The Variance-Stabilizing Transformation for the Poisson Rate Ratio: Closed-Form Confidence Intervals

Read the full article See related articles

Discuss this preprint

Start a discussion What are Sciety discussions?

Listed in

This article is not in any list yet, why not save it to one of your lists.
Log in to save this article

Abstract

The incidence rate ratio R is the standard measure for comparing event rates in clinical trials and epidemiology. In vaccine trials, the vaccine efficacy is VE = 1− R . When events are rare, the two arm counts are Poisson. The estimator of R is heteroskedastic: its sampling variance changes with the data. So no fixed-width interval covers correctly everywhere. The usual log-Wald interval is undefined at zero events and covers poorly at small counts. Early vaccine and drug-safety readouts fall in exactly this regime. We show that a single reparameterization collapses this bivariate problem to an effective one-parameter family with a quadratic variance function, whose variance-stabilizing transformation is 2 arcsinh . The reduction yields a closed-form confidence interval for R . Its two leading errors, a curvature bias and the variability of the estimated scale, each admit a closed-form correction with no tuning constants. In a Monte Carlo study of our seven arcsinh variants and five competitors, the +Curve+Stu variant covers within 0.002 of the nominal 0.95 for about 50 control and 5 treatment events. Its width is on par with the best competitor. It avoids the conservatism and zero-count breakdown of log-Wald and MOVER. For moderate counts, we recommend this interval; for sparser data, our Bar-Lev–Enis count-shift variant is more robust. The result is a ready-to-use, closed-form interval for the low-count regime. We illustrate it on early Covid-19 vaccine-efficacy readouts and provide reference implementations in R and Python.

Article activity feed