## Abstract

Constructing a confidence interval for the ratio of bivariate normal means is a classical problem in statistics. Several methods have been proposed in the literature. The Fieller method is known as an exact method, but can produce an unbounded confidence interval if the denominator of the ratio is not significantly deviated from 0; while the delta and some numeric methods are all bounded, they are only first-order correct. Motivated by a real-world problem, we propose the penalized Fieller method, which employs the same principle as the Fieller method, but adopts a penalized likelihood approach to estimate the denominator. The proposed method has a simple closed form, and can always produce a bounded confidence interval by selecting a suitable penalty parameter. Moreover, the new method is shown to be second-order correct under the bivariate normality assumption, that is, its coverage probability will converge to the nominal level faster than other bounded methods. Simulation results show that our proposed method generally outperforms the existing methods in terms of controlling the coverage probability and the confidence width and is particularly useful when the denominator does not have adequate power to reject being 0. Finally, we apply the proposed approach to the interval estimation of the median response dose in pharmacology studies to show its practical usefulness.

Original language | English (US) |
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Journal | Biometrics |

DOIs | |

State | Accepted/In press - 2020 |

### Bibliographical note

Funding Information:The authors would like to thank the associate editor, the two anonymous reviewers, and the co‐editor for their constructive comments which greatly improved the presentation of this article. The authors also appreciate the help of Raymond J. Carroll, PhD for his critical reading of the original version of the manuscript. This work is partially supported by National Institutes of Health grants R03‐DE024198 and R03‐DE025646.

## Keywords

- confidence interval
- coverage probability
- penalized Fieller method
- ratio of means
- second-order correct