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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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MTD. Specifically, after k patients have been observed, the dose for the next patient accrued to the trial is x k þ 1 ¼ F ± 1 k ð a Þ ð 11 Þ where F k ð x Þ ¼ Z x 0 Z X Y k ð g ; N Þ d N d g ð 12 Þ is the marginal posterior CDF of the MTD given D k . Thus, subsequent to the first cohort of patients, the dose selected for each patient corresponds to the dose having minimal posterior expected loss with respect to L ð x ; N Þ ¼ a ð g ± x Þ if x V g ð i : e :; if x is an underdose Þ ð 1 ± a Þð x ± g Þ if x > c ð i : e :; if x is an overdose Þ : 8 < : The use of this loss function implies that for any y > 0 the loss incurred by treating a patient at y units above the MTD is (1 ± a )/ a times greater than the loss associated with treating the patient at y units below the MTD. This interpretation might provide a meaningful basis for the selection of the feasibility bound (Babb et al., 1998). The value selected for the feasibility bound will determine the rate of change in dose level between successive patients. Low values will result in a cautious escalation scheme with relatively small increments in dose, while high values would result in a
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