Several weeks ago we questioned the effectiveness of a National Horsemen's Benevolent and Protective Association call for medication research to be conducted, and possibly adopted, independently of the Racing Medication & Testing Consortium. The HBPA wants the resulting thresholds to be vetted and considered for adoption into the Association of Racing Commissioners International model rules.
The Feb. 9 column elicited comments from HBPA executive director Eric Hamelback, who said too many RMTC thresholds for therapeutic medications are based on estimations and not science. The RMTC disputes this claim, so what's true?
We've jumped into the medication briar patch to sort out the determination of medication thresholds that carry the weight of law. This column is the first of two exploring the RMTC's work and the HBPA's concerns.
The first issues to address are these: Are the thresholds adopted by the RMTC the result of estimates and are they based on legitimate research? "Yes" is the answer to both parts of this question. Already you can feel the briar patch closing in.
Equine research is expensive because horse care is expensive, so there are only a few research herds around the country, ranging from nine to 20 horses. The research conducted on herds of these sizes, however, does produce statistically meaningful thresholds.
Private companies and universities conducting horse research have a goal of producing publishable research. The raw data compiled by these studies can be used to identify therapeutic medication thresholds in Thoroughbred racehorses even though they may have titles like: Detection, pharmacokinetics and cardiac effects following administration of clenbuterol to exercised horse.
"You can count on one hand the number of medications that don't have science behind them," said Dr. Dionne Benson, RMTC executive director. "Many of those are historic levels used prior to the RMTC, like Bute or with topical DMSO."
How are thresholds derived from a study involving between nine and 20 horses? The RMTC uses a statistical approach called 95/95, meaning there is a 95% certainty that 95% of the test results will fall below a given threshold. To get a threshold, the RMTC gets the raw data from a research project, for example, the blood concentration of a medication taken at multiple intervals from pre-administration through 48 hours after the drug was given. Let's say we're looking at results after 48 hours. The numbers are first normalized using logarithms, which accounts for anomalies in the data; then an average is derived. The average is further adjusted to account for sample size and potential errors made during field testing.
For example, let's use an average concentration of 0.43 nanograms per milliliter with one standard deviation from the average at 1.5 ng/ml. The standard deviation would be multiplied by a pre-determined statistical value called the K factor, which prevents a limited set of values from carrying too much weight in a study of limited size. The K factor is 3.032 for nine horses and 2.396 for 20 horses. For a nine-horse study, our standard deviation (1.5) would be multiplied by 3.032 and then added to the average to get the final threshold of 4.97. That number is converted back from a logarithm to a normal number and then evaluated by a panel of practicing veterinarians, researchers, and lab directors.
"We don't make these decisions in a vacuum," said Benson. "I give the Scientific Advisory Committee the highest threshold we have for all forms of administration. The committee will debate whether the drug at that level could influence performance and whether it could affect the outcome of a race.
"The committee is always conservative and always rounds up," she continued. "There are plenty of people who believe we are too liberal."
The HBPA and the North American Association of Racetrack Veterinarians are decidedly not in the liberal camp. Their concerns include thresholds set far below levels where drugs have a pharmacological effect, thresholds based on thin research, and a heavy reliance on controlled studies with little consideration of real world applications.
A recent threshold change for xylazine (a muscle relaxant and sedative) from 10 pg/ml to 200 pg/ml is a good example, according to Dr. Clara Fenger, a practicing vet, former researcher at University of Kentucky's Gluck Center, and a member of NAARV.
"It's great they raised the threshold, but what about all the horsemen who got caught when it was 10 pg/ml?" she said. "They need to do the good studies first before publishing a threshold. And we can't have thresholds so low that a horse can accidentally trigger its own positive by eating contaminated bedding or hay. You want to go after dermorphin? Absolutely. Cobra venom? EPO? Go for it, but therapeutics? It makes no sense when 95 picograms is nothing...95 grains of red sand on a beach."
Regarding the xylazine change, Benson said all thresholds are dynamic and subject to change with new research. The new threshold also included a recommended dosage, which had not been offered before.
Next week we'll explore the HBPA and NAARV's proposal to conduct its own medication field studies.