. 2021 Oct 26;11(1):7–19. doi: 10.1002/psp4.12728

TABLE 2.

Parameter estimates for the final population PK‐PD model

	Parameter (unit)	NONMEM		Bootstrap
	Parameter (unit)	Estimate	95% CI	Median	95% CI ^a
Fixed effect	BL	1.40	1.39, 1.41	1.40	1.39, 1.41
	K _out (1/h)	8.51 E−05	7.59E−5, 9.42E−5	8.40E−05	7.55E−5, 9.35E−5
	E_max	0.702	0.606, 0.797	0.697	0.616, 0.820
	EC₅₀ (mg/L)	46.4	33.8, 59.0	45.2	35.2, 61.0
Covariate effect
Effect of weight	WT on K _out	0.414	0.155, 0.673	0.403	0.132, 0.645
Effect of age	BL	0.101	0.0326, 0.169	0.0954	0.0282, 0.177
Effect of ApoE ε4	Noncarrier on BL	−0.0404	−0.0547, −0.0260	−0.0402	−0.0571, −0.0246
	Carrier (2 copies) on BL	0.00896	−0.0096, 0.0275	0.00923	−0.00987, −0.0270
Effect of MMSEBL	MMSEBL on BL	−0.186	−0.256, −0.116	−0.187	−0.263, −0.116
IIV ^b	K _out, % CV	44.2	29.8, 54.9	43.1	31.3, 55.8
	E_max, % CV	25.3	15.8, 32.0	24.0	13.1, 32.6
	BL, % CV	12.8	12.2, 13.3	12.8	12.1, 13.5
	EC₅₀, % CV	84.1	72.6, 94.2	84.9	69.9, 100
	ρ (K _out, E_max)	−0.872	−3.17, −0.245	−0.863	−3.71, −0.232
	ρ (E_max, BL)	0.439	0.157, 0.593	0.378	0.107, 0.601
	ρ (BL, EC₅₀)	−0.406	−0.772, −0.151	−0.457	−0.854, −0.143
Residual error	Proportional error (%)	4.04	3.89, 4.18	4.03	3.86, 4.20

ApoE, apolipoprotein E; BL, baseline SUVR; CV, coefficient of variation; EC₅₀, aducanumab exposure that produces 50% of the maximum attainable stimulation; E_max, maximum fold change in the elimination of SUVR as a response to aducanumab exposure; K _in, zero‐order rate for production of SUVR; K _out, first‐order rate of elimination of SUVR; MMSEBL, Mini‐Mental State Examination score at baseline; NONMEM, nonlinear mixed‐effect modeling software; ρ, correlation; PD, pharmacodynamic; PK, pharmacokinetic; WT, weight.

^{^a}

One hundred twenty‐two runs were skipped while calculating bootstrap summaries.

^{^b}

%CV = $100 * (\sqrt{\exp^{ω 2} ‐ 1})$ .