Quantitative Issues in Cancer Research Working Seminar

Jane Liang
Doctoral Student, Department of Biostatistics, Harvard University

“An Aggregate Utility Tool for Evaluating Genes in a Panel Test”

ABSTRACT: Panel germline testing allows for the efficient detection of multiple pathogenic variants in an individual. However, because the associations and clinical guidelines for harmful mutations and heritable diseases are not always well-established, it may not be beneficial to make panels arbitrarily large. We propose a multi-gene, multi-disease aggregate utility formula that allows the user to consider the addition or removal of each gene based on its own merits, using both quantitative measures and individualized utility costs. Our approach includes credible intervals to reflect the quality of the parameter estimates used to calculate the utility. We calculate the utilities to evaluate ATM, BRCA1, BRCA2, CHEK2, and PALB2 for possible inclusion in an opportunistic breast cancer panel. We further explore the behavior of our approach under different scenarios for a range of parameter values. Our findings suggest that rare, highly penetrant pathogenic variants tend to contribute positive net utilities, for a wide variety of userspecified utility costs and even when accounting for uncertainty in parameter estimation.