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. 2017 Jan 3;12(1):e0169393.
doi: 10.1371/journal.pone.0169393. eCollection 2017.

Development of the Liverpool Adverse Drug Reaction Avoidability Assessment Tool

Free PMC article

Development of the Liverpool Adverse Drug Reaction Avoidability Assessment Tool

Louise E Bracken et al. PLoS One. .
Free PMC article


Aim: To develop and test a new tool to assess the avoidability of adverse drug reactions that is suitable for use in paediatrics but which is also applicable to a variety of other settings.

Methods: The study involved multiple phases. Preliminary work involved using the Hallas scale and a modification of the existing Hallas scale, to assess two different sets of adverse drug reaction (ADR) case reports. Phase 1 defined, modified and refined a new tool using multidisciplinary teams. Phase 2 involved the assessment of 50 ADR case reports from a prospective study of paediatric inpatients by individual assessors. Phase 3 compared assessments with the new tool for individuals and groups in comparison to the 'gold standard' (the avoidability outcome set by a panel of senior investigators: an experienced clinical pharmacologist, paediatrician and pharmacist).

Main outcome measures: Inter-rater reliability (IRR), measure of disagreement and utilization of avoidability categories.

Results: Preliminary work-Pilot phase: results for the original Hallas cases were fair and pairwise kappa scores ranged from 0.21 to 0.36. Results for the modified Hallas cases were poor, pairwise kappa scores ranged from 0.06 to 0.16. Phase 1: on initial use of the new tool, agreement between the two multidisciplinary groups was found on 13/20 cases with a kappa score of 0.29 (95% CI -0.04 to 0.62). Phase 2: the assessment of 50 ADR case reports by six individual reviewers yielded pairwise kappa scores ranging from poor to good 0.12 to 0.75 and percentage exact agreement (%EA) ranged from 52-90%. Phase 3: Percentage exact agreement ranged from 35-70%. Overall, individuals had better agreement with the 'gold standard'.

Conclusion: Avoidability assessment is feasible but needs careful attention to methods. The Liverpool ADR avoidability assessment tool showed mixed IRR. We have developed and validated a method for assessing the avoidability of ADRs that is transparent, more objective than previous methods and that can be used by individuals or groups.

Conflict of interest statement

Professor Munir Pirmohamed is a member of the Comission on Human Medicines and Chairs the Pharmacovigilance Expert Advisory Group. Munir Pirmohamed and Professor Rosalind Smyth are NIHR Senior Investigators. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The other authors declare they have no competing interests.


Fig 1
Fig 1. Hallas and the modified Hallas scale.
Fig 2
Fig 2. Flow chart of the development of the Liverpool ADR avoidability assesmsent tool.
Fig 3
Fig 3. The Liverpool ADR avoidability assessment tool (LAAT).

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