A modified maximum contrast method for unequal sample sizes in pharmacogenomic studies

TL;DR

This paper introduces a modified maximum contrast method for pharmacogenomic studies that improves detection power and reduces false positives, especially with unequal sample sizes, by eliminating dependence on nuisance parameters.

Contribution

The paper proposes a new modified maximum contrast method that is faster, more accurate, and less dependent on nuisance parameters compared to existing approaches.

Findings

The modified maximum contrast method has the lowest false-positive rate.

It is faster and more accurate than the permuted version.

Simulation studies confirm its effectiveness in various conditions.

Abstract

In pharmacogenomic studies, biomedical researchers commonly analyze the association between genotype and biological response by using the Kruskal--Wallis test or one-way analysis of variance (ANOVA) after logarithmic transformation of the obtained data. However, because these methods detect unexpected biological response patterns, the power for detecting the expected pattern is reduced. Previously, we proposed a combination of the maximum contrast method and the permuted modified maximum contrast method for unequal sample sizes in pharmacogenomic studies. However, we noted that the distribution of the permuted modified maximum contrast statistic depends on a nuisance parameter $\sigma^2$, which is the population variance. In this paper, we propose a modified maximum contrast method with a statistic that does not depend on the nuisance parameter. Furthermore, we compare the performance of these methods via simulation studies. The simulation results showed that the modified maximum contrast method gave the lowest false-positive rate; therefore, this method is powerful for detecting the true response patterns in some conditions. Further, it is faster and more accurate than the permuted modified maximum contrast method. On the basis of these results, we suggest a rule of thumb to select the appropriate method in a given situation.