Inter-expert agreement of seven criteria in causality assessment of adverse drug reactions
Inter-expert agreement of seven criteria in causality assessment of adverse drug reactions
复制标题
DOI：
10.1111/j.1365-2125.2007.02937.x
复制
发表时间：
2007-10-01
影响因子：
3.4
通讯作者：
Begaud, Bernard
中科院分区：
文献类型：
--
作者：
Arimone, Yannick;Miremont-Salame, Ghada;Begaud, Bernard
在药物警戒中，已经提出了许多方法来评估药物不良反应的因果关系。专家判断通常用于评估药物治疗与不良事件发生之间的因果关系。这种形式的判断依赖于明确或隐含的因果关系标准。这项研究补充说：我们的研究比较了五位资深专家使用全球内省对药物因果关系的判断和七个因果关系标准对一组随机的假定药物不良反应的判断。即使以前的出版物显示专家之间使用全球内省的一致性很差，很少有人比较训练有素的药理学家的判断，熟悉使用标准化因果关系评估方法，评价5名资深专家在评估7项因果关系标准时的一致性和药物因果关系的可能性。对于每一对，五位专家分别评估了（i）药物因果关系的概率，其次分为七个因果关系水平：排除（0-0.05），不太可能（0.06-0.25）、可疑（0.26-0.45）、不确定（0.46-0.55）、合理（0.56-0.75）、可能（0.76-0.95）和确定（0.96-1）;和（ii）7个因果关系标准。为了检验专家之间的差异，使用了kappa指数。五位专家对药物因果关系概率的一致性非常差（kappa = 0.05）。在七个因果关系水平中，只有“可疑”显示出显著的一致率（kappa = 0.32，P < 0.001）。对于所有标准，kappa指数均具有显著性，但“风险因素"项除外（kappa = 0.09）。仅在“用药部位反应或药物毒性血浆浓度或验证试验”标准方面，专家之间的一致性良好（0.64，P < 0.001）。然而，与因果关系标准的Kappa指数的一致率范围为0.12至0.38。本研究证实，在没有操作程序的情况下，专家之间的一致性很低。在设计因果关系评估方法时应考虑这一点。特别是，应降低导致低水平一致的标准的权重。
What is already known about this subjectIn pharmacovigilance, many methods have been proposed for causality assessment of adverse drug reactions.Expert judgement is commonly used to evaluate the causal relationship between a drug treatment and the occurrence of an adverse event. This form of judgement relies either explicitly or implicitly on causality criteria.What this study addsOur study compares the judgements of five senior experts using global introspection about drug causation and seven causality criteria on a random set of putative adverse drug reactions.Even if previous publications have shown poor agreement between experts using global introspection, few have compared judgements of well trained pharmacologists, familiar with using a standardized causality assessment method.To evaluate agreement between five senior experts when assessing seven causality criteria and the probability of drug causation.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.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.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.