FeedNavigator.com caught up with Dr Guy Loneragan, professor of food safety and public health based at Texas Tech University, to hear more about his controversial research, published last week, that found a link between the administration of beta-agonist Zilmax and thousands of cattle deaths in nine feedlots in the US.
Merck, the manufacturer of Zilmax, rejected the findings of Loneragan and his co-authors from Kansas State University, on the basis that the research was ‘observational’.
“Only a well-designed clinical study, in a real world setting coupled with analysis of data by third-party industry experts, can thoroughly confirm the safety profile and performance of a product,” said the drug maker.
Observational studies collect data on events observed in the field, as opposed to randomized clinical trials, which use control groups to study the effects of a product and are thought to be more rigorous.
Data from commercial settings has ‘real value’
But Dr Loneragan, who sits on an advisory board for Elanco Animal Health, said industry should not rush to reject retrospective analysis of data on the use of animal health products in commercial settings:
“It becomes a challenge to carry out a large randomized study in a major feedlot operation and it is also difficult for time-strapped feedlot owners to report back to the sponsor [drug company or additive supplier] data on cattle loss.
While companies like Merck and Elanco take adverse event reporting very seriously and are extremely diligent pharmaceutical companies in this regard, no real mechanism or incentive exists in the post-approval drugs process for users such as feedlot operators to inform a manufacturer that animals fed their product died.
And these owners may not always recognize that the animals' deaths could be linked to Zilmax.
So our observational review of the data, particularly given its large scope, has real value and should not be dismissed.”
Variables taken into account
Death is a rare event in feedlot cattle but increased incidence of mortality across all the feedlots under review had created a suspicion among the owners that Zilmax might be a contributing factor to the excess death loss over 2011 and 2012, said the professor.
Using the appropriate models, said Loneragan, the researchers evaluated pre-screened data captured for them by the owners of the feedlots including information on how long the cattle were at the premises, carcass weight, and the number of treatments per cow.
“We took in as many variables as possible that could confound our observations including the sensitivity of the black hide variety of cattle to heat, given the hot summer in 2012," said Loneragan.
Concerns about Zilmax
The controversial, muscle-building beta-agonist Zilmax, which is fed to cattle during the last few weeks they are in feed yards, was approved by the FDA in 2006, but its safety was called into question in August 2013 after video footage emerged in the US of cattle showing trouble walking and other signs of distress after taking a growth drug.
The supplier halted sales of the drug last summer after Tyson Foods said it would no longer accept Zilmax-fed beef, further raising global concerns about its use.
Compelling evidence
Loneragan and his co-authors found that the data they received provided “compelling evidence” that mortality is increased in response to administration of FDA-approved Zilmax and represents “an unquantified adverse drug event.”
“Measures of effect were relatively consistent across datasets and models in that the cumulative risk and incidence rate of death was 75 to 90% greater in animals administered the βAA [Zilmax] compared to contemporaneous controls.
During the exposure period, 40 to 50% of deaths among groups administered the βAA were attributed to administration of the drug,” found the researchers.
Production efficiencies or animal welfare
“I don’t know what will happen,” said Loneragan when asked about the impact of Merck putting Zilmax back on the market.
He added that if a relationship between Zilmax administration and increased risk of mortality exists, it ought to get industry talking about the pros and cons of the use of drugs approved purely to improve the efficiencies of production yet offering no offsetting health benefits to the animals.
Merck certification process
Merck said last week that “it is too early to say” when it will resume sales of Zilmax in the US and Canada.
The company added that it is continuing its field evaluation program on the feed additive as part of its five-step approach to ensuring responsible beef, and said that to help further ensure safe and effective Zilmax use by customers, a formal certification process has been developed.
“As part of the certification, every feedyard team member, nutritionist and veterinarian who uses Zilmax or provides consultative services on feeding Zilmax to cattle must be trained annually on the proper use of the product,” said Merck.