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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.
Drug Saf. 2017 08; 40(8):715-727.DS

Abstract

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 w = 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.

Authors+Show Affiliations

Patient Safety, Novartis Pharma AG, Basel, Switzerland. erik.scalfaro@gmail.com.Patient Safety, Novartis Pharma AG, Basel, Switzerland.Preclinical Safety, Novartis Institutes for BioMedical Research, Basel, Switzerland.Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.Patient Safety, Novartis Pharma AG, Basel, Switzerland. School of Life and Medical Sciences, University of Hertfordshire, Hatfield, England, UK.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28508325

Citation

Scalfaro, Erik, et al. "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." Drug Safety, vol. 40, no. 8, 2017, pp. 715-727.
Scalfaro E, Streefkerk HJ, Merz M, et al. 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. Drug Saf. 2017;40(8):715-727.
Scalfaro, E., Streefkerk, H. J., Merz, M., Meier, C., & Lewis, D. (2017). 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. Drug Safety, 40(8), 715-727. https://doi.org/10.1007/s40264-017-0541-2
Scalfaro E, et al. 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. Drug Saf. 2017;40(8):715-727. PubMed PMID: 28508325.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Scalfaro,Erik, AU - Streefkerk,Henk Johan, AU - Merz,Michael, AU - Meier,Christoph, AU - Lewis,David, PY - 2017/5/17/pubmed PY - 2018/2/6/medline PY - 2017/5/17/entrez SP - 715 EP - 727 JF - Drug safety JO - Drug Saf VL - 40 IS - 8 N2 - 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 w = 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. SN - 1179-1942 UR - https://www.unboundmedicine.com/medline/citation/28508325/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_ L2 - https://dx.doi.org/10.1007/s40264-017-0541-2 DB - PRIME DP - Unbound Medicine ER -