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Non-inferiority tests for clustered matched-pair data
1Biostatistics Branch, DCEG, National Cancer Institute, National Institutes of Health, DHHS, Rockville, MD 20852-7244, U.S.A. namj@mail.nih.gov
Statistics in Medicine
|March 28, 2009
Summary
For clustered matched-pair studies, standard non-inferiority tests may fail. Adjusted score tests and modified Obuchowski
Area of Science:
- Biostatistics
- Clinical Trials
Background:
- Non-inferiority tests for matched-pair data assume pair independence, which is violated in clustered designs.
- Clustered data introduces intra-cluster correlation, necessitating adjustments to standard statistical tests.
Purpose of the Study:
- To evaluate the performance of adjusted non-inferiority tests for clustered matched-pair data.
- To compare adjusted score, Wald-type, and modified Obuchowski's methods against a moments estimate test.
- To assess Type 1 error rates and statistical power under various correlation structures and small cluster sizes.
Main Methods:
- Simulations were conducted to compare statistical tests under different correlation structures.
- Evaluated Type 1 error rates and power for adjusted score, Wald-type, and modified Obuchowski's methods.
- Compared these methods against a non-inferiority test based on a method of moments estimate.
Main Results:
- Adjusted score tests and modified Obuchowski's method showed accurate Type 1 error rates, similar to the moments estimate test.
- The moments estimate test exhibited inaccurate Type 1 error rates with small cluster numbers (≤25) and low response rates (≤20%).
- Adjusted score, moments estimate, and modified tests demonstrated comparable statistical power, while the adjusted Wald-type test was overly anti-conservative.
Conclusions:
- Adjusted score tests and modified Obuchowski's method are reliable for non-inferiority testing in clustered matched-pair studies.
- The number of clusters significantly impacts the accuracy of Type 1 error rates and power.
- Sufficiently large cluster numbers are crucial for robust non-inferiority study design in clustered matched-pair settings.
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