Acting Chairperson's Summary - 2005 VMAC
Veterinary Medicine Advisory Committee Meeting
Food and Drug Administration
January 31, 2005, Doubletree Hotel, Rockville, MD
Issue: Voluntary Recall of ProHeart 6® (NADA 141-189)
Committee Members in attendance:
Susanne Aref, Ph.D., John J. McGlone Ph.D., Corrie Brown, DVM, Ph.D., Lisa Nolan, DVM, Ph.D., Gregory Jaffe, Mark G. Papich, DVM, Richard A. Sams, Ph.D., Katrina L. Mealey, DVM, Ph.D., Arthur L. Craigmill, Ph.D. (Acting Chairperson)
Invited, Voting Consultants in attendance:
Charles L. Bennett, MD, Ph.D., M.P.P., Tom Nelson, DVM, Michael I. Luster, Ph.D., Michael R. Peterson, DVM, MPH, Dr.PH, M. Gatz Riddell, Jr., DVM, MS, Sam Groseclose, DVM, MPH, Lauren A. Trepanier, DVM, Ph.D.
Executive Secretary: Aleta Sindelar, R.N.
The meeting began at 8:00 AM EST with a presentation by Dr. Stephen Sundlof, Director of the Center for Veterinary Medicine (CVM). Dr. Sundlof introduced the committee and the invited consultants, and presented the issue before the committee for consideration.
The meeting continued with a presentation by Jennifer Gresock, Food and Drug Administration (FDA), covering the legal framework for reporting adverse drug events (ADEs). Dr. Margarita Brown, FDA/CVM, presented information about how ADEs are reported to and scored by the FDA. Drs. Lynn Post, FDA/CVM, and Margarita Brown presented information about the (ADE) reports which had been received by CVM about ProHeart 6®, the only injectable heartworm prevention product approved for dogs. The reports prompted discussions with Fort Dodge Animal Health (FDAH) and resulted in the voluntary recall of ProHeart 6® last year. Dr. Brown ended the CVM presentation by outlining CVM’s view of the information provided by FDAH about ProHeart 6® adverse reactions.
The CVM presentation was followed by presentations by FDAH personnel and consultants. Dr. Rami Cobb, FDAH, introduced Dr. Larry Glickman, an epidemiologist from Purdue University who presented the results of a study done using data from Banfield, The Pet Hospital® databases, with reference to ProHeart 6® and compared it to two approved oral heartworm preventives. The summaries and interpretations by Dr. Glickman were based on data (The Banfield Data) that had not been submitted to the agency for review and response prior to the VMAC meeting. Dr. David Hustead, FDAH, also made a presentation of the FDAH position and interpretation of ADE reports submitted to FDAH.
After these presentations the VMAC committee and consultants began rounds of questions directed to both CVM and FDAH personnel and consultants. Most of the questions related to methodologies used in assessing the cases, how data were collected, pharmacokinetics of the microsphere formulation, and other factors which might affect the potential toxicity or allergenicity of the ProHeart 6® formulation.
After a break for lunch, the rounds of questions continued, and then at 1:00 PM the floor was opened for public comments. Dr. Craigmill, Acting VMAC Chairperson, read a statement about the public comments into the records, and each of the 15 registered speakers was allocated 5 minutes time to make his/her presentation. Several speakers also chose to show pictures using the computer screen projector.
After completion of the public comments, the VMAC committee and consultants had additional questions for the CVM and FDAH personnel and consultants. At the conclusion of the questions, Dr. Craigmill read each CVM VMAC question posed to the committee and asked each voting member and consultant to register their opinion.
The first question posed to the committee was: Based on the presentations and information provided is ProHeart 6® safe for use in dogs? Yes or No
(It should be noted that almost all of the responses to the first question were qualified with a concern that more information and data were needed to establish the safety or the risks associated with the use of ProHeart 6®.)
Dr. Aref: NO, however we need more data, it is very hard to answer.
Dr. Brown: YES, the Banfield data are pretty convincing.
Mr. Jaffe: NO, but we need real incidence rate information, continue the withdrawal for the time being.
Dr. Mealey: NO, there are safer alternatives; it is hard to determine if it is the drug or the carrier which is causing the anaphylactoid reactions.
Dr. McGlone: NO, but not enough data to do a proper risk-benefit analysis as the risks are very low.
Dr. Nolan: YES, Banfield data are compelling.
Dr. Papich: NO, but much more data needed to decide if it is really safe or not. Need to be more careful with prophylactic medications than therapeutic ones.
Dr. Bennett: YES, and though the reports are worrisome, we need more studies like the Banfield study to truly decide.
Dr. Luster: NO, since there are safer alternatives now, need risk-benefit analysis.
Dr. Groseclose: NO, we need more data however since quality data are lacking.
Dr. Nelson: YES, there are too many other possible causes of the reactions reported.
Dr. Peterson: YES, the Banfield data are not perfect but very good, and the real question should be how this product compares to other heartworm preventives.
Dr. Riddell: YES, we need to consider the risk-benefit perspective and owner compliance issue.
Dr. Trepanier: NO, even though the reactions are rare, really need a 30 day follow-up study to clarify this issue.
Dr. Craigmill: YES, there are certainly a lot of ADE reports, but the incidence rate is very important as are issues of acceptable risk in comparison to other products and disease.
Second Question: If there are remaining safety concerns with ProHeart 6®, what additional avenues of research could be explored to mitigate and/or prevent the adverse events?
Suggestions from the panel and consultants include additional studies, both new prospective cohort and retrospective case-control studies; performance of a risk benefit analysis taking into account owner non-compliance when using oral heartworm preventives; additional clinical trials; additional pharmacokinetic trials to explore the effects of increased body temperature on release of the drug from the injection site; release of the Banfield data to the FDA for analysis; possible “black-box” labeling of the drug to emphasize the possible risks; development of more information about the drug’s effects on different life stages of the parasite; meta-analysis of data collected from multiple studies or areas to increase the power of detecting and quantifying the adverse events in comparison to other heartworm preventives.
The meeting was adjourned at 5:15 PM EST
Respectfully submitted: Arthur L. Craigmill, Ph.D. Acting Chairperson, VMAC