Sample size calculation for phylogenetic case linkage

Area of Science:

• Epidemiology
• Genomics
• Biostatistics

Background:

• Sample size calculations are vital for scientific study design and evaluation.
• Phylogenetic studies are increasingly important for understanding pathogen transmission.
• Clear guidance for sample size determination in phylogenetic studies is lacking.

Purpose of the Study:

• To introduce a statistical framework for determining sample size in phylogenetic studies.
• To assess how study design and linkage criteria influence the identification of true infector-infectee transmission pairs.
• To provide a tool for designing and evaluating pathogen phylogenetic studies.

Main Methods:

• Developed a statistical framework to calculate the number of true infector-infectee pairs based on study size and population coverage.
• Investigated the impact of linkage criteria and study design on identifying transmission links.
• Utilized outbreak simulations to test the framework and provide guidance on calculating sensitivity and specificity of linkage criteria.

Main Results:

• The study presents a method to determine the number of true transmission pairs identifiable by phylogenetic studies.
• Demonstrated how study design elements can counterintuitively affect the accuracy of identifying transmission links.
• Offered guidance for calculating sensitivity and specificity of linkage criteria, essential inputs for the framework.

Conclusions:

• The developed statistical framework aids in determining appropriate sample sizes for phylogenetic studies of pathogen transmission.
• The R package 'phylosamp' is available for practical application in study design and evaluation.
• This approach is broadly applicable to various pathogen phylogenetic studies, enhancing their rigor and accuracy.