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. 2012 Jul 1;142(7):1899-1907.
doi: 10.1016/j.jspi.2012.01.024.

Adaptive Isotonic Estimation of the Minimum Effective and Peak Doses in the Presence of Covariates

Changfu Xiao  1 , Anastasia Ivanova
Affiliations

Adaptive Isotonic Estimation of the Minimum Effective and Peak Doses in the Presence of Covariates

Changfu Xiao et al. J Stat Plan Inference. .

Abstract

We consider a problem of estimating the minimum effective and peak doses in the presence of covariates. We propose a sequential strategy for subject assignment that includes an adaptive randomization component to balance the allocation to placebo and active doses with respect to covariates. We conclude that either adjusting for covariates in the model or balancing allocation with respect to covariates is required to avoid bias in the target dose estimation. We also compute optimal allocation to estimate the minimum effective and peak doses in discrete dose space using isotonic regression.

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Figures

Figure 1
Figure 1
Optimal allocation to estimate the peak dose. The solid line is the proportion assigned to the true peak dose, dτ, the dotted line proportion assigned to dK and the dashed line proportion assigned to dτ−1.
Figure 2
Figure 2
Optimal allocation to estimate the MED. The solid line is the proportion assigned to the true MED, dτ, the dotted line proportion assigned to placebo d0, the dashed line proportion assigned to dτ−1 and the dotted-dashed line to dτ+1
See this image and copyright information in PMC

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