| Information
About the Voluntary Recall of ProHeart 6
Response to FDA Concerns
In response to the concerns raised by the FDA, Fort
Dodge Animal Health has compiled the following data,
which we believe solidly support our claims of safety
and efficacy. We are confident this information will
help clarify this situation, and will help enable you
to successfully address questions and concerns that
may arise from pet owners.
FDA Concern
FDA has cited concern with the number of adverse reactions
and deaths reported for ProHeart 6.
Fort Dodge Response
Potential adverse events reported to the FDA are unfiltered,
meaning all reported potential events are submitted
without regard to cause and effect. Cases subsequently
determined not to be related to the product remain in
the overall reporting numbers, and are used to draw
medical conclusions that dramatically overstate the
incidence of various conditions.
Since launch in 2001 through August 2004, the overall
rate of reports for ProHeart 6 has been calculated at
approximately 3 unfiltered reports for each 10,000 doses
sold. Independent data from one of the most comprehensive
databases available in the U.S. indicates a reporting
rate of 4 reports per 10,000 doses actually administered
to dogs. Considering the difference between "doses
sold" to veterinarians and "doses administered,"
we believe this data to be representative of what is
occurring in actual field use, and disagree with the
FDA's assertion that there is significant "under
reporting" with the product. Our belief is underscored
by the fact that ProHeart 6 is administered only by
veterinarians, and has received undue media and Internet
attention, both of which increase the likelihood of
event reporting.
Nonetheless, the breakdown of unfiltered reports is
as follows (based on reports per 10,000 doses):
· For allergic reactions, the number of unfiltered
reports for May 02 - April 03 was 2.2 per 10,000 doses.
From May 03 - April 04, that number was 0.85 per 10,000
doses.
· For illness, the number of unfiltered reports
for May 02 - April 03 was 2.1 per 10,000 doses. >From
May 03 - April 04, that number was 0.98 per 10,000 doses.
· For death, the number of unfiltered reports
for May 02 - April 03 was 0.4 per 10,000 doses. >From
May 03 - April 04, that number was 0.28 per 10,000 doses.
Regarding death reports for ProHeart 6, the FDA was
quoted in the November 2003 issue of DVM News Magazine:
"The FDA claims that nine of the 240 reported deaths
are directly tied to the drug." This statement
indicates the FDA's conclusion that the vast majority
of the deaths reported for ProHeart 6 are unrelated,
which is in line with Fort Dodge's data.
Noted in this document are examples of dogs included
in the adverse event database. Despite medical evidence
that reflects health issues not related to ProHeart
6, the cases are included in the analysis of the database
and the subsequent conclusions.
FDA Concern
In the FDA news release, the Agency cited a concern
with liver and abnormal bleeding issues.
Fort Dodge Response
Fort Dodge disagrees with the FDA's conclusions about
the magnitude of these issues, as no consideration was
given to the basic principle of epidemiology, which
requires events be evaluated in the context of the population
at risk.
Research by Bronson (Am J Vet Res, Vol. 43, No. 11,
p.2057-2059, 1982) shows the mean age at death from
hepatic necrosis as 4.9 years. The FDA's own data reflects
the average age for liver signs, with relation to ProHeart
6 reports, as 4.5 years, which is in keeping with the
baseline canine population in the U.S.
Based on unfiltered reports with some reference to hematologic
signs/autoimmune signs, the incidence rate for ProHeart
6 is 0.0025 percent or one in approximately 31,000 doses.
Again, Bronson reported that one percent of all deaths
in dogs were due to hemolytic anemia. Even with unfiltered
reporting numbers, ProHeart 6 is well below the baseline
of disease for the U.S. canine population.
FDA Concern
In a presentation to Fort Dodge, FDA cited unusual cardiac
complications as a concern with ProHeart 6.
Fort Dodge Response
Based on the unfiltered data, the frequency of total
"cardiac" reports is 0.2 reports per 10,000
doses. In the U.S. canine population, there is an underlying
incidence of heart disease in dogs, and a higher prevalence
is recognized in boxers than in the general canine population.
The FDA has stated finding "atypical heart problems"
in boxers because of cases with no macroscopic dilation.
Boxers, in fact, have a genetic predisposition to cardiomyopathy.
Two distinct types are recognized. One has macroscopic
dilated findings, while the other does not (Gough and
Thomas, Breed Disposition to Disease in Dogs and Cats,
ISBN 1-4051-0748-0).
FDA Concern
The FDA has cited cancer as a concern for ProHeart 6
and has stated a "suspicious timing of cancer,
four to 30 days" and in young dogs.
Fort Dodge Response
In our opinion and those of experts we have consulted,
the timing suggested by the FDA (4 to 30 days post administration)
is not biologically feasible. And the data reflects
the age of dogs included in the reporting numbers is
less than the rate of cancer seen in the general canine
population (Cancer Incidence in Dogs Survey, 1952-1963,
and Cohen et al., Cancer Research, 34:2859-2868, 1974).
It is estimated that almost half of all pets over the
age of 10 will develop cancer (Cancer in Dogs and Cats,
Brakke Consulting, 2002). While cancer is more common
in older dogs, it does occur in young ones, as well.
In the unfiltered reports for ProHeart 6, the rate of
cancer is 0.07 reports per 10,000 doses. Nearly 77%
of these cases are in dogs older than six years. The
Veterinary Cancer Registry shows 75% of dogs with cancer
are seven years or older.
Cohen, et al. (Cohen, et al., Cancer Research, Epidemiological
Analysis of the Most Prevalent Sites and Types of Canine
Neoplasia Observed in a Veterinary Hospital, 34: 2859-2868)
reported 2,499 cancer cases in 60,000 dogs presented
to veterinary hospitals over a 12-year period. The rate
of prevalence was 4.2%. The unfiltered ProHeart 6 database
shows 122 reports out of 18.2 million doses (through
April 2004) with a diagnosis of cancer, which is considerably
lower than that seen in the general canine population.
In addition, the wide range of cancer seen in the unfiltered
ProHeart 6 reports is reflective of the range of normally
occurring cancers seen in the general canine population.
An example of a dog included in the cancer category
for ProHeart 6 is as follows:
The dog, a 10.5-year-old Yorkie with a known sensitivity
to ivermectin (lethargy and vomiting), was treated with
ProHeart 6. Approximately four months later, the dog
presented with anorexia, ataxia and lethargy. Initial
diagnostic evaluation revealed bilateral luxating patellas.
The dog was also thought to have a possible liver problem
or a tumor, but the owner initially declined medical
treatment and a further diagnostic evaluation. A referral
veterinary ophthalmologist later examined this dog for
a vision problem. While the veterinarian could not make
an initial definitive diagnosis, he did note that if
this problem were pharmaceutically related, he would
expect the problem to be symmetric, not asymmetric as
exhibited by this dog.
Eight months after the injection, the dog was diagnosed
with lymphoma in its right eye. The veterinary ophthalmologist
noted he has seen this same problem in a number of dogs
that had not been administered ProHeart 6. Evidence
of glaucoma was found in the other eye. Approximately
one month later, the dog was euthanized at the owner's
request because of the dog's difficulties. Two veterinarians
told the owner that the lymphoma most likely spread
to other parts of this dog's body. The referral veterinarian
suggested a necropsy be performed; the owner declined.
Despite the evaluations of the attending veterinarians,
FDA has assigned the following signs in this dog as
being "probably related to the drug." - Anorexia,
Depression/Lethargy, Neoplasm, Weight Loss, WBC High/Blood
Problem, Ataxia, Circling, Blindness, Hyphaema and Eye/Eyelid
Lesion.
Lymphoma is a common cancer in dogs, with a reported
incidence of 11.4 cases per 10,000 dogs per year (Morris
& Dobson, ISBN, 0-632-05282-1).
FDA Concern
In a presentation to Fort Dodge, the FDA cited a concern
with the efficacy rate for ProHeart 6.
Fort Dodge Response
Based on unfiltered reports, the efficacy rate for ProHeart
6 continues to be solid - 99.997%.
FDA Concern
The FDA has cited a concern with unfiltered reports
of anaphylaxis for ProHeart 6.
Fort Dodge Response
Unfortunately, almost any drug can trigger an allergic
reaction. After ProHeart 6 was launched and anaphylaxis
was observed, labeling changes were instituted promptly
to describe the post-launch experience.
The rate of anaphylactic reactions has decreased from
2.2 per 10,000 doses in May 02-April 03 to 0.85 per
10,000 doses in May 03-April 04. In addition, there
has also been a decrease in the "illness"
category of reports from 2.1 per 10,000 doses to 0.98
per 10,000 doses, which supports the premise that many
of the illnesses reported (vomiting, diarrhea) were
allergy related
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| Frequently
Asked Questions
To answer some of your questions and those raised by
your clients, Fort Dodge has drafted the following information
for your reference. If you have questions not covered
in this document or you would like to discuss any issues
further, please contact our Professional Services department
at 1-800-533-8536.
1. What is the current situation with ProHeart
6?
Fort Dodge Animal Health has announced it will voluntarily
comply with the U.S. Food and Drug Administration Center
for Veterinary Medicine's request to temporarily cease
marketing and recall ProHeartâ 6 from the veterinary
level until the FDA's questions regarding safety are
resolved. Fort Dodge Animal Health also announced its
strong support for FDA's formation of an independent
Advisory Panel to review and evaluate safety data on
ProHeart 6.
While Fort Dodge Animal Health is cooperating with FDA's
request for a recall, we strongly disagree with the
Agency's interpretation of the data and the conclusions
that were drawn. The Company fully supports the initiation
of the review process, and will work closely with FDA
to provide the necessary information for the panel to
make a fair and accurate assessment of these data. We
look forward to working with the panel and remain confident
in the safety and efficacy of ProHeart 6.
2. Was Fort Dodge required to comply with the FDA's
request to voluntarily recall ProHeart 6?
While the announcement indicates this is a voluntary
recall, it is important to understand the FDA was going
to issue a press release that was very severe in its
wording. It was our judgment that this would have put
veterinarians in a very undesirable position with their
clients. While not a perfect solution, we have chosen
to pursue the expert Advisory Panel as the best means
of reversing this FDA's decision.
3. Why did Fort Dodge not contact veterinarians
in advance about the voluntary recall?
Fort Dodge specifically requested the FDA hold its news
release until the company could contact its customers
and communicate to them the voluntary recall of ProHeart
6. Fort Dodge felt strongly that to allow the media
to drive the communication of this information would
be extremely detrimental to veterinarians, as well as
pet owners. The FDA refused our request.
Unfortunately, we could not respond to the FDA's position
until they issued their press release, which occurred
after 4:30 p.m. Eastern Time on Friday, 03 September
2004. We sincerely regret that the timing of this process
was such that we were unable to alert our customers
in a more timely manner. While dissemination of information
to the media can be instantaneous and far-reaching,
providing immediate information to tens of thousands
veterinarians across the country proves significantly
more difficult.
We have posted these materials on the Veterinary Information
Network, as well as www.proheart6dvm.com, for your convenience.
If you have further questions, please call our Professional
Services department at 1-800-533-8536.
Fort Dodge Animal Health has consistently communicated
with veterinarians about issues relevant to the animal
healthcare industry, including ProHeart 6. Effective
communication with our constituencies has been and continues
to be a priority for Fort Dodge.
4. If ProHeart 6 has already been voluntarily
recalled, why is an independent advisory committee being
convened?
While Fort Dodge has agreed to voluntarily recall ProHeart
6 from the market, we continue to be confident in the
safety and efficacy of the product. We disagree with
the FDA's interpretation of the data and the conclusions
that have been drawn, and feel strongly the data need
to be thoroughly reviewed and evaluated by an independent
committee of experts from the animal health/veterinary
industry. Fort Dodge is pushing for an immediate selection
of the committee and review of the data.
5. Does Fort Dodge plan to reintroduce the product
at a later time?
Fort Dodge Animal Health will make all reasonable efforts
to resolve the current concerns and reintroduce ProHeart
6. The Company is committed to working with the FDA
to address its concerns and to take the necessary actions
to make ProHeart 6 available to veterinarians and dog
owners throughout the U.S.
6. What should dog owners do if they have used
ProHeart 6 for their dog(s)?
Fort Dodge remains confident in the safety and efficacy
of ProHeart 6. Pet owners with concerns should contact
their veterinarian or they may call Fort Dodge's Professional
Services department at 1-800-533-8536. Veterinarians
with questions regarding specific patients should call
Fort Dodge Professional Services for further discussion.
7. What should I do if a pet owner feels his/her
dog has had a reaction to ProHeart 6?
Veterinarians or pet owners with concerns may call our
Professional Services department at
1-800-533-8536.
8. If ProHeart 6 is not available, what should
dog owners' use?
While ProHeart 6 is unavailable, we urge dog owners
to consult with their veterinarians to discuss alternative
preventatives.
9. How has the Internet impacted ProHeart 6?
During the past year, misinformation about ProHeart
6 has spread rapidly via the Internet. While the Internet
can be a valuable source of information, it is also
full of opinion and conjecture presented as fact. Unfortunately,
it is often difficult to tell the difference between
the two. Fort Dodge strongly encourages interested individuals
to fully investigate websites and verify the accuracy
of information presented on those sites. Fort Dodge
consistently reminds pet owners that the best resource
for information is the veterinarian. Not only can a
veterinarian review the data concerning ProHeart 6,
but he/she can also evaluate the health needs of the
animal and determine the most appropriate heartworm
prevention program.
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