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Stochastic Ordering under Conditional Modelling of Extreme Values: Drug-Induced Liver Injury
Drug-induced liver injury (DILI) is a major public health issue and of
serious concern for the pharmaceutical industry. Early detection of signs of a
drug's potential for DILI is vital for pharmaceutical companies' evaluation of
new drugs. A combination of extreme values of liver specific variables indicate
potential DILI (Hy's Law). We estimate the probability of severe DILI using the
Heffernan and Tawn (2004) conditional dependence model which arises naturally
in applications where a multidimensional random variable is extreme in at least
one component. We extend the current model by including the assumption of
stochastically ordered survival curves for different doses in a Phase 3 study.Comment: 24 pages, 5 figure
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