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Point and Interval Estimators of the Target Dose in Clinical Dose-Finding Studies with Active Control.

Helms HJ, Benda N, Friede T - J Biopharm Stat (2014)

Bottom Line: The main focus of such studies often lies on the estimation of a target dose that leads to the same efficacy as the control.This article investigates the finite sample properties of the maximum likelihood estimation of the target dose and compares several approaches for constructing corresponding confidence intervals under the assumption of a linear dose-response curve and normal error terms.Furthermore, the impact of deviations from the model assumptions regarding the error distribution is explored.

View Article: PubMed Central - PubMed

Affiliation: a Department of Medical Statistics , University Medical Center Göttingen , Humboldtallee , Göttingen , Germany.

ABSTRACT
In a clinical dose finding study with active control a new drug with several dose levels is compared with an active comparator drug. The main focus of such studies often lies on the estimation of a target dose that leads to the same efficacy as the control. This article investigates the finite sample properties of the maximum likelihood estimation of the target dose and compares several approaches for constructing corresponding confidence intervals under the assumption of a linear dose-response curve and normal error terms. Furthermore, the impact of deviations from the model assumptions regarding the error distribution is explored.

No MeSH data available.


Related in: MedlinePlus

Median interval length of the ∆-method, the method by Fisch and Strehlau (F&S), the parametric bootstrap, and the profile likelihood for various variances σ2, slopes θ1, and group sample sizes n.
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Related In: Results  -  Collection


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Figure 0004: Median interval length of the ∆-method, the method by Fisch and Strehlau (F&S), the parametric bootstrap, and the profile likelihood for various variances σ2, slopes θ1, and group sample sizes n.

Mentions: Now the median length of the different intervals will be investigated. Because a closed expression of the confidence interval only exists for the ∆-method (see Section 2.3.1) the length will be investigated via simulation. Therefore, the scenarios defined in Table 1 will be simulated under the same conditions as described in Section 3. In Fig. 4 it can be seen that the confidence interval length is relatively similar for all four methods. But in all scenarios the median length of the ∆-method is a little bit smaller than the length for the other three methods. This is possible even if the ∆-method is more conservative than the other three methods because the ∆-method generate symmetric confidence intervals and all other methods generates asymmetric confidence intervals. This will be explained in more detail in a simulated example next.


Point and Interval Estimators of the Target Dose in Clinical Dose-Finding Studies with Active Control.

Helms HJ, Benda N, Friede T - J Biopharm Stat (2014)

Median interval length of the ∆-method, the method by Fisch and Strehlau (F&S), the parametric bootstrap, and the profile likelihood for various variances σ2, slopes θ1, and group sample sizes n.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4566885&req=5

Figure 0004: Median interval length of the ∆-method, the method by Fisch and Strehlau (F&S), the parametric bootstrap, and the profile likelihood for various variances σ2, slopes θ1, and group sample sizes n.
Mentions: Now the median length of the different intervals will be investigated. Because a closed expression of the confidence interval only exists for the ∆-method (see Section 2.3.1) the length will be investigated via simulation. Therefore, the scenarios defined in Table 1 will be simulated under the same conditions as described in Section 3. In Fig. 4 it can be seen that the confidence interval length is relatively similar for all four methods. But in all scenarios the median length of the ∆-method is a little bit smaller than the length for the other three methods. This is possible even if the ∆-method is more conservative than the other three methods because the ∆-method generate symmetric confidence intervals and all other methods generates asymmetric confidence intervals. This will be explained in more detail in a simulated example next.

Bottom Line: The main focus of such studies often lies on the estimation of a target dose that leads to the same efficacy as the control.This article investigates the finite sample properties of the maximum likelihood estimation of the target dose and compares several approaches for constructing corresponding confidence intervals under the assumption of a linear dose-response curve and normal error terms.Furthermore, the impact of deviations from the model assumptions regarding the error distribution is explored.

View Article: PubMed Central - PubMed

Affiliation: a Department of Medical Statistics , University Medical Center Göttingen , Humboldtallee , Göttingen , Germany.

ABSTRACT
In a clinical dose finding study with active control a new drug with several dose levels is compared with an active comparator drug. The main focus of such studies often lies on the estimation of a target dose that leads to the same efficacy as the control. This article investigates the finite sample properties of the maximum likelihood estimation of the target dose and compares several approaches for constructing corresponding confidence intervals under the assumption of a linear dose-response curve and normal error terms. Furthermore, the impact of deviations from the model assumptions regarding the error distribution is explored.

No MeSH data available.


Related in: MedlinePlus