Present or Historical Efforts Related to Clinical Endpoint Predictivity

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Olson, et.al, Regul Toxicol Pharmacol. 2000 Aug;32(1):56-67.

Annotation: In this study, the authors analyzed a survey of 12 companies regarding 150 compounds, resulting in 221 human toxicities. They looked to determine if, when a human toxicity was observed, did the nonclinical studies predict it. They found that when they combined the results of the rondent and nonrodent species, there was a 71% concordance rate.

Human Toxicity vs. Animal Toxicity: What is a false positive and what is a false negative?
Human Toxicity?
Yes
No
Animal
Toxicity
Yes True Positive False Positive
No False Negative True Negative

PSTC initiative http://c-path.org/pstc.cfm

Annotation: Focused on biomarker development and screening.


JPMA TF1 Project

Annotation: In this project, clinical Adverse Drug Reactions (ADR's) were identified from submission documents and reviews for drugs approved in Japan between 2001 and 2010. They then determined if the nonclinical studies predicted these ADR's. The study found a 36% concordance between human ADR's and animal toxicity
Poster
Publication


Consortium for Innovation and Quality in Pharmaceutical Development (IQ Consortium)


Liver Toxicity Knowledge Base (LTKB)

Drug Discovery Today, Volume 16, Issues 15–16, August 2011, Pages 697–703
FDA LTKB Benchmark Dataset


HESI Pro-Arrhythmia

  • This group queried the FDA database for correlations between nonclinical QT changes and clinical effects. They found a moderate correlation ("at best"), with better predictivity at higher clinical exposure multiples. Findings were limited by a number of factors, including small sample size. Koerner, et.al. SOT 2012
  • It also appears that this group is collecting additional data from pharma. companies to do additional analysis on this problem.


Utilizing the Mouse Model of the Human Population to Predict DILI

Presentation


IMI eTox Initiative

eTOX Website
Int. J. Mol. Sci. 2012, 13, 3820-3846
IMI2-eTransafe to follow, starting in 2017

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Last revision by Philippe.Marc,04/12/2017