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Keywords:

  • Constrained MLE;
  • Exact test;
  • Two-by-two table;
  • Unconditional distribution

Summary. Confidence intervals are often provided to estimate a treatment difference. When the sample size is small, as is typical in early phases of clinical trials, confidence intervals based on large sample approximations may not be reliable. In this report, we propose test-based methods of constructing exact confidence intervals for the difference in two binomial proportions. These exact confidence intervals are obtained from the unconditional distribution of two binomial responses, and they guarantee the level of coverage. We compare the performance of these confidence intervals to ones based on the observed difference alone. We show that a large improvement can be achieved by using the standardized Z test with a constrained maximum likelihood estimate of the variance.