Signal Detection for Cyclophosphamide: Canadian Adverse Reaction Monitoring Program (CADRMP)

Abstract

Objective: The objective of the study was to identify possible toxic signal induced by cyclophosphamide treatment by searching database from Canadian Adverse Reaction Monitoring Program (CADRMP). Methods: A total of 10429 reports of patients between January 1970 to March 2010 were downloaded from CADRMP website. These reports contained information of adverse events associated with all other drugs inclusive of cyclophosphamide . Adverse drug reaction (ADR) signal detection were determined by proportional reporting ratio (PRR), reporting odds ratio (ROR), PRR calculated by chisquare statistics, 95% confidence interval of PRR, observed to expected (O/E) ratio and De Mouchel method calculated PRR. Information component (IC) was given by Bayesian confidence propagation neural network. (As per regulatory criteria, PRR ≥ 2, ROR ≥ 1, chi-square statistics calculated PRR ≥ 4 and lower bound of 95% CI of PRR ≥ 1 to consider particular adverse drug reaction as a signal. Further by BCPNN method, if IC−2SD≤0 then that drug-ADR pair considered as no signal; if 0<IC−2SD ≤ 1.5, then that drug-ADR pair considered as weak signal; if 1.5<IC−2SD ≤ 3.0, then that drug-ADR pair considered as middle signal; if IC−2SD > 3.0, then that drug-ADR pair considered as strong signal). Results: A total of 108 reports of cyclophosphamide-induced neutropenia were reported in CADRMP database. The PRR was found to be 4.7396 and by the Du Mouchel method it was 3.9310. Further, the PRR calculated by chi-square statistics was 236.02518. The lower and upper limits of 95% CI of PRR was found to be 1.3484 and 1.7634, respectively. The O/E ratio was found to be 3.9322 and ROR was found to be 4.9704. The value of PRR ≥ 2, ROR ≥ 1, chi-square statistics calculated PRR ≥ 4 and lower limit of 95% CI of PRR ≥ 1 indicates signal for neutropenia caused by cyclophosphamide. The value of IC-2SD was 1.6852 indicates middle signal for cyclophosphamide-induced neutropenia. The signal of neutropenia coupled with cyclophosphamide was found potent enough to cause neutropenia in Canadian population.

Ocular adverse events associated with anti-VEGF therapy: A pharmacovigilance study of the FDA adverse event reporting system (FAERS)

“…According to BCPNN signal strength standard, medium and strong signals with signal value IC-2SD ≥ 1.5 were selected for analysis and discussion (Sharwan and Bhaswat, 2015). All analyses were performed using Microsoft EXCEL 2019.…”