Online Supplement Forpage 1 of 10

Online Supplement forPage 1 of 10

Development of a New Pre- and Post-processing Tool
(SADAPT-TRAN) for Nonlinear Mixed-effects Modeling in S-ADAPT

Legends toFigures

Figure S1:Differential equation subroutine (DIFFEQ) in Fortran format specifying the differential equations and calculation of variables that change continuously over time

Figure S2:OUTPUT subroutine in Fortran format defining parameter transformations, assigning global variable names, initial conditions, and output equations

Figure S3:VARMOD subroutine in Fortran format defining the residual error variance for every dependent variable

Figure S4:SYMBOL subroutine in Fortran format assigning parameter symbols

Figure S5:POPTRN (left) and POPITRN (right) subroutines in Fortran format defining the forward and inverse parameter transformations

Figure S6:POPFINAL subroutine in Fortran format containing the code to print the present parameter estimates (part A), code to specify the variance burn phase for clearance (CL), code for the variance burn then shrink phase for the Hill coefficient, and code to define the structure of the variance covariance matrix (part B). Code for the model parameters other than CL and HILL not shown.

Figure S7:Section of the OUTPUT and of the POPFINAL subroutine defining between occasion variability (BOV) for clearance at two occasions. Please note that BOV is not part of the model shown in this manuscript. This code is only provided as an example for specifying BOV.

Figure S1:Differential equation subroutine (DIFFEQ) in Fortran format specifying the differential equations and calculation of variables that change continuously over time

Figure S2:OUTPUT subroutine in Fortran format defining parameter transformations, assigning global variable names, initial conditions, and output equations

Figure S3:VARMOD subroutine in Fortran format defining the residual error variance for every dependent variable

Figure S4:SYMBOL subroutine in Fortran format assigning parameter symbols

Figure S5:POPTRN (left) and POPITRN (right) subroutines in Fortran format defining the forward and inverse parameter transformations

Figure S6:POPFINAL subroutine in Fortran format containing the code to print the present parameter estimates (part A), code to specify the variance burn phase for clearance (CL), code for the variance burn then shrink phase for the Hill coefficient, and code to define the structure of the variance covariance matrix (part B). Code for the model parameters other than CL and HILL not shown.

Part A

Figure S6:Part B

Figure S7:Section of the OUTPUT and of the POPFINAL subroutine defining between occasion variability (BOV) for clearance at two occasions. Please note that BOV is not part of the model shown in this manuscript. This code is only provided as an example for specifying BOV.