Overview of Causality Assessment for Drug-Induced Liver Injury (DILI) in Clinical Trials

Juliana Hey-Hadavi (), Daniel Seekins, Melissa Palmer, Denise Coffey, John Caminis, Sandzhar Abdullaev, Meenal Patwardhan, Haifa Tyler, Ritu Raheja, Ann Marie Stanley, Liliam Pineda-Salgado, David L. Bourdet, Raul J. Andrade, Paul H. Hayashi, Lara Dimick-Santos, Don C. Rockey and Alvin Estilo ()
Additional contact information
Juliana Hey-Hadavi: Pfizer
Daniel Seekins: Bristol-Myers Squibb
Melissa Palmer: Takeda
Denise Coffey: Bristol-Myers Squibb
John Caminis: Sanofi
Sandzhar Abdullaev: Bristol-Myers Squibb
Meenal Patwardhan: AbbVie
Haifa Tyler: Otsuka Pharmaceutical Development and Commercialization, Inc.
Ritu Raheja: AbbVie
Ann Marie Stanley: IQ DILI Consortium
Liliam Pineda-Salgado: Otsuka Pharmaceutical Development and Commercialization, Inc.
David L. Bourdet: Theravance Biopharma
Raul J. Andrade: Universidad de Málaga, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas CIBERehd
Paul H. Hayashi: University of North Carolina
Lara Dimick-Santos: US Food and Drug Administration
Don C. Rockey: Medical University of South Carolina
Alvin Estilo: Otsuka Pharmaceutical Development and Commercialization, Inc.

Drug Safety, 2021, vol. 44, issue 6, No 2, 619-634

Abstract: Abstract Causality assessment for suspected drug-induced liver injury (DILI) during drug development and following approval is challenging. The IQ DILI Causality Working Group (CWG), in collaboration with academic and regulatory subject matter experts (SMEs), developed this manuscript with the following objectives: (1) understand and describe current practices; (2) evaluate the utility of new tools/methods/practice guidelines; (3) propose a minimal data set needed to assess causality; (4) define best practices; and (5) promote a more structured and universal approach to DILI causality assessment for clinical development. To better understand current practices, the CWG performed a literature review, took a survey of member companies, and collaborated with SMEs. Areas of focus included best practices for causality assessment during clinical development, utility of adjudication committees, and proposals for potential new avenues to improve causality assessment. The survey and literature review provided renewed understanding of the complexity and challenges of DILI causality assessment as well as the use of non-standardized approaches. Potential areas identified for consistency and standardization included role and membership of adjudication committees, standardized minimum dataset, updated assessment tools, and best practices for liver biopsy and rechallenge in the setting of DILI. Adjudication committees comprised of SMEs (i.e., utilizing expert opinion) remain the standard for DILI causality assessment. A variety of working groups continue to make progress in pursuing new tools to assist with DILI causality assessment. The minimum dataset deemed adequate for causality assessment provides a path forward for standardization of data collection in the setting of DILI. Continued progress is necessary to optimize and advance innovative tools necessary for the scientific, pharmaceutical, and regulatory community.

Date: 2021
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
http://link.springer.com/10.1007/s40264-021-01051-5 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:spr:drugsa:v:44:y:2021:i:6:d:10.1007_s40264-021-01051-5

Ordering information: This journal article can be ordered from
http://www.springer.com/adis/journal/40264

DOI: 10.1007/s40264-021-01051-5

Access Statistics for this article

Drug Safety is currently edited by Nitin Joshi

More articles in Drug Safety from Springer
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().