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Aromatase inhibitors associated osteonecrosis of jaw: signal refining to identify pseudo safety signals

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Abstract

Background Signal generation through data mining algorithms is an innovative and emerging field in pharmacovigilance. Early detection of safety signals is important for public health safety. However, the possibility of generating pseudo signals should not be overlooked. Objective Our study aimed to identify potential signals of aromatase inhibitors associated Osteonecrosis of Jaw and assess the possibilities of the safety signal to be a pseudo signal/false positive in FDA Adverse Event Reporting System (FAERS). Setting Spontaneously reported data in FAERS database. Methods Data for this study were obtained from the public release of data in FAERS. OpenVigil, a pharmacovigilance analytical tool was used to access FAERS data. Reporting Odds Ratio (ROR) was used to assess the relation between the drug and adverse event. A value of ROR-1.96SE  > 1, (SE—standard error) was considered positive. Main outcome measure Signal strength. Results FAERS database had a total of 15,178 reports for Osteonecrosis of Jaw. Amongst which 617 reports were associated with aromatase inhibitors. Signal strength ROR (lower bound of the 95% CI) for letrozole, anastrozole and exemestane associated Osteonecrosis of Jaw without any background correction was 8.34, 6.64 and 15.14 respectively. Upon removing the reports of concomitantly administered drugs (bisphosphonates and denosumab), signal strength drastically decreased to 0.03, 0.36 and 0.47 for letrozole, anastrozole and exemestane respectively. The signal strength of bisphosphonates and denosumab associated Osteonecrosis of Jaw was not changed significantly upon removal of aromatase inhibitors. Conclusion Our study concluded that the signal generated for aromatase inhibitors associated Osteonecrosis of Jaw in FAERS database can be false positive. Careful background corrections with identification of those risk factors are imperative to exclude false positive results.

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Acknowledgements

We thank Ms. Radhika, Department of community medicine, Ramaiah Medical College, Bengaluru, India, who clarified all the statistical related doubts. We thank our Dean & Professors, Faculty of Pharmacy, M S Ramaiah University of Applied Sciences who provided insight and expertise that greatly assisted the research. We thank Dr.Ruwen Böhm, Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig–Holstein, Campus Kiel, Kiel, Germany, for assistance with open VigilFDA v1.0.2 that greatly improved the manuscript.

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  1. Department of Pharmacy Practice, Faculty of Pharmacy, M S Ramaiah University of Applied Sciences, New BEL Road, Bengaluru, 560054, Karnataka, India

    Reddy Neha, Elsa Beulah, Bellapu Anusha, Sharma Vasista, Chacko Stephy & Viswam Subeesh

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  1. Reddy Neha
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  2. Elsa Beulah
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Correspondence to Viswam Subeesh.

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Neha, R., Beulah, E., Anusha, B. et al. Aromatase inhibitors associated osteonecrosis of jaw: signal refining to identify pseudo safety signals. Int J Clin Pharm 42, 721–727 (2020). https://doi.org/10.1007/s11096-020-01018-z

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