Title

Two-stage k-sample designs for the ordered alternative problem

Document Type

Article

Publication Date

7-2012

Publication Title

Pharmaceutical Statistics

Volume

11

Issue

4

First page number:

287

Last page number:

294

Abstract

In preclinical studies and clinical dose-ranging trials, the Jonckheere-Terpstra test is widely used in the assessment of dose-response relationships. Hewett and Spurrier (1979) presented a two-stage analog of the test in the context of large sample sizes. In this paper, we propose an exact test based on Simon's minimax and optimal design criteria originally used in one-arm phase II designs based on binary endpoints. The convergence rate of the joint distribution of the first and second stage test statistics to the limiting distribution is studied, and design parameters are provided for a variety of assumed alternatives. The behavior of the test is also examined in the presence of ties, and the proposed designs are illustrated through application in the planning of a hypercholesterolemia clinical trial. The minimax and optimal two-stage procedures are shown to be preferable as compared with the one-stage procedure because of the associated reduction in expected sample size for given error constraints.

Keywords

Anticholesteremic agents; Anticholesteremic Agents/administration & dosage; Anticholesteremic Agents/therapeutic use; Clinical trials; Clinical trials—Methodology; Clinical Trials; Phase II as Topic/methods; Data Interpretation; Statistical; Design—Research; Designs; Dose-Response Relationship; Drug; Drugs--Dose-response relationship; Endpoint Determination; Exact tests; Humans; Hypercholesteremia; Hypercholesterolemia/drug therapy; Jonckheere–Terpstra test; Nonparametric; Nonparametric statistics; Pharmaceutical Preparations/administration & dosage; Research Design; Translating and interpreting--Data processing

Disciplines

Clinical Trials | Medicine and Health Sciences | Statistical Methodology | Statistics and Probability | Vital and Health Statistics

Language

English

Permissions

Use Find in Your Library, contact the author, or interlibrary loan to garner a copy of the item. Publisher policy does not allow archiving the final published version. If a post-print (author's peer-reviewed manuscript) is allowed and available, or publisher policy changes, the item will be deposited.

Identifier

DOI: 10.1002/pst.1499

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