Dear Mr. Murray,
This response is to address your comments and concerns about
the wording of statements added to the "Post Approval Experience"
section of the Deramaxx label. Your concerns appear to be based
on your interpretation of the Adverse Drug Events (ADE) data associated
with the product.
The purpose of the Center for Veterinary Medicine's (CVM) monitoring
system is not to collect statistics. Rather, the system is designed
to look for drug side effects and other adverse drug events that
are not presently reported on products' labels, and to advise
veterinary practitioners of the benefits and risks of animal drug
products. Each reported reaction is evaluated and scored. It is
the collection of reactions, judged for severity and frequency,
that drives label changes. This is a regulatory process that is
performed separately from and independently of the drug company.
The ADE data published on the Center for Veterinary Medicine's
(CVM) website provides the public, including veterinary practitioners,
with meaningful risk information thereby contributing to animal
health and safety. The ADE-related pages on CVM's website (e.g.
http://www.fda.gov/cvm/index/ade/ADEReport.htm ) also include
substantial information to aid readers in interpreting the data
as follows:
1. http://www.fda.gov/cvm/index/ade/ADEReport.htm
These reports include all domestic adverse drug experience reports
submitted to the Center for Veterinary Medicine (CVM or the Center)
that the Center has determined to be at least "possibly"
drug related. The Center's adverse drug experience (ADE) process
takes into consideration confounding factors such as:
· Dosage
· Concomitant drug use
· The medical and physical condition of animals at the
time of treatment
· Environmental and management information
· Product defects
· Extra-label-uses
However, the specifics of these complex factors cannot be addressed
in these reports.
NOTE: These reports are intended ONLY as a general reference
to the type of adverse experience that veterinarians, animal owners,
and others have voluntarily reported either to the FDA or to the
manufacturer as associated with drug use. These reports should
NOT be used for:
· Determining drug association for a particular sign
· Determining the safety and efficacy of a given drug
· Determining the frequency of occurrence of an adverse
experience
· Determining the effects of on-label versus extra-label
use of a drug
· Comparing one drug with another drug
2. http://www.fda.gov/cvm/index/ade/ade_description.htm
The primary purpose for maintaining the FDA/CVM DAE database
is to provide an early warning or signaling system for adverse
effects not detected during premarket testing of FDA-approved
animal drugs and for monitoring the performance of drugs not approved
for use in animals. The FDA/CVM ADE reporting system depends upon
the detection of an adverse clinical event by veterinarians and
animal owners, the attribution of the clinical event to the use
of a particular drug ("suspect" drug), and the reporting
of the ADE to the manufacturer of the suspected drug or directly
to FDA. Data from these ADE reports are coded and entered into
the computerized FDA/CVM ADE database.
It is important to remember certain caveats when using data from
the FDA/CVM ADE database as follows:
1. For any given ADE report, there is no certainty that the suspected
drug caused the adverse event. This is because veterinarians and
animal owners are encouraged to report all suspected ADEs, not
just those that are already known to be caused by the drug. The
adverse event may have been related primarily to an underlying
disease for which the drug was given, to other concomitant drugs,
or may have occurred by chance at the same time the suspect drug
was administered.
2. Accumulated ADE reports should not be used to calculate incidence
rates or estimates of drug risk.
Based upon your comments it appears your estimate of the incidence
(21%) is a misinterpretation of the ADE data posted on CVM's website
and a gross overestimation of the incidence of death as an adverse
event related to the use of Deramaxx. Due to case-specific variables
such as concomitant drugs, pre-existing medical problems, patient
age, and others, we cannot always be certain that there is a direct
correlation between a specific adverse reaction and the particular
drug implicated in causing the reaction. All factors must be taken
into account.
The NSAIDs as a class of drugs carry risks. The FDA approves
them with labeled information regarding recommendations for owners
to observe for side effects so that early intervention and timely
treatment can take place. The FDA also approves them with recommendations
for pre and post-administration monitoring of blood work in much
the same way the FDA makes recommendations about any other drug
that requires monitoring. This is not unique to animal drugs;
it is also very common with human NSAIDS, "statins"
and other drugs that carry some risk.
Marcia K. Larkins D.V.M.
Ombudsman
Center for Veterinary Medicine
