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Step-down trend tests for identifying the minimum effective dose

D Amaratunga1, N Ge

  • 1Department of Preclinical Biostatistics, R.W. Johnson Pharmaceutical Research Institute, Raritan, New Jersey 08869-0602, USA.

Journal of Biopharmaceutical Statistics
|April 21, 1998
PubMed
Summary
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A new method, SD2B, consistently outperforms the SD2L procedure for determining the minimum effective dose in dose-response studies. Replacing linear contrast tests with Bartholomew's test significantly improves efficiency, especially in complex scenarios.

Area of Science:

  • Biostatistics
  • Pharmacometrics
  • Statistical Methods

Background:

  • Determining the minimum effective dose (MED) is crucial in dose-response studies.
  • The SD2L procedure, recommended by Tamhane et al., demonstrated good performance in balanced, normal, homoscedastic conditions.
  • Existing methods require evaluation under diverse conditions to ensure robust performance.

Purpose of the Study:

  • To introduce and evaluate a novel step-down procedure (SD2B) for MED determination.
  • To compare the performance of SD2B against the established SD2L procedure.
  • To assess the efficacy of SD2B and a related method (SD2W) under various statistical conditions.

Main Methods:

  • Developed the SD2B procedure by replacing the linear contrast trend test in SD2L with Bartholomew's test.

Related Experiment Videos

  • Conducted simulation studies to evaluate finite sample performance.
  • Examined procedures under balanced, unbalanced, homoscedastic, and heteroscedastic conditions.

    • Main Results:

    • The SD2B procedure consistently outperformed the SD2L method in efficiency.
    • The SD2W procedure, utilizing Welch's test, showed further improvement in heteroscedastic situations.
    • Efficiency gains of SD2B and SD2W over SD2L frequently exceeded 10%.

    Conclusions:

    • The SD2B procedure offers a more efficient approach to determining the minimum effective dose compared to SD2L.
    • Bartholomew's test integration enhances the robustness of dose-response analysis.
    • The findings support the use of SD2B and SD2W in dose-response studies, particularly under non-ideal conditions.