Limitations
The database collected prior to the evaluation of the models is a
retrospective database, derived from pharmacological therapeutic
monitoring data. Hospital staff may imprecisely document the time of
collection and administration. This imprecision can be up to 30 minutes.
Moreover, only population PK models developed on NONMEM® with covariates
readily available to us were evaluated. This reduces the number of
models that were assessed. This retrospective cohort study lacks
randomization, however, efforts to minimize this bias through the
addition multiple variables in the analysis were done. APEs were only
identified as of 2015 and only when treated with IV tobramycin. APEs
prior to 2015 or not treated with tobramycin were not included in the
study and may underestimate the absolute number of APE occurrences per
patient. MICs were not readily available and susceptibility was
classified as sensitive or resistant, as per our center’s microbiology
reports. This prevents the ability to capture variability inside a
susceptibility group, which is likely to underpower our ability to
identify a significant trend. Also, the smaller sample size for clinical
outcomes may further impede the likelihood of detecting trends.