Reliability of the roussel uclaf causality assessment method for assessing causality in drug-induced liver injury

James Rochon, Petr Protiva, Leonard B. Seeff, Robert J. Fontana, Suthat Liangpunsakul, Paul B. Watkins, Timothy Davern, John G. McHutchison

Research output: Contribution to journalArticle

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Abstract

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-de.ned 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)1175-1183
Number of pages9
JournalHepatology
Volume48
Issue number4
DOIs
StatePublished - Oct 2008

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Chemical and Drug Induced Liver Injury
Causality
Clavulanic Acid
Amoxicillin
Isoniazid
Valproic Acid
Phenytoin
Reproducibility of Results
Wounds and Injuries
Expert Testimony
Research Personnel
Liver
Research
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Hepatology
  • Medicine(all)

Cite this

Rochon, J., Protiva, P., Seeff, L. B., Fontana, R. J., Liangpunsakul, S., Watkins, P. B., ... McHutchison, J. G. (2008). Reliability of the roussel uclaf causality assessment method for assessing causality in drug-induced liver injury. Hepatology, 48(4), 1175-1183. https://doi.org/10.1002/hep.22442

Reliability of the roussel uclaf causality assessment method for assessing causality in drug-induced liver injury. / Rochon, James; Protiva, Petr; Seeff, Leonard B.; Fontana, Robert J.; Liangpunsakul, Suthat; Watkins, Paul B.; Davern, Timothy; McHutchison, John G.

In: Hepatology, Vol. 48, No. 4, 10.2008, p. 1175-1183.

Research output: Contribution to journalArticle

Rochon, J, Protiva, P, Seeff, LB, Fontana, RJ, Liangpunsakul, S, Watkins, PB, Davern, T & McHutchison, JG 2008, 'Reliability of the roussel uclaf causality assessment method for assessing causality in drug-induced liver injury', Hepatology, vol. 48, no. 4, pp. 1175-1183. https://doi.org/10.1002/hep.22442
Rochon, James ; Protiva, Petr ; Seeff, Leonard B. ; Fontana, Robert J. ; Liangpunsakul, Suthat ; Watkins, Paul B. ; Davern, Timothy ; McHutchison, John G. / Reliability of the roussel uclaf causality assessment method for assessing causality in drug-induced liver injury. In: Hepatology. 2008 ; Vol. 48, No. 4. pp. 1175-1183.
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