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. On a regular basis, we will post a map focusing on a drug and adverse event combination that is a current topic of discussion within the industry or in the published literature. For more information about PVmaps or the PVmap of the Week program, .

Oseltamivir and Hallucinations (11/03/2008)
A recent "Dear Healthcare Professional" letter⁶³ discusses the potential for neuropsychiatric adverse events with the influenza drug oseltamivir (marketed as TAMIFLU®). We used CLAERITY software to obtain a visual PVmap representing reports for oseltamivir in the FDA Adverse Event Reporting System (AERS) database from 1997 through the first quarter of 2008:

In this view, the most prominent signal of disproportionate reporting for oseltamivir is for abnormal behaviour. Interestingly, when we click on the map point to get a demographic summary for this drug-event combination, we note a young, male predominance:

Abnormal behaviour is a broad and ambiguous MedDRA® Preferred Term (PT), and we would like to get a more specific picture of what is going on with these patients. For terms like this, we find that the best tool for further investigation is a "Potential Syndrome PVMap", which identifies PTs that are statistically associated with the PT abnormal behaviour in patients taking oseltamivir. While we are not technically looking for a syndrome here-that is, a cluster of related symptoms-the Potential Syndrome PVmap can help produce a clear idea of why a hard-to-decipher PT is appearing:

The result shows the predominance of hallucination and delirium discussed in the Dear Healthcare Provider letter. We often find that Potential Syndromes PVmaps are useful in clarifying the meaning of signals of disproportionate reporting for MedDRA terms that are too general to be interpretable on their own.

About Drug-focused PVmaps
Above is a Drug-focused PVmap, allowing you to visualize which adverse events are most highly associated with a particular drug of interest. In the map directly above, the drug is oseltamivir and the red dots represent Adverse Events reported in the AERS database to be associated with oseltamivir. On the horizontal axis of this graph is the reporting ratio that 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 oseltamivir appear at the top and to the right on the PVmap.

About Potential Syndrome PVmaps

The second map above is a Potential Syndrome PVmap, which allows you to visualize what co-occurring events are significantly associated with a specified drug/adverse event combination. In this case, the drug/adverse event combination is the drug oseltamivir reported in association with abnormal behaviour. The red dots on the first map represent additional events (MedDRA preferred terms) reported for patients who took oseltamivir and reported abnormal behaviour. On the horizontal axis of this graph is the reporting ratio, which compares the actual rate of occurrence of each event in patients with oseltamivir/abnormal behaviour compared to the event rate 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 co-occurring events that are most highly associated with the drug/event combination of interest appear at the top and to the right of the PVmap.

Sponsor companies have used ProSanos PVmaps for multiple therapeutic areas. To learn more about PVmaps projects in your therapeutic area or indication, please .

Disclaimers

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. PVmaps has been evaluated as a safety signal investigation tool for over two years.

References

63. Bigerson L. IMPORTANT PRESCRIBING INFORMATION. February 2008. Accessed on the World Wide Web at This URL , 12 March 2008.