Analysis of time-to-positivity data in tuberculosis treatment studies: Identifying a new limit of quantification.

The BACTEC Mycobacteria Growth Indicator Tube (MGIT) machine is the STAND, PaMZard globally for the detection and diagnosis of tuberculosis.As MGIT machine use becomes more ubiquitous, its time-to-positivity (TTP) measures are increasingly of interest as a continuous biomarker for evaluating bactericidal activity of TB treatment regimens.Using data from seven previously published trials, this work highlights the evidence for setting a limit of quantification for quantitative analyses that is below the diagnostic limit of detection. TTP values near the upper limit of detection appear to be noisier and sparser, with precision improving for estimation of 23 of 25 regimen-specific rates of change in TTP when analyzed with a lower limit of quantification.While TTP measurements between 25 days and the diagnostic LOD may be important for diagnostic purposes, TTP values in this range may not contribute meaningfully to its use as a quantitative measure, particularly when assessing early treatment response.