Complex study design and intense marketing make evaluation difficult
Editor’s note: This is the third in a series of articles on mastitis, treatment protocols and new research.
The onslaught of new research findings for medications and vaccines, often then accompanied by advertising supporting new claims, makes it difficult to know if the products will work in your herd.
For a dairy farmer—and even the herd’s veterinarian— interpreting complex new research is often extremely difficult, says Pat Gorden, a veterinarian and director of food supply veterinary medicine at Iowa State University.
He knows how difficult interpreting results can be since he also heads up mastitis control and treatment efforts for Iowa State’s 400-cow university herd. And he has spent seven years as a large herd veterinarian in the Southwest before joining Iowa State.
“By themselves, farmers are probably not able to evaluate a lot of these claims,” he says. “The same can be said for many veterinarians. Research trial design and statistics is not heavily incorporated into veterinary training.”
Most farmers, Gorden says, will rely on their veterinarians to sort out the claims. And many veterinarians need to speak to Extension and university experts who understand the statistics and are independent from the research to get a good perspective of the data.
If a farmer and veterinarian decide to make a change based on the new research, it is difficult to know if the change works. “Changes in weather, feed, employees and other factors may far outweigh the ability to determine if a change in treatment outcomes is occurring,” says Gorden.
“So you have to go back to what the research is telling us and what the cost effectiveness of the treatment is based on that research,” he says.
Two recent examples of new research illustrate Gorden’s point. In the first example, Cornell University completed a mastitis treatment study comparing two doses of ToDAY versus five doses of Spectramast. The study, using seven commercial dairy herds, was funded by Boehringer Ingelheim, makers of ToDAY.
The first complication was that the study was a “non-inferiority” trial. Non-inferiority experiments are done to compare a new or alternative treatment to an industry standard.
In the Cornell study, the non-inferiority experiments were done to compare whether a newer generation drug, in this case Spectramast LC, was superior to an older drug, ToDAY.
The threshold was set at 15% because of the higher treatment and milk withholding costs associated with Spectramast LC. In other words, Spectramast LC had to be at least 15% better than ToDAY for Spectramast LC to be judged superior.
The results of the trial showed that Spectramast was 12% better than ToDAY overall, but it did not reach statistical significance. Digging deeper though, the results showed no difference in cures of gram-positive organisms between the treatments. But Spectramast was clearly better for gram negatives, Gorden says.
What to do? “If I don’t culture or know what is causing the mastitis, I would use Spectramast,” says Gorden. Why? You get equal effectiveness against gram positives and better results against gram negatives.
The decision matrix changes, however, if you culture and know whether gram-positive or gram-negative bacteria are causing mastitis. The decision then comes down to treatment cost and residue risk, Gorden says. The Cornell trial compared two treatments of ToDAY 12 hours apart to five daily treatments of Spectramast. The withdrawal period of ToDAY is 96 hours. Spectramast withdrawal is 72 hours.
Based on the study’s protocol, ToDAY might be the preferred treatment option because of lower drug costs and a total milk withhold of five days versus eight days of total milk withhold with Sectramast.
Zoetis veterinarians have complained that the Cornell trial should have compared two treatments of
ToDAY to two treatments of Spectramast. (The Spectramast label allows treating two to eight days.)
But the study didn’t do that. So you don’t know if the cure rate with two tubes of Spectramast is equal to two tubes of ToDAY, says Gorden.
“That’s why you have to have your veterinarian in the middle of all of this,” he says.
The second decision is whether to treat gram negatives. At the Iowa State herd, Gorden rarely if ever treats gram negative mastitis because the infection is usually transient. “But if I were going to treat all gram negatives, this data supports using Spectramast,” Gorden says.
A second example of complex research was done at the University of Wisconsin, looking at the metabolites of the active drugs in ToDAY and Spectramast. This study was also funded by Boehringer Ingelheim.
The underlying biology is that when an antibiotic is injected into an animal, it is metabolized and converted into new compounds. How quickly it metabolizes and whether the resulting metabolites have effective bacteria killing power is critical to the drug’s effectiveness.
The Wisconsin study looked at how quickly both ToDAY and Spectramast converted to their metabolites in the lab. Spectramast had almost complete conversion to its metabolite while ToDAY did not.
At first reading, Gorden says it appeared to him that ToDAY would be more effectivethan Spectramast. But then he checked with his colleague who has a doctorate in pharmacology.
His colleague pointed out that Spectramast metabolism is very different, depending on whether it is injected into tissue, blood or milk. Other research shows Spectramast maintains its bacteria-killing power between doses when injected into the udder, says Gorden.
As previous articles in this series show, it is critically important to culture mastitis and then only use products effective against the cultured organism.