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Hey-Hadavi J, Seekins D, Palmer M, et al. Overview of Causality Assessment for Drug-Induced Liver Injury (DILI) in Clinical Trials. Drug Saf. 2021;44(6):619-634doi: 10.1007/s40264-021-01051-5.
Hey-Hadavi, J., Seekins, D., Palmer, M., Coffey, D., Caminis, J., Abdullaev, S., Patwardhan, M., Tyler, H., Raheja, R., Stanley, A. M., Pineda-Salgado, L., Bourdet, D. L., Andrade, R. J., Hayashi, P. H., Dimick-Santos, L., Rockey, D. C., & Estilo, A. (2021). Overview of Causality Assessment for Drug-Induced Liver Injury (DILI) in Clinical Trials. Drug safety, 44(6), 619-634. https://doi.org/10.1007/s40264-021-01051-5
Hey-Hadavi, Juliana, et al. "Overview of Causality Assessment for Drug-Induced Liver Injury (DILI) in Clinical Trials." Drug safety vol. 44,6 (2021): 619-634. doi: https://doi.org/10.1007/s40264-021-01051-5
Hey-Hadavi J, Seekins D, Palmer M, Coffey D, Caminis J, Abdullaev S, Patwardhan M, Tyler H, Raheja R, Stanley AM, Pineda-Salgado L, Bourdet DL, Andrade RJ, Hayashi PH, Dimick-Santos L, Rockey DC, Estilo A. Overview of Causality Assessment for Drug-Induced Liver Injury (DILI) in Clinical Trials. Drug Saf. 2021 Jun;44(6):619-634. doi: 10.1007/s40264-021-01051-5. Epub 2021 Mar 16. PMID: 33725335; PMCID: PMC8184702.
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Drug Saf. 2021 Jun;44(6):619-634. doi: 10.1007/s40264-021-01051-5. Epub 2021 Mar 16.

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

Drug safety

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, Alvin Estilo

Affiliations

  1. Pfizer, 235 E 42nd Street, New York City, NY, 10017, USA. [email protected].
  2. Bristol-Myers Squibb, Lawrenceville, NJ, USA.
  3. Takeda, Cambridge, MA, USA.
  4. Liver Consulting LLC, New York City, USA.
  5. Sanofi, Bridgewater, NJ, USA.
  6. AbbVie, North Chicago, IL, USA.
  7. Otsuka Pharmaceutical Development and Commercialization, Inc., 508 Carnegie Center Dr, Princeton, NJ, 08540, USA.
  8. IQ DILI Consortium, Washington, DC, USA.
  9. Theravance Biopharma, South San Francisco, CA, USA.
  10. Unidad de Gestión Clínica de Aparato Digestivo, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas CIBERehd, Málaga, Spain.
  11. University of North Carolina, Chapel Hill, NC, USA.
  12. US Food and Drug Administration, Silver Spring, MD, USA.
  13. Medical University of South Carolina, Charleston, SC, USA.
  14. Otsuka Pharmaceutical Development and Commercialization, Inc., 508 Carnegie Center Dr, Princeton, NJ, 08540, USA. [email protected].

PMID: 33725335 PMCID: PMC8184702 DOI: 10.1007/s40264-021-01051-5

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.

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