Statistical Methods for Evaluating Novel CD4 Enumeration Technologies.

摘要

Method comparison studies are often conducted in medical research to determine whether a novel method of clinical measurement can replace or be used interchangeably with the reference standard method. An increasing number of method comparison studies have recently appeared in the HIV literature, as novel technologies have been developed to measure a critical biomarker for HIV care, the CD4 count. Though most of these studies have been cross-sectional in design, the primary question of interest is longitudinal in nature, namely, how would timing of clinical decision-making change if CD4 monitoring were based on the novel technology rather than the reference standard. To explore how both properties of the CD4 enumeration technology used and the protocol for monitoring (including choice of threshold, frequency of measurement, and requirement of a confirmatory measurement) might impact timing of treatment initiation, we use a combination of statistical modeling and simulation study. We then use the results to inform the design of cross-sectional method comparison studies and describe some fundamental issues for investigators undertaking these studies, including sample size considerations, sampling schemes, and methods of data analysis.