Stratified exact tests for the weak causal null hypothesis in randomized trials with a binary outcome.

Fisher's exact test is commonly used to compare two groups when the outcome is binary in randomized trials. In the context of causal inference, this test explores the sharp causal null hypothesis (i.e. the causal effect of treatment is the same for all subjects), but not the weak causal null hypothesis (i.e. the causal risks are the same in the two groups). Therefore, in general, rejection of the null hypothesis by Fisher's exact test does not mean that the causal risk difference is not zero. Recently, Chiba (Journal of Biometrics and Biostatistics 2015; 6: 244) developed a new exact test for the weak causal null hypothesis when the outcome is binary in randomized trials; the new test is not based on any large sample theory and does not require any assumption. In this paper, we extend the new test; we create a version of the test applicable to a stratified analysis. The stratified exact test that we propose is general in nature and can be used in several approaches toward the estimation of treatment effects after adjusting for stratification factors. The stratified Fisher's exact test of Jung (Biometrical Journal 2014; 56: 129-140) tests the sharp causal null hypothesis. This test applies a crude estimator of the treatment effect and can be regarded as a special case of our proposed exact test. Our proposed stratified exact test can be straightforwardly extended to analysis of noninferiority trials and to construct the associated confidence interval.