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Agreement of expert judgment in causality assessment of adverse drug reactions

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Abstract

Background

Global introspection is, with operational algorithms and Bayes’ theorem, one of the three main approaches used to assess the causal relationship between a drug treatment and the occurrence of an adverse event.

Objective

To analyze and compare the judgments of five senior experts using global introspection about drug causation on a random set of putative adverse drug reactions.

Methods

A random sample of 150 drug-effect pairs was constituted. For each pair, five senior experts had to independently assess the probability of drug causation from 0 to 1 by using a 100 mm visual analog scale (VAS). For analysis, those probabilities were secondarily split into seven levels of causality: excluded (0–0.05); unlikely (0.06–0.25); doubtful (0.26–0.45); unassessable/unclassifiable (0.46–0.55); plausible (0.56–0.75); likely (0.75–0.95); and certain (0.95–1). Agreement among the five experts was assessed using kappa coefficients (κ).

Results

The overall agreement between experts was poor (κ=0.20), although significantly different from chance, and varied according to the level of causality. It was lower for the unlikely, doubtful, unassessable/unclassifiable, and plausible categories (κ=0.03, 0.03, −0.01, and 0.13, respectively) than for VAS extremes: excluded, likely, and certain (κ=0.40, 0.32, and 0.30, respectively).

Conclusion

This study confirms that experts express marked disagreements when assessing drug causality independently. The agreement rate was lower for intermediate levels of causality, especially when strong evidence was lacking for confirming or ruling out drug causality. Therefore, in a decision-making context, a step-by-step consensual approach such as the Delphi method seems necessary to make the assessment of such cases more reliable.

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Acknowledgements

This study was funded as a research project by a grant from the non-profit-making association, ARME-Pharmacovigilance (Bordeaux, France) and supported by the Agence Françoise de Sécurité Sanitaire des Produits de Santé. We gratefully acknowledge the contributions of Jacques Caron (Centre régional de Pharmacovigilance, Lille), Georges Lagier (Centre régional de Pharmacovigilance, Paris Fernand Widal), Louis Merle, (Centre régional de Pharmacovigilance, Limoges) and Thierry Vial (Centre régional de Pharmacovigilance, Lyon).

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Correspondence to Yannick Arimone.

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Arimone, Y., Bégaud, B., Miremont-Salamé, G. et al. Agreement of expert judgment in causality assessment of adverse drug reactions. Eur J Clin Pharmacol 61, 169–173 (2005). https://doi.org/10.1007/s00228-004-0869-2

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