Evaluation of Naranjo Adverse Drug Reactions Probability Scale in causality assessment of drug‐induced liver injury

Abstract

Summary: Background Causality assessment in hepatotoxicity is challenging. The current standard liver‐specific Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale is complex and difficult to implement in daily practice. The Naranjo Adverse Drug Reactions Probability Scale is a simple and widely used nonspecific scale, which has not been specifically evaluated in drug‐induced liver injury. Aim To compare the Naranjo method with the standard liver‐specific Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale in evaluating the accuracy and reproducibility of Naranjo Adverse Drug Reactions Probability Scale in the diagnosis of hepatotoxicity. Methods Two hundred and twenty‐five cases of suspected hepatotoxicity submitted to a national registry were evaluated by two independent observers and assessed for between‐observer and between‐scale differences using percentages of agreement and the weighted kappa (κ w) test. Results A total of 249 ratings were generated. Between‐observer agreement was 45% with a κ w value of 0.17 for the Naranjo Adverse Drug Reactions Probability Scale, while there was a higher agreement when using the Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale (72%, κ w: 0.71). Concordance between the two scales was 24% (κ w: 0.15). The Naranjo Adverse Drug Reactions Probability Scale had low sensitivity (54%) and poor negative predictive value (29%) and showed a limited capability to distinguish between adjacent categories of probability. Conclusion The Naranjo scale lacks validity and reproducibility in the attribution of causality in hepatotoxicity.