Drug Testing Under HISA: When Uniformity and Variability Collide

From an altitude of 10,000 feet, the Horseracing Integrity and Safety Act (HISA)'s mandated goal is a simple two-pronged affair. Uniformity in welfare and safety. Uniformity in drug testing.

Over the past few months, the Horseracing Integrity and Welfare Unit (HIWU)–HISA's enforcement arm–has made several announcements that have peeled the curtain back on just how difficult the second part of that equation will be to accomplish.

Internal reviews of the six HIWU-contracted laboratories uncovered different limits of detection in blood for diabetes drug Metformin and for benzoylecgonine (BZE), a metabolite of cocaine. In the case of Metformin, all the positives originated from just the one lab.

After dropping several cases against trainers for Metformin and BZE positives, HIWU explained that it had subsequently harmonized its “testing sensitivity” in blood across the six labs for these two substances, and that it would repeat the harmonization process for other drugs, including banned substances of which there are listed well over a thousand.

“There are an awful lot of substances out there that we need to sort through, and we won't sort through them until they're actually identified by a laboratory,” said HIWU chief of science, Mary Scollay, at a recent HISA town hall. “But we are committed to harmonizing across laboratories in fairness to stakeholders.”

Scollay then added this coda: “It's important to realize that the lack of harmonization across laboratories has existed for decades.”

For those who have watched drug testing evolve in the sport over the years, Scollay's words hardly came as a shot from the dark. One of the key drivers of federal regulation of horse racing was to eliminate the crap-shoot nature of drug testing under a state-by-state system.

But under HISA, why haven't these differences been ironed out?

The answer involves a bracing plunge into the opaque waters of drug testing, where clear answers can be as easy to retrieve as Excalibur from its stone, and where arcane terminology is used interchangeably depending upon the person talking.

But it turns out that a variety of issues–from different testing equipment to different testing methodologies to different sets of staff interpreting the results–have all played a part in leading the sport to where it finds itself now.

HIWU has “testing specifications” for more than 300 “core” analytes–most of them controlled medications but some banned substances–to which all HIWU-contracted laboratories are required to test.

“Beyond those analytes, HIWU has asked each laboratory to utilize the broadest scope of analysis available to them,” wrote Scollay, in response to a list of questions.

Outside of those 300 or so core analytes, therefore, testing variability from facility to facility means the six HIWU-contracted labs are screening for different numbers of substances, and have varying abilities to screen for the same substances, according to drug testing experts. In other words, the same sample sent to two different laboratories could result in two different sets of results.

Furthermore, as HIWU–which was built by Drug Free Sports International–continues to work through a laborious “lab harmonization” process, what are the implications for the horsemen and women facing potentially life-changing sanctions for banned substance violations? And how can stakeholders be assured that newly established harmonized limits adequately factor in the risk of inadvertent contamination, especially those banned substances ubiquitously used by humans?

“It would be one thing if this was just a fine and a ten-days [ban],” said Cynthia Cole, former director of the University of Florida's (UF) laboratory. No contractual agreement was reached between the UF lab and HISA. In different equine anti-doping cases, Cole has both provided testimony for HIWU, and prepared opinions for trainers defending themselves.

“But these bans, these are career ending for people,” Cole added. “I just feel really strongly that the bar should be very high, and that there should be no doubt that there was a violation.”

History

“Incredulity and disbelief ran neck and neck, but outrage outstripped them both at Santa Anita Saturday as horsemen reacted angrily to the latest drug scandal to rock thoroughbred racing.”

The above paragraph, which reads as though plucked from a story from recent years, instead originates from a 1989 LA Times article, when a spate of cocaine positives had entangled several trainers, including leading lights like Wayne Lukas and Laz Barrera.

The reason given for the sudden rash of cocaine positives? That Truesdail Laboratories, the drug testing laboratory used at the time by the California Horse Racing Board (CHRB), had started to use more sophisticated equipment to analyze the samples.

According to one official at the time, the “improvements in testing” had suddenly increased the sensitivity of the equipment “10-fold.”

In other words, new state-of-the-art instruments were detecting substances in blood and urine at previously unachievable levels. Some said at the time the levels were so small as to be inconsequential–a refrain that has turned into a steady drumbeat in the intervening years.

“The increased sensitivity in drug testing has resulted in a number of things being called positives that never would have been called before,” said Eric Hamelback, chief executive officer of the National Horsemen's Benevolent and Protective Association, speaking at the 2019 National HBPA Convention.

The same drumbeat has reverberated around other equine sports, as well.

Nearly 20 years ago, one Irish veterinarian who had administered a “mild sedative” to the high-level show jumper, Landliebe, one-month prior to a failed drug test subsequently issued a public statement evoking “amazement” that traces of the drug could still be found in a horse's system after that time.

On a practical front, drug testing has evolved in an attempt to keep up with an ever more sophisticated array of performance enhancing drugs and doping methods. In human sports at least, regulators don't appear to be winning that war, for there remains quite a lag-time between new drugs coming onto the scene and reliable ways to test for them.

But advances in testing sensitivity has also had the effect of widening the gap between possibility and practice from one lab to the next. For it turns out there exists a complicated set of issues that weigh into testing variability between facilities.

The instruments used to analyze samples, the way tests are prepared for sampling, the types of tests run, the substances being tested for, staffing expertise, ongoing research into the detection of emerging substances and a slew of other issues all play a part.

Just Why Are Labs Different?

In pre-HISA days, individual state commissions contracted their drug testing programs out to individual laboratories. And though most states followed the Association of Racing Commissioners International's (ARCI) model rules, it still left a lot of contractual wriggle room around things like the scope and type of testing performed, what specific matrices–blood or urine, for example–were being tested, and so on.

At the end of the day, however, the relative accuracy and breadth of each drug testing program can–like so many things in life–be distilled down to money. Funding for the drug testing program, for one. And funding to keep the laboratories at the cutting edge of science.

“In a lot of cases, the determining factor in those contracts was price, with the low bidder winning the work,” said Richard Sams, an expert in racing chemistry and toxicology. Sams is also a former lab director currently advising several defendants in cases against HIWU.

“Low-bidding often meant limited testing, and oftentimes, not very high quality testing,” Sams added.

Take Joe Gorajec's term as executive director of the Indiana Horse Racing Commission. Back in 2015, he organized for blood samples taken from harness and Quarter horses to be sent to the California-based Truesdail Laboratory–the Commission's official lab at the time-and to two audit laboratories: LGC in Kentucky, and Industrial Laboratories in Colorado.

Gorajec's actions led to the Indiana racing commission severing ties with Truesdail after it failed to detect in three samples high levels of commonly used corticosteroids that the other two laboratories detected.

Under HISA, of course, the regulatory dynamic in drug testing has changed. But horse racing has swapped out a patchwork quilt of different rules for a patchwork quilt of different labs.

Though a single entity now contracts out a set of testing requirements to six different laboratories, the fact that no two labs are created equal remains a thorn in the side of testing uniformity. And experts single out two primary reasons why.

One concerns the instruments used to analyze the samples. In a recent presentation at the Global Symposium on Racing in Arizona, Scollay compared the situation to the use of different ovens from kitchen to kitchen.

This is where the specter of poor funding continues to loom large. “Some of the laboratories have brand new instruments–state of the art,” said Cole. “Other laboratories, not so much.”

Historically well-funded laboratories like UC Davis's “Maddy Lab” in California and the University of Kentucky's Equine Analytical Chemistry Laboratory have “a lot of new equipment and a lot of very well-trained chemists and technicians,” said Cole.

When it comes to HIWU-contracted laboratories like the Ohio Department of Agriculture's Analytical Toxicology Laboratory, and the Animal Forensic Toxicology Laboratory at the University of Illinois-Chicago, “these are smaller laboratories with generally older equipment,” Cole said.

“Over the years, they've adapted to what they've been asked to do, and they've developed their own methods of testing and confirmation methods, and they're not the same,” said Cole.

To get a gauge on just how crucial funding can be, a top-of-range liquid chromatography-mass spectrometry system can retail around the $750k mark. And these machines can have a shelf-life of only around a decade, give or take a few years, due to ongoing technological advances.

The other key area concerns drug testing extraction methods. This is the process by which the substance or analyte is removed from the blood or urine to be examined under an instrument like a mass spectrometer.

There are all sorts of different extraction processes for different analytes, and each of these processes can be “substantially different” depending on the lab, Sams said.

“The fraction of the drug that's present in the sample that gets removed by the process can vary considerably from one lab to the next,” said Sams.

Horse racing is far from the only sport confronting these sorts of problems. Just take this 2022 paper, in which three Norwegian researchers focus on the World Anti-Doping Agency (WADA)'s approach to drug testing in human athletics.

“Some laboratories are capable of detecting lower concentrations of prohibited substances than other laboratories, simply because the laboratories may use different equipment and/or test methods,” the researchers write.

HIWU'S Approach

If lab variability has been a decades-long problem ensnaring all professional sports, not just horse racing, why has it become a lightning rod under HISA?

One of HISA's most compelling selling points has been the advent of a level playing field comprising the same drug testing rules and a stable of accredited laboratories “testing for the same banned and controlled medicines at the same level,” as HISA CEO, Lisa Lazarus, put it in September of this year.

But for the reasons already identified, the goal of a completely fair drug testing playing field for all participants–no matter their location in the country and no matter where a sample is sent-is a major challenge when dealing with multiple laboratories.

The more labs needing to be unified in their capabilities, equipment and approaches, the more complex and expensive the problem.

For U.S. horse racing, the crux of this issue primarily surrounds HISA's lengthy list of banned substances–those substances, in other words, beyond the more than 300 core analytes that HIWU's six labs can test for reliably.

Banned substances are not supposed to be detected in a horse's system at any point, racing or training. As such, violations for these substances come with the heaviest penalties under HISA, including a potential two-year ban for the trainer. No trifling matter, therefore.

Unlike most controlled substances under HISA–those with set thresholds and screening limits–banned substances under HISA are being tested to limits of detection, which is the lowest concentration of a substance that can be identified by a laboratory. And different labs can have different limits of detection for the same substances. That's if they're testing for them at all.

As Cole puts it, “I think the really difficult issue has come up with the banned substances, which is where they basically have said, 'if it's there at all, it should be called.' That's been a problem because you can have a laboratory that's very, very good at finding [a banned substance], and then another lab where their ability to detect [a banned substance] isn't as good.”

When asked about this aspect of the drug testing program, Lazarus wrote in emailed answers to questions that “it is important to remember that all samples at any given racetrack go to the same Laboratory,” so lab variability is not a problem within the same “races and meets.”

It's unclear just how many banned substances for which HIWU has set harmonized limits of detection. Nor will the specific limits be made public, once established.

“HISA/HIWU cannot comment on the number of Banned Substances that have a harmonized Limit of Detection,” wrote Scollay. “Since Banned Substances should never be in a horse, laboratory testing specifications for them are not published.”

Another key question is this: Exactly how many substances is each lab routinely screening for?

According to one state regulator–who asked to remain anonymous–the most proficient HIWU-contracted laboratories are screening for around double the number of substances as some other HIWU-contracted labs.

Scollay didn't deny the claim, but explained how beyond the more than the 300 “core” analytes, “HIWU cannot speak to the overall capabilities of each lab.” She added, however, that a key part of the harmonization process is the “collaboration and sharing of information” between labs.

Human Drugs

Which leads to the issue of those banned substances which are commonly found in everyday life, like legitimately prescribed human drugs.

What process is the agency using to ensure that the harmonized limits of detection weigh the possibility of intentional misuse of a banned drug in a racehorse against the threat of inadvertent contamination?

In her written responses, Scollay explained that the agency uses any or all of the following criteria to set “relevant, effective, and achievable” harmonized limits of detection in banned drugs:

Dr. Mary Scollay | The Jockey Club

1–A survey of the laboratories to determine their current capabilities to detect the substance.

2–Conducting a review of the science surrounding the substance to determine illicit use in human and equine sports, or its effects in other mammalian species.

3–Assessing the threat level of the substance. “I.e., the potential for that substance to be present in the horse's environment beyond the control of the trainer,” Scollay wrote.

Scollay wrote that HISA and HIWU also consult the international community on testing specifications, “and consider their controls on Banned Substances and Controlled Medications that are not regulated by Screening Limits or Thresholds.”

A feature of the new regulatory environment is the potential for trainers to be provisionally suspended for banned drug positives while they await a hearing.

In Jonathon Wong's case, for example, the trainer has been provisionally suspended for at least 170 days for a June 1 Metformin positive.

What happens if one of the six HIWU-contracted labs detects a new banned substance without a harmonized limit of detection? How will the cases be handled while the harmonization process takes place?

“The actions taken will depend on the specific circumstances of the case with an emphasis on fairness to all racing participants,” wrote Scollay.

International Community

International regulators like the British Horseracing Authority avoid the issue of lab variability by using only using one primary facility to test their samples in their jurisdiction.

But how do other international jurisdictions handle substances with no established international threshold, residue or screening limits?

In Europe, at least, the answer sounds familiar.

The European Horserace Scientific Liaison Committee (EHSLC) considers some substances to be prohibited-at-all-times, as is the case with anabolic steroids and other anabolic agents. For these substances, European laboratories generally work to the lowest concentrations their confirmatory analysis procedures allow.

But the EHSLC also maintains an evolving list of substances that have “target sensitivities”–in other words, agreed-upon screening concentrations similar in effect to HIWU's “harmonized limits of detection,” said Clive Pearce, an internationally renowned animal sports medication and doping control expert.

To generate this list, the EHSLC's veterinarians, analytical chemists, pharmacologists, and racing administrators work together to select substances whose presence in a racehorse's blood or urine sample would be of particular concern.

What are these concerns? That such substances are, for example, unlicensed veterinary products, routinely used human medicines, or environmental and plant-based contaminants, Pearce explained.

The “sensitivities” agreed upon for each substance reflect the concentrations considered to have the potential to affect a racehorse's performance or to compromise its welfare.

More broadly, for all substances subject to the EHSLC's process for achieving drug screening harmonization, the most important consideration is that all its laboratories are able to routinely deliver the same level of detection, said Pearce.

According to Pearce, the list of substances with “target sensitivities”–drug substances and their major metabolites in both blood plasma and urine–total about 150.

At the symposium in Arizona, Scollay explained that there are now new “open lines of communication” between HIWU and the EHSLC.

Why can't the EHSLC simply share all relevant information on substances with “target sensitivities” with HIWU, therefore? It turns out it's not that simple.

“The international community's research and laboratory testing specifications are confidential,” Scollay wrote. “International jurisdictions limit their information dissemination due to potentially compromising their own anti-doping and medication control programs.”

Other experts consulted for this story were more specific. They explained that the litigious nature of U.S. horse racing can make international jurisdictions wary of sharing with their American counterparts sensitive information that might be publicly divulged during a case.

If all boats can't be lifted by readily shared information across international borders, how else then to make the program here better, quicker?

Solutions

Gorajec is all in on federal oversight of racing. He played an instrumental part in getting HISA passed in Washington. But he said he has his reservations about the current drug testing program.

“This shouldn't be an issue at this juncture,” said Gorajec, highlighting the documented problems associated with uniformly detecting BZE, the cocaine metabolite long on regulators' radars. “They had a couple, three years to get their arms around this. Cocaine has been around for decades.”

HIWU-contracted labs must be accredited with an international standards organization and with the Racing Medication and Testing Consortium (RMTC), the latter of which handles an external quality assurance program, which includes single- and double-blind testing of the six labs.

HIWU officials are also putting together another accreditation program to “build on the foundations” of the international and RMTC accreditation systems as the agency “moves testing laboratories towards harmonization of methodologies and sensitivities across the spectrum of Prohibited Substances.”

What would help, Gorajec said, would be to significantly raise accreditation standards to whittle down the number of HIWU-contracted labs to just the most proficient. “That should have already been done,” he said.

When asked about Gorajec's comments, Lazarus wrote that HIWU will evaluate the contracted laboratories on a regular basis, “and if a Laboratory does not meet HIWU's performance criteria, it will not be continued in the program.”

Cole suggested for HIWU to establish an oversight committee-possibly populated by a chemist, a veterinary pharmacologist and an industry figure-to review new or unusual findings and make recommendations as to whether they should be pursued.

“They are trying to fix the plane while it is in the air,” said Cole, about the work HIWU officials are doing to fix the problem of lab variability. “But they are trying.”

According to Ed Martin, president of the Association of Racing Commissioners International (ARCI)–another key industry figure not shy of voicing his concerns and frustrations with the federal law–HIWU should convene a long meeting between the various lab directors with the sole purpose of reaching an agreement as to what the “point of regulatory action” is on a list of some of the more commonly called substances.

“It would seem to me, the best way to insulate themselves from legal challenges would be to get that done sooner rather than later,” Martin added.

In response to Martin's suggestion, Scollay wrote that HIWU conducts weekly meetings with the directors of its contracted laboratories.

“There have been multiple discussions regarding strategies to achieve harmonization,” she wrote. “All the directors are committed to this goal, but all parties recognize that time is needed to reach it. In short, meetings are already happening on a weekly basis.”

When asked about her overall thoughts as to the harmonization process, Lazarus wrote that she was “absolutely thrilled” at the progress made in the time given.

“The discrepancies amongst states under the prior system were significant, so to be where we are at such an early stage is a major benefit to the industry,” wrote Lazarus. “I am also proud of the transparency and adjustments HIWU has made when a non-harmonized analyte is identified. These adjustments have all been to the benefit of horsemen. Prior to HISA, this level of transparency did not exist at the Laboratory level.”

As racing continues to grapple with the practical and legal conundrums posed by lab variability, stakeholders can seek cold comfort from the fact they are not alone.

The Norwegian researchers critical of WADA's drug testing program zero in on the testing of “so-called non-threshold substances” for accusations of subjectivity.  “These tests lack objective and quantifiable decision limits that undisputedly resolve whether test results should be interpreted as positive or negative,” they write.

The lack of “clearly defined criteria for doping tests,” the researchers added, “carries a great risk of punishing innocent athletes and undermines the fight against doping in international sports.”

Sound familiar?