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Updated: Aug 5, 2025
Quantification and Whole Genome Characterization of SARS-CoV-2 RNA in Wastewater and Air Samples
Published on: June 30, 2023
Statistical Challenges when Analyzing SARS-CoV-2 RNA Measurements Below the Assay Limit of Quantification in COVID-19
Carlee B Moser1, Kara W Chew2, Mark J Giganti1
1Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, 02115, USA.
Abstract:
Most clinical trials evaluating COVID-19 therapeutics include assessments of antiviral activity. In recently completed outpatient trials, changes in nasal SARS-CoV-2 RNA levels from baseline were commonly assessed using analysis of covariance (ANCOVA) or mixed models for repeated measures (MMRM) with single-imputation for results below assay lower limits of quantification (LLoQ). Analyzing changes in viral RNA levels with singly-imputed values can lead to biased estimates of treatment effects. In this paper, using an illustrative example from the ACTIV-2 trial, we highlight potential pitfalls of imputation when using ANCOVA or MMRM methods, and illustrate how these methods can be used when considering values
