Date of Award:

5-2019

Document Type:

Dissertation

Degree Name:

Doctor of Philosophy (PhD)

Department:

Mathematics and Statistics

Committee Chair(s)

Chris Corcoran

Committee

Chris Corcoran

Committee

Adele Cutler

Committee

John Stevens

Committee

David Brown

Committee

Tyler Brough

Abstract

The vast and complex wealth of information available to researchers often leads to a systematic review, which involves a detailed and comprehensive plan and search strategy with the goal of identifying, appraising, and synthesizing all relevant studies on a particular topic. A meta–analysis, conducted ideally as part of a comprehensive systematic review, statistically synthesizes evidence from multiple independent studies to produce one overall conclusion. The increasingly widespread use of meta–analysis has led to growing interest in meta–analytic methods for rare events and sparse data. Conventional approaches tend to perform very poorly in such settings. Recent work in this area has provided options for sparse data, but these are still often hampered when heterogeneity across the available studies differs based on treatment group. Heterogeneity arises when participants in a study are more correlated than participants across studies, often stemming from differences in the administration of the treatment, study design, or measurement of the outcome. We propose several new exact methods that accommodate this common contingency, providing more reliable statistical tests when such patterns on heterogeneity are observed. First, we develop a permutation–based approach that can also be used as a basis for computing exact confidence intervals when estimating the effect size. Second, we extend the permutation–based approach to the network meta–analysis setting. Third, we develop a new exact confidence distribution approach for effect size estimation. We show these new methods perform markedly better than traditional methods when events are rare, and heterogeneity is present.

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