Equal-tailed confidence intervals for comparison of rates

Several methods are available for generating confidence intervals for rate difference, rate ratio, or odds ratio, when comparing two independent binomial proportions or Poisson (exposure-adjusted) incidence rates. Most methods have some degree of systematic bias in one-sided coverage, so that a nominal 95% two-sided interval cannot be assumed to have tail probabilities of 2.5% at each end, and any associated hypothesis test is at risk of inflated typeI error rate. Skewness-corrected asymptotic score methods have been shown to have superior equal-tailed coverage properties for the binomial case. This paper completes this class of methods by introducing novel skewness corrections for the Poisson case and for odds ratio, with and without stratification. Graphical methods are used to compare the performance of these intervals against selected alternatives. The skewness-corrected methods perform favourably in all situationsincluding those with small sample sizes or rare eventsand the skewness correction should be considered essential for analysis of rate ratios. The stratified method is found to have excellent coverage properties for a fixed effects analysis. In addition, another new stratified score method is proposed, based on the t-distribution, which is suitable for use in either a fixed effects or random effects analysis. By using a novel weighting scheme, this approach improves on conventional and modern meta-analysis methods with weights that rely on crude estimation of stratum variances. In summary, this paper describes methods that are found to be robust for a wide range of applications in the analysis of rates.