Figure 6l.
In order to check, whether the selection of patients used for the
primary data set impose a bias on the resulting parameter distribution,
we fitted both models to the sparser data of additional 146 NHL patients
fulfilling weaker inclusion criteria. Table S.1.2 in Supporting
Information S.1 provides resulting individual parameters distributions.
Results are compared with the corresponding distributions of the primary
data set using Welch’s t-test (unequal sample size, unequal variances).
No significant differences were detected for the parameters of both
models indicating that bias caused by patient selection is small.
We analysed whether clinical risk factors are related to our individual
parameter estimates derived from fitting all cycles (Supporting
information S.5). Several significant associations were found. The
pharmacodynamics effect of cyclophosphamide showed the strongest
dependence on clinical factors. Most of these dependences are
consistently observed for both data sets.
We finally determined sensitivity as well as the Youden index of both
models to predict severe grade 3-4 thrombopoenia at the next cycle. The
mechanistic model showed superior sensitivity (Figure 7) prediction
performance throughout (Figure 8).