Inter-expert agreement of seven criteria in causality assessment of adverse drug reactions.
OBJECTIVE
To evaluate agreement between five senior experts when assessing seven causality criteria and the probability of drug causation.


METHODS
A sample of 31 adverse event-drug pairs was constituted. For each pair, five experts separately assessed (i) the probability of drug causation, which was secondarily divided into seven causality levels: ruled out (0-0.05), unlikely (0.06-0.25), doubtful (0.26-0.45), indeterminate (0.46-0.55), plausible (0.56-0.75), likely (0.76-0.95), and certain (0.96-1); and (ii) seven causality criteria. To test discrepancies between experts, the kappa index was used.


RESULTS
The agreement of the five experts was very poor (kappa = 0.05) for the probability of drug causation. Among the seven levels of causality, only 'doubtful' showed a significant rate of agreement (kappa = 0.32, P < 0.001). For all criteria, the kappa index was significant except for the item 'risk(s) factor(s)' (kappa = 0.09). Agreement between experts was good (0.64, P < 0.001) only for the criterion 'reaction at site of application or toxic plasma concentration of the drug or validated test'. However, the rate of agreement with kappa indices of the causality criteria ranged from 0.12 to 0.38.


CONCLUSIONS
This study confirms that in the absence of an operational procedure, agreement between experts is low. This should be considered when designing a causality assessment method. In particular, criteria inducing a low level of agreement should have their weight reduced.
Arimone
Yannick
Y
INSERM U 657, Département de Pharmacologie, Université Victor Segalen, Bordeaux 2, France. yannick.arimone@etud.u-bordeaux2.fr
Miremont-Salamé
Ghada
G
Haramburu
Françoise
F
Molimard
Mathieu
M
Moore
Nicholas
N
Fourrier-Réglat
Annie
A
Bégaud
Bernard
B
D016907:Adverse Drug Reaction Reporting Systems; D015984:Causality; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D015588:Observer Variation; D011336:Probability
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