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[生物书合集].Advances.in.Clinical.TBiostatisti

[生物书合集].Advances.in.Clinical.TBiostatisti

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5-FU suggested that, when given in combination with topotecan, the MTD of 5-FU was a priori believed to be less than 425 mg/m 2 . In consequence, the support of the prior for the MTD was finite. In many contexts, there will not be sufficient information available prior to the onset of the phase I trial to unambiguously determine a suitable upper bound for the MTD (and hence for the range of dose levels to be searched). In this case, one might introduce a hyperparameter X max and specify a joint prior distribution for the MTD and X max as h ð g ; X max Þ ¼ f 1 ð g j X max Þ f 0 ð X max Þ with, to continue the 5-FU example, f 1 ( g j X max ) denoting the probability density function (pdf) of a uniform random variable on [140, 425] and f 0 ( X max ) a monotone decreasing pdf defined on [425, l ), such as a truncated normal with mean 425 and suitable standard deviation. Flournoy (1993) considered the two-parameter logistic model in Eq. (3) reparameterized in terms of the MTD and the nuisance parameter N = h 2 . The parameters g and N
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