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For plasma PK profiles and urinary metabolite ratios, model qualification was performed by comparing population mean or individual values of the observations with the model predictions.
Model qualification was performed by comparing clinically measured SLD with those predicted by the model, evaluating the uncertainty in parameter values, and using the model to perform a simulation of two sets of 10,000 virtual patients.
Model qualification was conducted using standard nonparametric bootstrap (n = 1,000) and visual predictive check to evaluate the precision of model parameter estimates and robustness of the final PK and efficacy models.
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A schematic overview of the model qualification is provided in Figure 5.
The level of model qualification is dependent on the question being addressed.
The objective of model qualification is to examine whether the model is suitable for the proposed applications.
In addition, regulatory acceptance of systems pharmacology model qualification is needed to ensure that integrated knowledge can assist in model-informed trial design and in extrapolations beyond the observed data range.
Also acknowledged was that system model qualification is an area that has not been extensively discussed within the PBPK community and that standards are not currently agreed, and that progress to establish best practice is needed.
Little qualification was found here.
Education qualification was classified as no secondary qualification attained (reference) and attained secondary qualification or higher.
An important issue in this regard is that model qualification by regulators is not only model validation per se but an evaluation of the modeling and simulation approach as an integral part of drug development.
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