Variable importance for projection (VIP) scores for analyzing the contribution of risk factors in severe adverse events to Xiyanping injection

BACKGROUND: Age and herb-drug combination are risk factors for the severity of Xiyanping injection (XYP) associated adverse events (AEs). OBJECTIVE: To analyze risk factors contributing to the severity of XYP’s AEs using a variable importance for projection (VIP) method. METHODS: AEs related to the use of XYP were extracted from the China National Adverse Drug Reaction Monitoring Information System (2004–2017) and classified as general or severe. Data were analyzed with respect to age and 12 herb-drug combinations, including ribavirin (RB), ceftriaxone, penicillin sodium, ambroxol hydrochloride (AH), clindamycin, cefoxitin sodium, azithromycin (AZM), ceftazidime, amoxicillin sodium/potassium clavulanate, levofloxacin hydrochloride, sodium cefazolin pentahydrate, and acyclovir according to VIP scores and correlation coefficient (Coeff). RESULTS: A total of 21,714 AEs (general 20,660; severe 1054) related to XYP combinations were included. Using XYP alone tended to produce general AEs (All VIP = 3.124; 1.329; 1.857; 2.169; 2.400, Coeff < 0). For all set, 0–6 years old patients tend to have general AEs (VIP = 2.425, Coeff < 0), while those > 41 years old patients tend to have severe AEs (VIP = 1.180; 2.323, Coeff > 0). For 0–40 years old patients, XYP-RB combination had a greater impact on the severity of AEs (VIP = 1.158; 1.360; 1.147, Coeff > 0). For 7–17 years old patients, XYP-AZM combination tended to produce general AEs (VIP = 1.502, Coeff < 0). In individuals > 65 years old, XYP-AH combination tended to result in severe AEs (VIP = 1.232, Coeff > 0). CONCLUSIONS: VIP method was expected to effectively analyze risk factors in affecting the severity of AEs and control AEs more effectively. Age is the key factor contributing to the severity of AEs, and there are different influence directions. It is recommended that clinicians pay closer attention to the metabolic characteristics of different age groups. It is safe to use XYP alone and strictly implementing standardized operations such as medication interval and flushing will avoid undesired AEs.