Development and Inter-Rater Reliability of the Liverpool Adverse Drug Reaction Causality Assessment Tool

Ruairi M Gallagher,Jennifer R Mason,Anthony J Nunn,Rosalind L Smyth,Mark A Turner,Paula R Williamson,Jamie J Kirkham,Munir Pirmohamed,Kim A Bird,Antje Timmer

doi:10.1371/journal.pone.0028096

Ruairi M Gallagher, Jennifer R Mason + Show 8 more

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https://doi.org/10.1371/journal.pone.0028096

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Abstract

AimTo develop and test a new adverse drug reaction (ADR) causality assessment tool (CAT).MethodsA comparison between seven assessors of a new CAT, formulated by an expert focus group, compared with the Naranjo CAT in 80 cases from a prospective observational study and 37 published ADR case reports (819 causality assessments in total).Main Outcome Measures Utilisation of causality categories, measure of disagreements, inter-rater reliability (IRR).ResultsThe Liverpool ADR CAT, using 40 cases from an observational study, showed causality categories of 1 unlikely, 62 possible, 92 probable and 125 definite (1, 62, 92, 125) and ‘moderate’ IRR (kappa 0.48), compared to Naranjo (0, 100, 172, 8) with ‘moderate’ IRR (kappa 0.45). In a further 40 cases, the Liverpool tool (0, 66, 81, 133) showed ‘good’ IRR (kappa 0.6) while Naranjo (1, 90, 185, 4) remained ‘moderate’.ConclusionThe Liverpool tool assigns the full range of causality categories and shows good IRR. Further assessment by different investigators in different settings is needed to fully assess the utility of this tool.

Highlights

Adverse drug reactions are a frequent source of morbidity and mortality [1,2]
The Liverpool tool assigns the full range of causality categories and shows good inter-rater reliability (IRR)
These criteria were not meant for adverse drug reaction (ADR), the elements have been adapted in ADR causality tools

Summary

Introduction

Adverse drug reactions are a frequent source of morbidity and mortality [1,2]. Causality assessment of ADRs may be undertaken by clinicians, academics, pharmaceutical industry, regulators and in different settings, including clinical trials [3,4,5,6]. Bradford Hill set out criteria for establishing causality which included assessment of strength of the association, consistency of the association, specificity, temporal relationship, biological gradient (dose response), biological plausibility, coherence, experimental evidence, and reasoning by analogy. These criteria were not meant for ADRs, the elements have been adapted in ADR causality tools. It is known that assessing ADR likelihood without a structure can lead to wide disagreements between assessors [12] These disagreements may be the result of differing clinical backgrounds, specialties and experience. A large number of causality tools have been developed ranging from the simple to the complex, but none have gained universal acceptance [13]

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