| Abstract: | Tests for a monotonic trend between an ordered categorical exposure and disease status are routinely carried out from case‐control data using the Mantel‐extension trend test or the asymptotically equivalent Cochran‐Armitage test. In this study, we considered two alternative tests based on isotonic regression, namely an order‐restricted likelihood ratio test and an isotonic modification of the Mantel‐extension test extending the recent proposal by Mancuso, Ahn and Chen (2001) to case‐control data. Furthermore, we considered three tests based on contrasts, namely a single contrast (SC) test based on Schaafsma's coefficients, the Dosemeci and Benichou (DB) test, a multiple contrast (MC) test based on the Helmert, reverse‐Helmert and linear contrasts and we derived their case‐control versions. Using simulations, we compared the statistical properties of these five alternative tests to those of the Mantel‐extension test under various patterns including no relationship, as well as monotonic and non‐monotonic relationships between exposure and disease status. In the case of no relationship, all tests had close to nominal type I error except in situations combining a very unbalanced exposure distribution and small sample size, where the asymptotic versions of the three tests based on contrasts were highly anticonservative. The use of bootstrap instead of asymptotic versions corrected this anticonservatism. For monotonic patterns, all tests had close powers. For non monotonic patterns, the DB‐test showed the most favourable results as it was the least powerful test. The two tests based on isotonic regression were the most powerful tests and the Mantel‐extension test, the SC‐ and MC‐tests had in‐between powers. The six tests were applied to data from a case‐control study investigating the relationship between alcohol consumption and risk of laryngeal cancer in Turkey. In situations with no evidence of a monotonic relationship between exposure and disease status, the three tests based on contrasts did not conclude in favour of a significant trend whereas all the other tests did. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim) |
