The Impact of COVID-19 and COVID-19 Vaccination on Detection, Assessment, and Management of Suspected Acute Drug-Induced Liver Injury Occurring during Clinical Trials: Consensus Recommendations from the IQ DILI Initiative.
Melissa Palmer, Daniel Seekins, Mark Avigan, John Marcinak, Don C Rockey, Arie Regev, Vineet K Shastri, James H Lewis, Ajit Dash
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引用次数: 0
Abstract
While the acute impact of the coronavirus disease 2019 (COVID-19) pandemic has waned, implications for clinical trials remain. In particular, guidance for evaluation of elevated liver tests due to COVID-19, its treatments, and COVID-19 vaccination is lacking. The IQ DILI Initiative, composed of experts from academia, regulatory agencies, and industry herein propose recommendations to address this gap. Extensive literature review was conducted and structured discussions were held between IQ DILI industry members, regulators, and academic experts in hepatology and DILI. Liver-related manifestations in nonhospitalized patients with COVID-19 are highly varied. Evidence of liver injury may occur after COVID-19 symptoms resolve and testing is negative. Treatments for COVID-19 may cause liver injury or alter pharmacokinetics. COVID-19 vaccination has been associated with rare but clear hepatotoxicity, typically consistent with drug-induced autoimmune-like hepatitis, although other presentations, severity, latency, and time to resolution have been reported. Liver injury occurred with mRNA and viral vector vaccines, and in individuals with and without underlying autoimmune or liver diseases. Drug developers and investigators should be aware of the potential liver-related manifestations related to COVID-19, its treatments, and COVID-19 vaccination, as this may impact study eligibility and causality assessment during a trial. COVID-19 testing should be considered part of DILI causality assessment, as a positive test may prevent premature termination of the investigational drug. Since clinical trial participants may not consider vaccinations in their medical history, specific inquiry about their receipt is important when liver tests are abnormal during screening and as part of DILI causality assessment.
期刊介绍：
Drug Safety is the official journal of the International Society of Pharmacovigilance. The journal includes:
Overviews of contentious or emerging issues.
Comprehensive narrative reviews that provide an authoritative source of information on epidemiology, clinical features, prevention and management of adverse effects of individual drugs and drug classes.
In-depth benefit-risk assessment of adverse effect and efficacy data for a drug in a defined therapeutic area.
Systematic reviews (with or without meta-analyses) that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement.
Original research articles reporting the results of well-designed studies in disciplines such as pharmacoepidemiology, pharmacovigilance, pharmacology and toxicology, and pharmacogenomics.
Editorials and commentaries on topical issues.
Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in Drug Safety Drugs may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand important medical advances.
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