Table 5.

Power of the NPDE-based model evaluation approach (negative-control simulation study)

Number of Subjects	Samples per Subject	Total Samples	Iterationsa	P-value (μNPDE)b	P-value (NPC)c
5	3	15	446	0.43	0.735
10	3	30	485	0.79	0.973
20	3	60	492	0.98	1
30	3	90	495	1	1
5	6	30	487	0.511	0.891
10	6	60	498	0.869	0.998
20	6	120	500	0.996	1
30	6	180	499	1	1
5	9	45	497	0.503	0.942
10	9	90	499	0.866	0.998
20	9	180	499	0.984	1
30	9	270	499	1	1

μ_NPDE, mean of normalized prediction distribution errors; NPC, numerical predictive check

^aIterations (out of 500) where the standard deviation of NPDE were not optimized to within ±0.01 of the target value (i.e., 1) by the developed fitting algorithm were excluded from the analysis.

^bPower of the NPDE-based model evaluation approach. Computed as the proportion of iterations where the μ_NPDE was statistically different than 0 (p-value<0.05; two-sided Student’s t-test).

^cPower of the conventional evaluation approach. Computed as the proportion of iterations where the proportion of observed data exceeding the model’s 90% prediction interval was statistically > 0.10 (p-value < 0.05; exact binomial test)