How Often Do Safety Signals Occur by Chance in First-in-Human Trials?

Gemma L Clayton, Asher D Schachter, Baldur Magnusson, Yue Li, Laurence Colin

Research output: Contribution to journalArticle (Academic Journal)

1 Citation (Scopus)
205 Downloads (Pure)

Abstract

Clinicians working on first-in-human clinical studies need to be able to judge whether safety signals observed on an investigational drug were more likely to have occurred by chance or to have been caused by the drug. We retrospectively reviewed 84 Novartis studies including 1,234 healthy volunteers receiving placebo to determine the expected incidence of changes in commonly measured laboratory parameters and vital signs, in the absence of any active agent. We calculated the frequency of random incidence of safety signals, focusing on the liver, cardiovascular system, kidney, and pancreas. Using the liver enzyme alanine aminotransferase (ALT) as an example, we illustrate how a predictive model can be used to determine the probability of a given subject to experience an elevation of ALT above the upper limit of the normal range under placebo, conditional on the characteristics of this subject and the study.

Original languageEnglish
Pages (from-to)471-476
Number of pages6
JournalClinical and Translational Science
Volume11
Issue number5
Early online date27 Apr 2018
DOIs
Publication statusPublished - 1 Sep 2018

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