Statistical Challenges when Analyzing SARS-CoV-2 RNA Measurements Below the Assay Limit of Quantification in COVID-19 Clinical Trials.

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

SUBMITTER: Moser CB 

PROVIDER: S-EPMC10055451 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature