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Causality assessment for suspected DILI during clinical phases of drug development.
Drug Saf. 2014 Nov; 37 Suppl 1:S47-56.DS

Abstract

Causality assessment is a critical step in establishing the diagnosis of drug induced liver injury (DILI) during drug development. DILI may resemble almost any type of liver disease, and often presents a serious challenge to clinical investigators and drug makers. The diagnosis of DILI is largely based upon a combination of a compatible clinical course, exclusion of all other reasonable causes, resemblance of clinical and pathological features to known features of liver injury due to the drug (i.e., "drug's signature"), and incidence of liver injury among patients treated with the drug compared to placebo or comparator. Causality assessment for suspected DILI is currently performed using either evaluation by physicians with expertise in liver disorders (i.e., expert opinion) or standardized scoring instruments such as the Roussel Uclaf Causality Assessment Method (RUCAM). Both approaches are widely used in the post marketing setting. Causality assessment based on expert opinion is considered superior to standardized instruments such as RUCAM, in the setting of drug development, and is currently the preferred approach during clinical trials. There is a need for a systematic revision of RUCAM that will render it more suitable for the setting of clinical trials and drug development. Careful monitoring and meticulous data collection during clinical trials are essential in all cases with established liver injury to allow for a proper causality assessment. A workshop was convened to discuss best practices for the assessment of drug-induced liver injury (DILI) in clinical trials. This publication is based on the conclusions of this workshop.

Authors+Show Affiliations

Global Patient Safety, Eli Lilly and Company, Lilly Corporate Center, Drop Code 2121, Indianapolis, IN, 46285, USA, regev_arie@lilly.com.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

25352327

Citation

Regev, Arie, et al. "Causality Assessment for Suspected DILI During Clinical Phases of Drug Development." Drug Safety, vol. 37 Suppl 1, 2014, pp. S47-56.
Regev A, Seeff LB, Merz M, et al. Causality assessment for suspected DILI during clinical phases of drug development. Drug Saf. 2014;37 Suppl 1:S47-56.
Regev, A., Seeff, L. B., Merz, M., Ormarsdottir, S., Aithal, G. P., Gallivan, J., & Watkins, P. B. (2014). Causality assessment for suspected DILI during clinical phases of drug development. Drug Safety, 37 Suppl 1, S47-56. https://doi.org/10.1007/s40264-014-0185-4
Regev A, et al. Causality Assessment for Suspected DILI During Clinical Phases of Drug Development. Drug Saf. 2014;37 Suppl 1:S47-56. PubMed PMID: 25352327.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Causality assessment for suspected DILI during clinical phases of drug development. AU - Regev,Arie, AU - Seeff,Leonard B, AU - Merz,Michael, AU - Ormarsdottir,Sif, AU - Aithal,Guruprasad P, AU - Gallivan,Jim, AU - Watkins,Paul B, PY - 2014/10/30/entrez PY - 2014/10/30/pubmed PY - 2015/6/30/medline SP - S47 EP - 56 JF - Drug safety JO - Drug Saf VL - 37 Suppl 1 N2 - Causality assessment is a critical step in establishing the diagnosis of drug induced liver injury (DILI) during drug development. DILI may resemble almost any type of liver disease, and often presents a serious challenge to clinical investigators and drug makers. The diagnosis of DILI is largely based upon a combination of a compatible clinical course, exclusion of all other reasonable causes, resemblance of clinical and pathological features to known features of liver injury due to the drug (i.e., "drug's signature"), and incidence of liver injury among patients treated with the drug compared to placebo or comparator. Causality assessment for suspected DILI is currently performed using either evaluation by physicians with expertise in liver disorders (i.e., expert opinion) or standardized scoring instruments such as the Roussel Uclaf Causality Assessment Method (RUCAM). Both approaches are widely used in the post marketing setting. Causality assessment based on expert opinion is considered superior to standardized instruments such as RUCAM, in the setting of drug development, and is currently the preferred approach during clinical trials. There is a need for a systematic revision of RUCAM that will render it more suitable for the setting of clinical trials and drug development. Careful monitoring and meticulous data collection during clinical trials are essential in all cases with established liver injury to allow for a proper causality assessment. A workshop was convened to discuss best practices for the assessment of drug-induced liver injury (DILI) in clinical trials. This publication is based on the conclusions of this workshop. SN - 1179-1942 UR - https://www.unboundmedicine.com/medline/citation/25352327/Causality_assessment_for_suspected_DILI_during_clinical_phases_of_drug_development_ L2 - https://dx.doi.org/10.1007/s40264-014-0185-4 DB - PRIME DP - Unbound Medicine ER -