Adverse drug reaction causality assessment tools for drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: room for improvement.

Creator(s)

Jennifer Goldman, Children's Mercy HospitalFollow
Wen-Hung Chung
Brian R. Lee, Children's Mercy HospitalFollow
Chun-Bing Chen
Chun-Wei Lu
Wolfram Hoetzenecker
Robert Micheletti
Sally Usdin Yasuda
David J. Margolis
Neil H. Shear
Jeffery P. Struewing
Munir Pirmohamed

Document Type

Article

Publication Date

8-2019

Identifier

DOI: 10.1007/s00228-019-02670-9; PMCID: PMC6659414

Abstract

PURPOSE: Establishment of causality between drug exposure and adverse drug reactions (ADR) is challenging even for serious ADRs such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Several causality assessment tools (CAT) exist, but the reliability and validity of such tools is variable. The objective of this study was to compare the reliability and validity of existing ADR CATs on SJS/TEN cases.

METHODS: Seven investigators completed three CAT (ALDEN, Naranjo, Liverpool) for 10 SJS/TEN cases. Each CAT categorized the causality of 30 potential drugs as definite/very probable, probable, possible, or doubtful/unlikely. An additional reviewer provided expert opinion by designating the implicated drug(s) for each case. A Kappa score was generated to compare CAT responses both by method (reliability of all 7 reviewers, by CATs) and by reviewer (reliability of the 3 CAT, by reviewer). A c statistic was calculated to assess validity.

RESULTS: Inter-rater reliability by CAT was poor to fair: ALDEN 0.22, Naranjo 0.11, and Liverpool 0.12. Reliability was highest when causality classification was definite/very probable (0.16-0.41). Similarly, intra-rater reliability by reviewer was poor. When comparing the validity of the overall CAT to expert reviewer, area under the curve was highest for ALDEN (c statistic 0.65) as compared to Liverpool (0.55) or Naranjo (0.54).

CONCLUSION: Available CAT have poor reliability and validity for drug-induced SJS/TEN. Due to the importance of determining ADR causality for research, industry, and regulatory purposes, development of an enhanced tool that can incorporate data from immunological testing and pharmacogenetic results may strengthen CAT usefulness and applicability for drug-induced SJS/TEN.

Journal Title

European journal of clinical pharmacology

Volume

75

Issue

8

First Page

1135

Last Page

1141

MeSH Keywords

Algorithms; Causality; Humans; Pharmacovigilance; Probability; Reproducibility of Results; Risk Assessment; Risk Factors; Stevens-Johnson Syndrome

Keywords

Adverse drug reactions; Causality assessment tool; Stevens-Johnson syndrome; Toxic epidermal necrolysis

Comments

Grant support

• KL2 TR000119/TR/NCATS NIH HHS/United States

Erratum in

• Correction to: Adverse drug reaction causality assessment tools for drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: room for improvement. Goldman JL, Chung WH, Lee BR, Chen CB, Lu CW, Hoetzenecker W, Micheletti R, Yasuda SU, Margolis DJ, Shear NH, Struewing JP, Pirmohamed M.Eur J Clin Pharmacol. 2019 Sep;75(9):1331. doi: 10.1007/s00228-019-02710-4.PMID: 31254013

Recommended Citation

Goldman JL, Chung WH, Lee BR, et al. Adverse drug reaction causality assessment tools for drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: room for improvement [published correction appears in Eur J Clin Pharmacol. 2019 Jun 29;:]. Eur J Clin Pharmacol. 2019;75(8):1135-1141. doi:10.1007/s00228-019-02670-9