Similarity and consistency assessment of three major online drug-drug interaction resources.

Aims: The aim of this study was to explore the level of agreement on drug-drug interaction (DDI) information listed in three major online drug information resources (DIRs) in terms of: (1) interacting drug pairs; (2) severity rating; (3) evidence rating; and (4) clinical management recommendations.

Methods: We extracted information from the British National Formulary (BNF), Thesaurus and Micromedex. Following drug name normalisation, we estimated the overlap of the DIRs in terms of DDI.

A reference set of clinically relevant adverse drug-drug interactions.

The accurate and timely detection of adverse drug-drug interactions (DDIs) during the postmarketing phase is an important yet complex task with potentially major clinical implications. The development of data mining methodologies that scan healthcare databases for drug safety signals requires appropriate reference sets for performance evaluation. Methodologies for establishing DDI reference sets are limited in the literature, while there is no publicly available resource simultaneously focusing on clinical relevance of DDIs and individual behaviour of interacting drugs.

QT Prolongation Risk Assessment in Oncology: Lessons Learned From Small-Molecule New Drug Applications Approved During 2011-2019.

The International Conference on Harmonisation (ICH) E14 guidance provides recommendations to assess the potential of a drug to delay cardiac repolarization (QT prolongation), including general guidelines for cases in which a conventional thorough QT study (TQT) might not be feasible. These guidelines have been updated through the ICH question-and-answer process, with the last revision in 2015. We conducted a comprehensive analysis of QT prolongation evaluation of small-molecule new drug applications (NDAs) approved in oncology between 2011 and 2019 to extract learning experience.

Urinary Kidney Biomarker Panel Detects Preclinical Antisense Oligonucleotide-Induced Tubular Toxicity.

Sensitive kidney safety assessment is important for successful drug development in both preclinical and clinical stages. The Food and Drug Administration recently qualified a composite measure of 6 urine creatinine-normalized biomarkers, such as clusterin, cystatin C, kidney injury molecule 1 (KIM-1), N-acetyl-β-d-glucosaminidase, neutrophil gelatinase-associated lipocalin (NGAL), and osteopontin, for monitoring kidney toxicity in early clinical trials. The qualification was based on small molecule drugs in humans, and the full panel has not been assessed in other species or for other drug modalities.

Are Laboratory Parameter (Biomarker) Values Similar to the Healthy Volunteer Reference Range in Individuals with Diabetes.

Background: Identification of laboratory parameter clinical safety signals depends on the terminology and scoring criteria. Grade 1 scoring criteria in the Common Terminology Criteria for Adverse Events (CTCAE) is typically based on the healthy volunteer reference range (HVRR). The objectives of this study were to determine 1) what laboratory parameters in individuals with diabetes are potentially different from the HVRR and 2) what fold change from baseline should be expected in this population.