Rochon James, Protiva Petr, Seeff Leonard B, Fontana Robert J, Liangpunsakul Suthat, Watkins Paul B, Davern Timothy, McHutchison John G
Duke Clinical Research Institute, Durham, NC 27713, USA.
Hepatology. 2008 Oct;48(4):1175-83. doi: 10.1002/hep.22442.
The Roussel Uclaf Causality Assessment Method (RUCAM) was developed to quantify the strength of association between a liver injury and the medication implicated as causing the injury. However, its reliability in a research setting has never been fully explored. The aim of this study was to determine test-retest and interrater reliabilities of RUCAM in retrospectively-identified cases of drug induced liver injury. The Drug-Induced Liver Injury Network is enrolling well-defined cases of hepatotoxicity caused by isoniazid, phenytoin, clavulanate/amoxicillin, or valproate occurring since 1994. Each case was adjudicated by three reviewers working independently; after an interval of at least 5 months, cases were readjudicated by the same reviewers. A total of 40 drug-induced liver injury cases were enrolled including individuals treated with isoniazid (nine), phenytoin (five), clavulanate/amoxicillin (15), and valproate (11). Mean +/- standard deviation age at protocol-defined onset was 44.8 +/- 19.5 years; patients were 68% female and 78% Caucasian. Cases were classified as hepatocellular (44%), mixed (28%), or cholestatic (28%). Test-retest differences ranged from -7 to +8 with complete agreement in only 26% of cases. On average, the maximum absolute difference among the three reviewers was 3.1 on the first adjudication and 2.7 on the second, although much of this variability could be attributed to differences between the enrolling investigator and the external reviewers. The test-retest reliability by the same assessors was 0.54 (upper 95% confidence limit = 0.77); the interrater reliability was 0.45 (upper 95% confidence limit = 0.58). Categorizing the RUCAM to a five-category scale improved these reliabilities but only marginally.
The mediocre reliability of the RUCAM is problematic for future studies of drug-induced liver injury. Alternative methods, including modifying the RUCAM, developing drug-specific instruments, or causality assessment based on expert opinion, may be more appropriate.
鲁塞尔·优克福因果关系评估方法（RUCAM）旨在量化肝损伤与被认为导致该损伤的药物之间关联的强度。然而，其在研究环境中的可靠性从未得到充分探究。本研究的目的是确定RUCAM在回顾性确定的药物性肝损伤病例中的重测信度和评分者间信度。药物性肝损伤网络正在招募自1994年以来由异烟肼、苯妥英、克拉维酸/阿莫西林或丙戊酸引起的明确的肝毒性病例。每个病例由三名独立工作的评审员进行判定；间隔至少5个月后，由相同的评审员重新判定。共纳入40例药物性肝损伤病例，包括接受异烟肼治疗的个体（9例）、苯妥英（5例）、克拉维酸/阿莫西林（15例）和丙戊酸（11例）。方案定义的发病时的平均年龄±标准差为44.8±19.5岁；患者中68%为女性，78%为白种人。病例分为肝细胞型（44%）、混合型（28%）或胆汁淤积型（28%）。重测差异范围为 -7至 +8，仅26%的病例完全一致。平均而言，三名评审员之间的最大绝对差异在首次判定时为3.1，第二次判定时为2.7，尽管这种变异性很大程度上可归因于招募研究者与外部评审员之间的差异。同一评估者的重测信度为0.54（95%置信上限 = 0.77）；评分者间信度为0.45（95%置信上限 = 0.58）。将RUCAM分类为五类量表可提高这些信度，但幅度很小。
RUCAM的中等信度对未来药物性肝损伤研究存在问题。替代方法，包括修改RUCAM、开发药物特异性工具或基于专家意见的因果关系评估，可能更合适。
