Food and Drug Administration, Silver Spring, Maryland, USA.
Servicio de Aparato Digestivo y de Farmacología Clínica, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga-IBIMA, Facultad de Medicina, Universidad de Málaga, Málaga, Spain.
Hepatology. 2022 Jul;76(1):18-31. doi: 10.1002/hep.32327. Epub 2022 Mar 22.
Roussel Uclaf Causality Assessment Method (RUCAM) for DILI has been hindered by subjectivity and poor reliability. We sought to improve the RUCAM using data from the Drug-Induced Liver Injury Network (DILIN) and the Spanish DILI Registry, published literature, and iterative computer modeling.
RUCAM criteria were updated, clarified, and computerized. We removed criteria 3 (risk factors) for lack of added value and criteria 4 because we felt it more useful to assess each drug separately. Criteria 6 (drug-specific risk) was anchored to LiverTox likelihood scores. Iterative testing in subsets of 50-100 single-agent, nonherbal cases from both registries was done to optimize performance. We used classification tree analysis to establish diagnostic cutoffs for this revised electronic causality assessment method (RECAM) and compared RECAM with RUCAM for correlation with expert opinion diagnostic categories in 194 DILI cases (98 DILIN, 96 Spanish DILI). Area under receiver operator curves for identifying at least probable DILI were the same at 0.89 for RECAM and RUCAM. However, RECAM diagnostic categories have better observed overall agreement with expert opinion (0.62 vs. 0.56 weighted kappa, p = 0.14), and had better sensitivity to detect extreme diagnostic categories (73 vs. 54 for highly likely or high probable, p = 0.02; 65 vs. 48 for unlikely/excluded, p = 0.08) than RUCAM diagnostic categories.
RECAM is an evidence-based update that is at least as capable as RUCAM in diagnosing DILI compared with expert opinion but is better than RUCAM at the diagnostic extremes. RECAM's increased objectivity and clarity will improve precision, reliability, and standardization of DILI diagnosis, but further refinement and validation in other cohorts are needed.
鲁塞尔乌克拉夫因果评估方法（RUCAM）用于药物性肝损伤（DILI）的评估存在主观性和可靠性差的问题。我们试图通过药物性肝损伤网络（DILIN）和西班牙 DILI 登记处、已发表文献以及迭代计算机建模的数据来改进 RUCAM。
更新、澄清和计算机化了 RUCAM 标准。我们删除了标准 3（危险因素），因为其缺乏附加价值，并且删除了标准 4，因为我们认为单独评估每种药物更有用。标准 6（药物特异性风险）锚定在 LiverTox 可能性评分上。在两个登记处的 50-100 例单一药物、非草药案例的子集中进行迭代测试，以优化性能。我们使用分类树分析为这个修订后的电子因果评估方法（RECAM）建立诊断截止值，并在 194 例 DILI 病例（98 例 DILIN，96 例西班牙 DILI）中比较 RECAM 与 RUCAM 与专家意见诊断类别之间的相关性。识别至少可能的 DILI 的受试者工作特征曲线下面积对于 RECAM 和 RUCAM 来说相同，均为 0.89。然而，RECAM 诊断类别与专家意见的总体一致性更好（加权kappa，0.62 对 0.56，p=0.14），并且对检测极端诊断类别（高度可能或很可能为 73 对 54，p=0.02；不太可能/排除为 65 对 48，p=0.08）的敏感性更好。
RECAM 是一种基于证据的更新，与专家意见相比，它在诊断 DILI 方面至少与 RUCAM 一样有效，但在诊断极端方面优于 RUCAM。RECAM 的客观性和清晰度的提高将提高 DILI 诊断的准确性、可靠性和标准化，但需要在其他队列中进一步完善和验证。
