By Tom Polansek and P.J. Huffstutter
(Reuters) - The number of U.S. cattle deaths that may be linked to the Merck & Co Inc feed additive Zilmax are much higher than the figures reported by the drug company to the federal government, according to a research study published on Wednesday.
The findings by researchers from Texas Tech University and Kansas State University show that more than 3,800 cattle in 10 feedlots that were fed Zilmax died in 2011 and 2012, with between 40 percent and 50 percent of the deaths likely attributable to Zilmax.
The numbers reported in the study, which was published in the scientific journal PLOS ONE, would indicate a larger death toll than Reuters found late last year in a review of all deaths reported to the U.S. Food and Drug Administration by Merck since Zilmax was introduced in 2007. Drug makers are required to report deaths and other adverse events associated with their drugs - in this case based largely on what cattle and feedlot owners have told the company.
The Reuters review of federal records showed Merck reported 285 cattle had died unexpectedly or were destroyed in the United States after being fed Zilmax during the six years of Zilmax sales in the U.S.
Merck said it was confident in the "safety and performance" of Zilmax and criticized the methods used in the study.
The findings were "based on observational information and we disagree with them," the company said in a statement.
"Using observational analyses where cattle are not randomized and where rigorous scientific procedures are not utilized, is not a respected scientific method to rigorously evaluate the safety and efficacy of any product," Merck said.
The study could add to concerns about the safety of the drug, which has not been available in the U.S. and Canada since Merck last August temporarily suspended sales after reports of cattle suffering lameness and mobility problems.
It could also fuel debate about whether there is enough regulatory oversight of feed supplements made from a class of drugs called beta-agonists.
The FDA said it will review the new research data and add them to the agency's body of knowledge regarding Zilmax. The agency, which has deemed both drugs safe for animals and humans,
can ask drug companies to make changes to product labels if it detects safety concerns.
The beef industry has used Zilmax and other beta-agonist drugs to bolster its bottom line for nearly a decade by creating heavier cattle. Zilmax can add up to 30 pounds of meat to a 1,300-pound market steer.
Feedlots provided the data on cattle that were fed with Zilmax to the researchers and asked them to analyze it.
The largest population of cattle reviewed by the researchers was a grouping of 722,704 animals in 2011-12 from nine different U.S. feedlots. Of 637,339 that were fed Zilmax, 0.53 percent died prior to slaughter, according to the report. That is well above a 0.3 percent death rate among the 85,365 cattle that were fed neither Zilmax nor a rival beta-agonist, Optaflexx.
A separate study of 149,636 cattle from one feedlot in those same years showed that 83,865 animals fed Zilmax had a 0.48 percent chance of dying before going to the slaughterhouse, according to the report. That compares to a 0.26 percent death rate among the 65,771 cattle that were fed neither drug.
The researchers reported that cattle fed with Eli Lilly & Co's Optaflexx showed a mortality rate of 0.35 percent among 39,890 cattle. That compares to a 0.18 percent death rate among 39,281 cattle fed neither drug. The Optaflexx data was based on animals at four cattle-feeding companies a few years earlier.
Both drugs "are most likely causally associated with increased cumulative incidence, incidence rate, and hazard of death when they are administered in accordance with the FDA-approved label directions," the study said.
However, the researchers did warn that it is difficult to definitively establish a causal relationship between Zilmax and increased mortality because of the "observational nature" of the data. The study of Optaflexx use was not specifically focused on animal mortality, the researchers noted.
Observational studies collect data on events observed in the field, as compared to randomized clinical trials, which use control groups to study the effects of a drug and are generally regarded as more rigorous.
"We do not believe the data is causally associated," Lilly's Elanco Animal Health unit said in a statement.
One factor that elevated the mortality of the group of cattle fed Optaflexx was the number of times the cattle were fed per day, Elanco said. But after adjustments to the feeding schedules the problem was eliminated, the company said.
Guy Loneragan, an author of the report and a food safety professor at Texas Tech, sits on an advisory board for Elanco, which provided seed funding for the study.
Merck is working to reintroduce Zilmax in the U.S. and Canada, but meat packers and others have been reluctant to resume using it.
Ty Lawrence, an associate professor of animal science at West Texas A&M University and a consultant for Merck, said at an industry meeting in Texas last month that data from controlled studies supported drug company claims that beta-agonists are safe.
Loneragan told Reuters that Merck may not reliably receive Zilmax-related death reports from its customers, who fatten up cattle prior to slaughter, because the feeders may not always recognize that the animals' deaths may be related to Zilmax.
"It's taken a huge amount of observation to start to piece together some of these side effects, or adverse drug events if you will," he said.
(Reporting by Tom Polansek and P.J. Huffstutter; editing by David Greising and Martin Howell)