Preliminary Results of a Novel Algorithmic Method Aiming to Support Initial Causality Assessment of Routine Pharmacovigilance Case Reports for Medication-Induced Liver Injury: The PV-RUCAM.

INTRODUCTION

Data incompleteness in pharmacovigilance (PV) health records limits the use of current causality assessment methods for drug-induced liver injury (DILI). In addition to the inherent complexity of this adverse event, identifying cases of high causal probability is difficult.

OBJECTIVE

The aim was to evaluate the performance of an improved, algorithmic and standardised method called the Pharmacovigilance-Roussel Uclaf Causality Assessment Method (PV-RUCAM), to support assessment of suspected DILI. Performance was compared in different settings with regard to applicability and differentiation capacity.

METHODS

A PV-RUCAM score was developed based on the seven sections contained in the original RUCAM. The score provides cut-off values for or against DILI causality, and was applied on two datasets of bona fide individual case safety reports (ICSRs) extracted randomly from clinical trial reports and a third dataset of electronic health records from a global PV database. The performance of PV-RUCAM adjudication was compared against two standards: a validated causality assessment method (original RUCAM) and global introspection.

RESULTS

The findings showed moderate agreement against standards. The overall error margin of no false negatives was satisfactory, with 100% sensitivity, 91% specificity, a 25% positive predictive value and a 100% negative predictive value. The Spearman's rank correlation coefficient illustrated a statistically significant monotonic association between expert adjudication and PV-RUCAM outputs (R = 0.93). Finally, there was high inter-rater agreement (K  = 0.79) between two PV-RUCAM assessors.

CONCLUSION

Within the PV setting of a pharmaceutical company, the PV-RUCAM has the potential to facilitate and improve the assessment done by non-expert PV professionals compared with other methods when incomplete reports must be evaluated for suspected DILI. Prospective validation of the algorithmic tool is necessary prior to implementation for routine use.