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Novel adverse events of bevacizumab in the US FDA adverse event reporting system database: a disproportionality
Behrooz K Shamloo1, Pankdeep Chhabra, Andrew N Freedman
1University of Nevada School of Medicine-Nevada Cancer Institute, Las Vegas, NV, USA.
Background:
Bevacizumab is the first in its class, vascular endothelial growth factor (VEGF) inhibitor that was initially approved by the US FDA in 2004 for the treatment of metastatic colon cancer and other solid tumors. Preapproval clinical trials, particularly for oncology drugs, are limited in their ability to detect certain adverse effects and, therefore, the FDA and pharmaceutical sponsors collect and monitor reports of adverse events (AEs) following approval.
Objective:
The purpose of this study was to screen the FDA's Adverse Event Reporting System (AERS) database for novel AEs that may be attributed to bevacizumab.
Methods:
The FDA AERS database was used to identify all AE reports for bevacizumab from February 2004 to September 2009. Disproportionality analysis was conducted for bevacizumab against all other drugs in the background by setting statistical significance at proportional reporting ratio (PRR) ≥2, observed case count ≥3 and chi-square ≥4. Subsequent clinical evaluation was performed to determine the clinical relevance of the findings and to group related events.
Results:
A total of 523 Preferred Terms (PTs) were disproportionally reported; following clinical review 63 (12%) were found to be both unlabelled and of clinical importance. These PTs were grouped into 15 clinical disorder groups. Among the clinical disorders, electrolyte abnormalities had the greatest number of reports (n = 426) followed by cardiovascular events (n = 421), gastrointestinal events (n = 345), nervous system disorders (n = 106) and pneumonitis (n = 96). On sensitivity analysis, a number of clinically important unlabelled disorders, such as necrotizing fasciitis, vessel wall disorders, arrhythmia and conduction disorder and autoimmune thrombocytopenia still met the statistical significance criteria.
Conclusions:
During the study period, out of 12 010 AE reports mentioning bevacizumab, it was listed as the suspect drug in 94.2% of the reports. Our disproportionality analysis identified many events that are already recognized as AEs of bevacizumab, but it also identified a number of clinically important unlabelled terms, which if confirmed in future studies would have potential implications for use of bevacizumab in clinical practice.
Insights
This study analyzed FDA data to find new side effects of bevacizumab (VEGF inhibitor). It identified several clinically important, unlabelled adverse events, suggesting potential impacts on patient care.
Area of Science:
- Pharmacovigilance and drug safety analysis.
- Oncology drug adverse event monitoring.
Background:
- Bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, was approved in 2004.
- Post-approval monitoring is crucial for detecting rare adverse events (AEs) missed in pre-approval trials.
Purpose of the Study:
- To screen the FDA Adverse Event Reporting System (AERS) database for novel AEs associated with bevacizumab.
- Identify and evaluate potentially new safety signals for bevacizumab.
Main Methods:
- Utilized FDA AERS database from February 2004 to September 2009.
- Performed disproportionality analysis using proportional reporting ratio (PRR), observed case count, and chi-square.
- Conducted clinical evaluation to determine relevance and group related events.
Main Results:
- Identified 523 disproportionally reported Preferred Terms (PTs); 63 were unlabelled and clinically important.
- Top reported clinical disorders included electrolyte abnormalities, cardiovascular events, and gastrointestinal events.
- Clinically significant unlabelled disorders like necrotizing fasciitis and autoimmune thrombocytopenia were noted.
Conclusions:
- Bevacizumab was the suspect drug in 94.2% of 12,010 AE reports analyzed.
- The analysis confirmed known AEs and identified clinically important unlabelled adverse events.
- These findings may have implications for the clinical use of bevacizumab pending further studies.
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