Methods for the analysis of continuous biomarker assay data with increased sensitivity

Prospective studies must be able to adapt to improved technology and adopt new assays with increased limits of detection. Our objective is to describe methods for incorporating new technologies in which the lower limits of quantification of a biomarker are enhanced. One may conduct an analysis of data with new and old sensitivity levels using a variety of methods, including retesting a sample of stored specimens from which multiple imputation may be applied, and a parametric approach that accounts for the changing limit of detection. We compare these methods in terms of their statistical bias and efficiency and identify the conditions under which the various methods perform well and then demonstrate our methods by evaluating differences in HIV RNA levels obtained from 2 prospective cohort studies.