PVmap™ of the Week
ProSanos has initiated a program to publicly provide a limited set of PVmaps™
generated from the FDA's Adverse Event database. A different map will be posted
each week focusing on a drug and adverse event combination that is a current topic
of discussion within the industry. For more information about PVmaps
or the PVmap of the Week program, .
Pergolide & Risk of Cardiac Valve Regurgitation (1/7/2007)
The January 4, 2007 New England Journal of Medicine contains an article3
which discusses a previously suspected risk of cardiac valve regurgitation with
pergolide, marketed as Permax®, and related dopamine agonists. Dopamine agonists
are typically used for treating Parkinson's disease, and may be used for Restless
Leg Syndrome.
This PVmap visually investigates whether statistically significant number
of cardiac valve regurgitation cases in pergolide patients had been reported to the
FDA via its Adverse Event Reporting System (AERS), using data covering the period from
2001 through the first quarter of 2006. This is a Drug-focused PVmap, which shows
strongest (most statistically significant) signals in the upper right hand corner
of the graph. The striking display above shows a strong statistical association
between the use of pergolide and valvular disease. The visual presentation makes
it particularly easy for the investigator to interpret signals that are "spread
out" over a number of MedDRA terms, as this one is. A Trajectory PVmap, for
aortic valve regurgitation (not shown) indicates that this signal crossed into the
red zone of statistical significance for Pergolide in the third quarter of 2003.
(Trajectory PVmaps trace the emergence of signals over time.)
Drug-focused PVmaps
This is a Drug-focused PVmap, allowing you to visualize which adverse events are
most highly associated with a particular drug of interest. In this case, the
drug is pergolide and the red dots represent Adverse Events reported in
the AERS database to be associated with pergolide. On the horizontal axis of this
graph is the reporting ratio, which compares the number of cases of a
particular adverse event with the number expected due to chance alone. The
vertical axis expresses the statistical significance of the finding. Dots
above the horizontal blue line and to the right of the vertical blue line
represent "significant signals". The adverse events with the strongest
association to pergolide appear at the top and to the right on the PVmap.
Disclaimers
- Potential risks highlighted by drug safety analysis must be balanced against
the clinical benefit attained by the use of a pharmaceutical product in a given
clinical situation. Nothing in these analyses is intended to influence the
practice of medicine, nor to weigh the benefits of one product over another.
- Whether the reporting ratio of an adverse event is high enough to influence the
decision to use a given product or products can only be determined by a complete
analysis of the benefits, risks, and therapeutic alternatives.
- Use of the publicly available FDA AERS data does not imply endorsement or
agreement of the findings by the FDA Center for Drug Evaluation and Research.
- There are many factors that can influence how the adverse events are reported
in the AERS database and may impact the resulting safety signal. These include but
are not limited to: publicity and media attention, litigation, length of time drug
is on the market, whether the event in question has been previously attributed
to the drug, the source of the report, etc.
- AERS data must often be "cleaned" prior to analysis. This process may include
de-duplication, reconciliation of misspelled product names, mapping of adverse
events terms, and other manipulations which could introduce bias into the analysis.
- PVmaps has been evaluated as a safety signal investigation tool for over two years.
References
- Schade R, Andersohn F, Suissa S, et al. Dopamine Agonists
and the Risk of Cardiac-Valve Regurgitation. N Engl J Med 2007;356:29-38.
