FDA/CVM 1997 ADE REPORTS -- A DESCRIPTIVE OVERVIEW

By Neal Bataller, ME, D.V.M.
FDA Veterinarian Newsletter January/February 1999 Volume XIV, No I

I. Introduction

This article presents a descriptive overview of the 4,738 evaluable, postmarket adverse drug experience (ADE) reports received by the U.S. Food and Drug Administration, Center for Veterinary Medicine (FDA/CVM) during calendar year 1997. An ADE report consists of either an undesired side effect, or the lack of a desired effect associated with drugs administered to animal(s). Reports may also involve potential harm posed to persons administering or using animal drugs.

In previous years, a summary of these ADE reports was included as an insert in the FDA Veterinarian. This summary was not included in the newsletter this year because of its length. However, copies of the 1997 Veterinary Adverse Drug Experience (ADE) Summary may be obtained from CVM's Internet Home Page or by calling or writing the FDA Veterinarian.

The primary purpose for maintaining the FDA/CVM database is for providing an early warning or signaling system for adverse effects not detected during premarket testing of FDA-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.

The reporting of ADEs by veterinarians and animal owners is voluntary. They may send their reports directly to the FDA/CVM ("Direct" reports), to the drug manufacturer ("Manufacturer" reports), or both. The drug manufacturers of FDA-approved animal drugs are required by law and regulation to submit to the FDA postmarket ADE reports received by any means from veterinarians and animal owners.

It is important to remember certain caveats when using data from the FDA/CVM ADE database:

1. For any given ADE report, there is no certainty that the suspected drug caused the ADE. 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.

In this article, various kinds of data and information are presented on the ADE reports computerized into the FDA/CVM ADE database during the calendar year 1997. Due to rounding, the percentages in tables may not total to 100 percent.

II. Report Submission Information

Table 1 shows the number of reports received for the last six full calendar years. The numbers only include original reports involving animal injury; follow-up reports and product defect reports are not included. In general, the annual number of reports has increased, although much of the increase in the latter years is attributable to a few newly approved animal drugs.

Table 1. ADE Reports by Year

Year Number

1992 1,011

1993 1,250

1994 1,746

1995 3,193

1996 3,112

1997 4,738

While ADE reports are submitted to CVM from a variety of sources, the bulk of reports are received by the sponsors of FDA-approved animals. As mentioned above, drug sponsors are required by law and regulation to submit all reports involving animal injury, product ineffectiveness, and product defects. Drug manufacturers of human drugs or unapproved animal drugs are not required to submit any ADE reports to CVM, so very few ADE reports are submitted to CVM for these types of drug products.

TABLE 2. 1997 ADE Reports Ranked by Source (N=4,738)

III. Animal Zoographic Information

Table 3 lists the species that are most represented in ADE reports. The majority of reports involve companion animals and cattle. Few reports are received that involve poultry. The average number of animals adversely affected in each report is more reflective of the animal management and health care associated with each species.

Table 3. 1997 ADE Reports by Species, Plus Average Number of Animals Adversely Affected Per Report (n=4,738)

IV. Suspect Drug Information

The remaining tables in this article only involve reports that the Center has determined to be at least "possibly" drug-related. A number of different factors are considered in determining this classification. The tables in this section describe the drugs involved in these reports with the data organized by (1) general drug class; (2) active ingredient(s); and (3) product tradename.

Table 4. 1997 "Possible" ADE Animal Injury Reports by Top-10 Ranked of Suspect Drugs (n=3,817)

Table 5. 1997 "Possible" ADE Animal Injury Reports Listed by Top-10 Ranked Active Ingredients of Suspect Drugs (n=3,817)

Table 6. 1997 "Possible" ADE Animal Injury Reports Listed by Top-10 Ranked Names of Suspect Products (n=3,817)

V. Drug Usage Information

Table 7 lists the route of drug administration most commonly represented in ADE reports. Note that the oral category generally represents tablets, capsules, powders and pastes while the medicated feeds involve the consumption of animal feeds containing drugs.

Table 7. 1997 "Possible" ADE Animal Injury Reports Ranked by Top-10 Ranked Routes of Drug Administration (n=3,817)

VI. Adverse Event Information

Table 8 lists the most common adverse clinical manifestations contained in ADE reports considered as at least "possibly" drug-related. Again, care should be taken in interpreting this ranking since many factors affect whether a veterinarian or animal owner is motivated to actually report an adverse drug experience. The seriousness of an adverse event may affect the likelihood of reporting regardless of whether other non-drug-related factors could also have accounted for the adverse event.

Table 8. 1997 "Possible" ADE Animal Injury Reports Listed by Top-10 Ranked Adverse Clinical Manifestations (n=3,817)