLA Lab reported more than 25 urine samples with T/E values greater than 6 to the USOC between 1992 and 2000.  As the lab director, reporting to the USOC fulfilled my obligations I had no authority or ability to take further action against the athlete; the authority to take action against the athlete rested solely with the USOC or other appropriate agency.  I would not have the ability to take further action against an athlete as I only work with sample codes and would not know the identities of those testing positive or negative.

On the minutes of USOC anti-doping committee meetings:

I spoke with the co-author of the Sports Illustrated article, David Epstein, in a telephone conversation between January 13-19, just before his article was published.  During the conversation, I asked for a copy of the meeting minutes to which the article refers.  It is important to understand the context of the meeting to appropriately comment.  Mr. Epstein told me that he either could not or would not provide the meeting minutes.  Since the publication of the article, I have asked the USOC for a copy of the minutes but have not yet received one.  I have also formally requested a copy from the editors of SI through counsel and am awaiting a response.

I have attended hundreds of meetings in my career and cannot recall all of the topics discussed.  It is impossible to comment on the context of a meeting after being read a few lines from minutes that are almost eleven years old.  I am confident that if provided with the context I could easily explain any statements in the minutes and their relevance to the advancement of the anti-doping system in general as that has always been my creed.

On the USA Cycling letter to Catlin from May 1999:

The article describes a May 1999 letter from USA Cycling to me asking for the testosterone-epitestosterone (T/E) ratios “for a cyclist identified only by his drug-testing code numbers.”  Allegedly, “a source with knowledge of the request says that the cyclist was Lance Armstrong.”

The article suggests that the letter referred to one cyclist, but the letter is not directly quoted.  It is unclear if the letter in fact requested results for one cyclist or whether it was a general request for results on a group of lab codes not tied to any individual.  Again, I have asked David Epstein for a copy of the letter.  As of January 26, it has not been provided.

The article makes it clear that the request included only code numbers.  As a result, I could not have known the identity of the athlete or athletes included in the request.  Regardless of the specifics, such requests were very common and routine; I had numerous such requests in the course of my career.

Catlin’s letter to USA Cycling dated June 4, 1999 (see 4 numbered comments):

An excerpt of the article describes my response to USA Cycling:

“In a letter dated June 4, 1999, Catlin responded that the lab couldn’t recover a total of five of the cyclist’s test results from 1990, 1992 and 1993, adding, ‘the likelihood that we will be able to recover these old files is low.’ The letter went on to detail the cyclist’s testosterone-epitestosterone results from 1991 to 1998, with one missing season: 1997, the only year during that span in which Armstrong didn’t compete. Three results stand out: a 9.0-to-1 ratio from a sample collected on June 23, 1993; a 7.6-to-1 from July 7, 1994; and a 6.5-to-1 from June 4, 1996.”

Again, I have asked for a copy of this letter, but it has not been provided.

1 – Background necessary to understand the testing methods and reporting:

The urine samples are collected at the testing site by trained collectors who follow a detailed protocol and do not work at the lab.  Each sample is split into two portions (A and B) while the athlete observes.  Samples from one athlete are labeled, for example: 123456A and 123456B.  At the lab, the A samples are screened and the B samples are stored intact.  If the A screen is negative, the lab reports a negative result to the agency.  If the A shows evidence of a drug, the laboratory performs an A confirmation.  If the A confirmation is positive, the laboratory reports an adverse result to the agency.  The agency informs the athlete, who may choose to make an appointment for a representative to come to the laboratory to watch his or her B sample confirmation.  If the B confirmation confirms the adverse finding, the laboratory reports an adverse result to the agency that requested the test, the relevant national governing body, and an international body such as the IOC or WADA (The details of the reporting pathway changed over the years).

2 – On the request for data from five samples from 1990, 1992 and 1993:

In 1990, 1992 and 1993 we did not have the consistent electronic archive options that are available today.  The data was stored on magnetic tape and other similar media that were not always consistent in their performance.  When older data could not be found it was usually because the storage medium had deteriorated and the data was no longer in archive directories.  In the 1990s, WADA did not exist and the labs were managed by the IOC.  The IOC-accredited laboratories were not required to retain the data on samples declared negative, although it was our practice to retain all electronic data while I was at UCLA and respond to requests similar to the alleged request from USA Cycling if the data still existed.

3 – On the three T/E results from 1993, 1994 and 1996 discussed in the article:

When the laboratory would have originally received the samples in question, identified only by a number, not only did no lab employee, including myself, know the name of the athlete, but nobody knew whether the athlete had ever been tested before or would ever be tested again.  All three were reported long before Armstrong won his first Tour de France and became famous; I had no idea who he was at the time.  In a response letter of the sort described from June 4, 1999, I would merely be describing results that had been obtained and reported independently from one another several years earlier.

It was not an unexpected occurrence to have samples with screen T/E ratios between 6.0 and 7.5 not confirm.  It would be less likely, however, that a sample that screens at 9.0 does not confirm.

4 – Background necessary to understand T/E ratio results:

To determine whether a sample’s T/E is greater than 6, the lab must measure it.  Inherent to any and all kinds of measurements is a certain amount of “measurement uncertainty.”  To confirm a T/E greater than 6, statistical analysis of the measurements obtained for the sample and standards must meet certain criteria.  Sometimes those strict criteria are not met by samples whose T/E is above 6.  In addition to these mathematical criteria, a host of other requirements must be met in order to confirm a positive T/E result, which would be described in the Standard Operating Procedure (SOP) relevant at the time.  In other words, the lab, accreditation, and drug-testing system require the lab to report positive results only when the data meet the strict standards laid out in the SOP.

The T/E ratio is a very complicated test and the interpretation of the test results are equally difficult.(3,4)  A ratio greater than 6 does not prove that the individual used testosterone.  It does mean that additional tests are necessary.  Nowadays, thanks to research conducted by a handful of scientists, many of which I have had the pleasure of working with, laboratories perform the Carbon Isotope Ratio test to help clarify the results.  However, before the CIR test was available starting in the late 1990s, one approach was to collect three more samples from the athlete at least several weeks apart and study the results.  Exactly how to do this is explained in a peer-reviewed paper that I wrote with colleagues and published in 1996.(4)  Reading these papers today will provide the serious student of this issue with considerable insight.

On Mark Levinstein’s visit to the UCLA Olympic Analytical Lab in 2005:

As a doping-control lab director and anti-doping scientist, a key element of my mission is to educate students, attorneys, journalists, and the public about relevant issues surrounding drugs in sports.  This includes educating attorneys about how lab testing is done.  I have done this countless times over the years, sometimes one on one, sometimes in small groups and occasionally with very large groups.  Examples include delivering a two-day educational seminar to some 30 North American arbitrators in 2001.  In addition, I have conducted numerous lectures and broadcasts for hundreds if not thousands of attorneys in my career.

I do recall Mark Levinstein asking to visit the lab in 2005 for a tutorial on EPO.  At first, I delayed because I was busy and I knew that he also represented Lance Armstrong on some matters.  I asked if this was on behalf of Lance Armstrong or any other athlete.  The answers were ‘no’.  In addition, he added that he knew I had educated groups of attorneys and that was all he was looking for.  Eventually I consented to his visit.

On the appointed day, I introduced Levinstein to my EPO staff, which included Andreas Breidbach.  I did not monitor the conversations.  Although employees are not allowed to discuss cases, it seems from Breidbach’s quotes that he spoke in general of the quality of the testing in the Paris lab.  Obviously, Breidbach did not heed the rules.  As far as I know, no harm came from that incident.  I would not have had any discussions with Levinstein about the case.

I will also point out that during the course of B-confirmations athlete representatives, including attorneys, are allowed to witness the entire testing process.  It was hardly the first time an attorney had been educated on these matters.

Philosophy Behind 2009 Lance Armstrong Monitoring Program:

I was approached to help develop a monitoring program for Lance Armstrong’s comeback in 2009.  As initially conceived, it would have been the first time that any testing organization would be allowed to sample and test Armstrong every three days or even more often and make the analytical data available online for anyone interested to see.  My laboratory would have had unrestricted ability to perform any test we wanted.  Under those circumstances, I did not believe that anybody could get away with cheating.  I was interested to proceed.

Clarification on the intended Armstrong monitoring program:

We were aiming to collect from Armstrong on average every three days throughout the cycling season.  Such a program would be very challenging logistically and would be quite expensive.  It would also likely impact the activities of the international doping control process.  We did not want to impede or interfere with the sanctioning bodies’ ability to test Armstrong, which we knew they would do frequently.

As negotiations were wrapping up, we did perform one collection prior to abandoning the program.  The logistical and cost realities became immediately apparent.  In addition, there were difficulties with the publicity surrounding the program.

The article says that “In its months of overseeing Armstrong’s testing program, Catlin’s lab had collected only one urine sample from him, … and it is clean.”

It is correct that only one sample was collected, however we had only overseen the program for one day, not months.  The results were free of any blood profile abnormalities, the urine was negative for EPO analogues and had a T/E ratio below 4.

References:

While preparing this response I relied on my general knowledge of doping, personal files, specific publications and the following articles:

1) Roberts S and Epstein D.  The Case Against Lance Armstrong.  Sports Illustrated.  January 2011.

2)  Catlin DH, Murray TH.  Performance Enhancing Drugs, Fair Competition, and Olympic Sport.  J American Medical Association 1996;276:231-237. (describes doping control and the system)

3)  Catlin DH, Hatton CK, Starcevic S.  Issues in detecting xenobiotic anabolic steroids and testosterone by analysis of athletes’ urine. Clinical Chemistry 1997;43:1280-1288. http://www.clinchem.org/cgi/reprint/43/7/1280.  (explains the TE ratio in detail)

4)  Catlin DH, Cowan DA, de la Torre R, Donike M, Fraisse D, Oftebro H, Hatton CK, Starcevic B, de la Torre X, Norli H, Geyer H, Walker CJ.  Urinary testosterone (T) to epitestosterone (E) ratios by GC/MS.  I.  Initial comparison of uncorrected T/E in six international laboratories.   J Mass Spectrometry 1996;31:397-402.  (measurement of the TE ratio)

5)  Essay dedication: Coleman DL and Coleman, JE.  The Problem of Doping.  Duke University School of Law.  Duke Law Journal, 2008.

6) Anonymous, Current Biography®, March 2010 issue, 2010. The H.W. Wilson Company (www.hwwilson.com). (Catlin’s career)

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Strict liability rules in doping violations for clenbuterol: the Ovtcharov, Contador and Hardy cases

Clenbuterol

The recent news reported by Associated Press on September 22 that German Olympic Table Tennis medalist Dimitrij Ovtcharov was suspended over a positive doping test was likely missed by many in the United States, but it was certainly not missed in Germany.  What should be notable to all is that this is yet another violation due to clenbuterol, the same drug that Tour De France Champion Alberto Contador tested positive for a few months ago.  Also at the core of this case is the long-held rule of strict liability that has been a core tenet of the anti-doping system and is undergoing a series of tests currently due to the influx of recent clenbuterol positive drug-test reports.

This core tenet, described on page 19 in section 2.1.1 of the World Anti-Doping Code – 2009 says that athletes are responsible for any substance found in their body.  The comment provides a good history of the rule and describes that “in the exceptional circumstance where a Prohibited Substance entered an Athlete’s system through No Fault or Negligence or No Significant Fault or Negligence on the Athlete’s part” modified sanctions may be considered.  The consideration of fault or negligence has been adopted over the course of time based on experiences similar to that of American swimmer Jessica Hardy, who also tested positive for clenbuterol back in 2008 and lost her opportunity to compete in the Olympics because of it.

In her case, our laboratory found that the supplements she was taking were contaminated with clenbuterol.  After a long legal fight, she did receive a reduced sanction of one year based on this consideration, though she has to continue to fight to be allowed to compete in the next Olympic Games as drug test violations in today’s system are supposed to keep you out of the next Olympics.

Apparently as of October 15, 2010 news indicates that Ovtcharov’s doping suspension has been lifted after the report by Cologne doping expert Wilhelm Schaenzer noted that “the intake of clenbuterol through contaminated food was the likeliest explanation for the finding.  A doping related use of clenbuterol is highly unlikely.”

We are not surprised by the notes of our friend and colleague Dr. Schaenzer, as we have had similar musings ourselves in regards to the Contador case.  We do note that nothing in the comments quoted from his report in the article above seem to definitively state where the source of clenbuterol originated.  It is also noteworthy that the Ovtcharov suspension seems to have been lifted after only three weeks based on the statements that he was ‘likely’ not at fault.  Comparing this situation to Jessica Hardy’s one-year sanction and two-year-plus legal battle is perhaps most striking.

Now, we have no inside knowledge or information regarding this matter and we suspect that Dr. Schaenzer would not make such statements without data to demonstrate that the likelihood of doping does not exist in this case.  We would like to find out more information.  We are also curious about the hair test noted in the article, how it was done and what it demonstrated.

Meanwhile we have to wonder about the Contador case as he too has blamed contaminated meat for the clenbuterol finding, according to an article in The New York Times on September 30, 2010.  According to the article, Contador’s hired expert, Dutch scientist Douwe de Boer, “has already generated a paper concluding that ‘it is extremely likely and would be only fair’ to say that the existence of clenbuterol in Contador’s system was from an accidental ingestion of contaminated meat.”  The article goes on to note, “An expert in clenbuterol contamination in meat, however, characterized Contador’s explanation as almost impossible.”  Certainly, the swirling rumors surrounding placticizer tests and blood transfusion possibilities do not help his cause.  Perhaps a hair test will exonerate him as well, we will see.  Meanwhile, Contador must move on to month two of his fight; time will tell if it is as long as Jessica Hardy’s.

Once all is said and done, it will be interesting to examine how the strict liability rules are applied in these cases and the others that are out there.

Contador is not alone; clenbuterol positives are not uncommon

The international sport media has been thrown into a fervor again today over the announcement of Alberto Contador’s positive drug test for clenbuterol.  Unfortunately, he is not alone, as clenbuterol positives have been a recurring problem.  The table below summarizes some of the other cases.  We also highlight some of the things we have learned about clenbuterol and the realities of detecting it through drug tests.

What we have learned:

1) The best way to know if clenbuterol was deliberately used for doping purposes is to evaluate the amount present in the athlete’s urine.

2) Labs can detect minute amounts of clenbuterol on drug tests.  As a result, even very small amounts of contamination in a supplement product can cause a positive drug test.  The Jessica Hardy case is a perfect example.  She was pulled out of the Beijing Olympics at the last minute and was sanctioned because very low levels of clenbuterol were found present in her urine.  Clenbuterol contamination was discovered in a supplement she had been taking.

3) Athletes from China account for the most cases, but Spanish athletes have also been involved.   Twenty years ago there was an epidemic of serious clenbuterol toxicity in Spanish persons – non-athletes.  It was thoroughly investigated and traced to a farm that was using huge doses to bulk up cattle.  Athletes were not involved.   The Spanish authorities responded by establishing new controls, which remain in effect today.

Below is a table of clenbuterol drug test violations as summarized by Zack Bilgake on SportsNickel.com, http://sportsnickel.com/2010/09/30/contadors-clenbuterol-positive-and-what-it-really-means-for-tour-champ/:

ATHLETE NATION SPORT EVENT/DATE OF POSITIVE RESULT OF POSITIVE
Djamolidine Abdoujaparov UZB Cycling 1997 Tour de France/Stage 2 (July 6) Retired
Xiong Guoming CHN Swimming out of competition test in 1999 (March 8 ) 3-year suspension
Wang Wei CHN Swimming out of competition test in 1999 (March 8 ) 3-year suspension
Mariano Puerta ARG Tennis 2003 ATP Viña del Mar (February 12) *ARGUED FOOD CONTAMINATION 9-month susp. + $5600 fine
Zhou Jie CHN Swimming out of competition test in 2005 (Sept 6) *ARGUED FOOD CONTAMINATION 2-year suspension
Karol Beck SVK Tennis 2005 Davis Cup semi v. Argentina (Sept 25) 2-year suspension
Anzhelika Gavrilova KAZ Speed skating positive test before 2006 Olympics (Jan 4) 1-year suspension
Mitchil Mann AUS Weightlifting 2 positive samples in 2006 (Oct 30, Nov 3) 2-year suspension
Ouyang Kunpeng CHN Swimming tested positive before 2008 Olympics (July 1) *ARGUED FOOD CONTAMINATION lifetime ban
Jessica Hardy USA Swimming 2008 U.S. Olympic trials (July 4) *TAINTED NUTRITIONAL SUPPLEMENT/ADVOCARE voluntary Olympic withdrawal/1-year suspension
Reni Maitua AUS Rugby positive test by ASADA (May 20/2009) 2-year suspension
Tong Wen CHN Judo stripped of 2009 world title (May 10/2010) *ARGUED FOOD CONTAMINATION 2-year suspension
Li Fuyu CHN Cycling In-competition test at 2010 Dwars Door Vlaanderen (March 24) 2-year suspension
Callum Priestley GBR Hurdles tested positive February 2010 (Sept 5) *ARGUED FOOD CONTAMINATION 2-year suspension

New Zealand cyclist Adam Stewart banned for two years for attempted use of EPO and hCG

cyclists picture Unfortunately, another story has come out regarding the attempted use of the banned substances EPO and hCG, this time by Adam Stewart, a cyclist from New Zealand. It is attempted use, because the drugs were found during a customs search, not as the result of a positive drug test. On the surface this seems like just another story about doping in cycling, but there are some harsh realities hidden within this story.

The cycling community has done a great deal to clean up the sport by implementing the passport program and taking an aggressive stance on doping as a whole. Some teams even pay for independent testing to add a further layer of protection. Comments by Floyd Landis recently have caused the community to evaluate whether EPO doping is part of the past or whether it continues to be used today. Landis has suggested that it is possible to engage in micro-dosing with EPO combined with traditional blood doping and not test positive in the current drug-testing system. Regardless of what you think about Landis and his allegations, these questions remain as significant concerns and must be answered and evaluated by the scientific community.

What the Adam Stewart situation does answer is a sad but true reality: EPO and its many analogues continue to be sought out and used today by elite cyclists. If Mr. Stewart was caught possessing the drug, one has to think that he had been using it for some time and not testing positive or producing blood values that are suspicious in the passport program. Or, perhaps this is the first time Mr. Stewart got the drug and he had not used it yet? One does have to wonder. If this was not the first time he used the drug then the question needs to be asked, why did he not get caught by the drug-testing system? If he was using EPO and not getting caught then we must look at why and try to address the cause.