Causality assessment of adverse reactions to drugs--I. A novel method based on the conclusions of international consensus meetings: application to drug-induced liver injuries.
Despite the great number of methods proposed, assessing the causal role of a drug in the occurrence of an adverse medical event remains one of the most controversial issues. Qualifying terms for criteria, such as "compatible", "suggestive" of "inconclusive", have never been strictly defined, leading to low reproducibility. Weights of the criteria are usually not adapted to the injured organ, decreasing the specificity of the method. In this paper, a new method for drug causality assessment is described. Contents and limits of the criteria have been defined by experts convened to organ-oriented international consensus meetings. Additional criteria have been introduced and weights attributed. The method was applied to reports of acute liver injuries. The reproducibility was tested by an independent team. The validity of this novel method is studied in the following paper, based on an original approach using reports with positive rechallenge as external standard.
Danan
G
G
International Drug Safety Department, Roussel UCLAF, Paris, France.
Benichou
C
C
D000367:Age Factors; D000428:Alcohol Drinking; D015984:Causality; D003245:Consensus Statements as Topic; D004359:Drug Therapy, Combination; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006525:Hepatitis, Viral, Human / Q000150:complications; D006801:Humans; D008099:Liver / Q000187:drug effects*; D008875:Middle Aged; D011247:Pregnancy; D015203:Reproducibility of Results; D012307:Risk Factors; D013997:Time Factors