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. 2011;6(12):e28096.
doi: 10.1371/journal.pone.0028096. Epub 2011 Dec 14.

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

Free PMC article

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

Ruairi M Gallagher et al. PLoS One. .
Free PMC article


Aim: To develop and test a new adverse drug reaction (ADR) causality assessment tool (CAT).

Methods: A 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).

Results: The 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'.

Conclusion: The 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.

Conflict of interest statement

Competing Interests: RLS and MP are members of the Commission on Human Medicines. MP Chairs the Pharmacovigilance Expert Advisory Group, while RLS Chairs the Paediatric Medicines Expert Advisory Group.


Figure 1
Figure 1. Flowchart of the development of the Liverpool ADR Causality Assessment Tool.
Figure 2
Figure 2. Liverpool ADR causality assessment tool.

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