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Tests for overall trend, such as the Mantel extension test, are not tests for monotonic dose response. A survey of epidemiologic articles shows widespread misinterpretation of the Mantel extension test and overstatement of evidence for monotonic dose response when there are few exposed subjects. To properly evaluate the hypothesis that risk continues to increase with further increases in exposure, one must examine several statistics and estimates. Given sufficient data, nonparametric or polynomial regression analyses can provide more detailed dose-response information.
Madure et al. (Wed,) studied this question.