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Methods for Causality Assessment of Adverse Drug Reactions

A Systematic Review

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Abstract

Numerous methods for causality assessment of adverse drug reactions (ADRs) have been published. The aim of this review is to provide an overview of these methods and discuss their strengths and weaknesses. We conducted electronic searches in MEDLINE (via PubMed), EMBASE and the Cochrane databases to find all assessment methods. Thirty-four different methods were found, falling into three broad categories: expert judgement/global introspection, algorithms and probabilistic methods (Bayesian approaches). Expert judgements are individual assessments based on previous knowledge and experience in the field using no standardized tool to arrive at conclusions regarding causality. Algorithms are sets of specific questions with associated scores for calculating the likelihood of a cause-effect relationship. Bayesian approaches use specific findings in a case to transform the prior estimate of probability into a posterior estimate of probability of drug causation. The prior probability is calculated from epidemiological information and the posterior probability combines this background information with the evidence in the individual case to come up with an estimate of causation. As a result of problems of reproducibility and validity, no single method is universally accepted. Different causality categories are adopted in each method, and the categories are assessed using different criteria. Because assessment methods are also not entirely devoid of individual judgements, inter-rater reliability can be low. In conclusion, there is still no method universally accepted for causality assessment of ADRs.

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Acknowledgements

No sources of funding were used to assist in the preparation of this review. T.B. Agbabiaka and J. Savovic have both been supported by research fellowships sponsored by Dr Willmar Schwabe Pharmaceuticals, Germany. The authors have no conflicts of interest that are directly relevant to the contents of this review.

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Authors and Affiliations

  1. Complementary Medicine, Peninsula Medical School, Universities of Exeter and Plymouth, 25 Victoria Park Road, Exeter, EX2 4NT, UK

    Taofikat B. Agbabiaka & Edzard Ernst

  2. Department of Social Medicine, University of Bristol, Bristol, UK

    Jelena Savović

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  1. Taofikat B. Agbabiaka
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Correspondence to Taofikat B. Agbabiaka.

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Agbabiaka, T.B., Savović, J. & Ernst, E. Methods for Causality Assessment of Adverse Drug Reactions. Drug-Safety 31, 21–37 (2008). https://doi.org/10.2165/00002018-200831010-00003

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