[Psn-general] Help getting MCMP to work in PsN

[<R.t...@ra...>]

Dear all,

I’m trying to get some hands-on experience with the MCMP method that has been implemented in PSN. For this purpose I have generated a “full” and “reduced” simulation control stream, as well as a dataset with 40 individuals all getting the same dose of a drug that is cleared renally. My purpose is to determine the number of individuals needed to identify renal function as a covariate for clearance.

However, when I run the command "/usr/bin/mcmp -full_model=MCMPfull.ctl -reduced_model=MCMPreduced.ctl -seed=231”  I get an mcmp_results.csv file that lists the power as 0% at any number of individuals (0-40) at any significance level (5, 1 or 0.1%).

I have pasted the “full model” control stream below, as well as the version and option info.

Perhaps I’m doing something wrong, but I’m not sure what it is. Any help to get this to work is greatly appreciated (I’ll buy you a beer at the PAGE meeting).

Cheers,
Rob


—
Control stream
—
$PROB FULL MODEL

$INPUT C ID TIME AMT RATE EVID DV CMT

$DATA SIM.csv IGNORE=C
$SUBROUTINES ADVAN6 TOL=5

$MODEL COMP=(PLASMA, DEFDOS)
COMP=(PERI)

$PK

; NOTES
; -----
; MEAN BSA 1.76
; MEAN CRCL 96.9
; STANDARD DOSE 1000 MG

; BASIC PK
TVCL=THETA(1) ; TYPIAL VALUE CLEARANCE ML/MIN
CRCL=92.6*EXP(ETA(1)) ; RENAL FUNCTION (ML/MIN)
RENAL=THETA(2) ; EFFECT OF RENAL FUNCTION CL
CL=TVCL+RENAL*(CRCL/92.6)*EXP(ETA(2)) ; CL
TVV1=THETA(3) ; TYPICAL VALUE V1
BSA=1.76*EXP(ETA(3)) ; M2
BSAV=THETA(4) ; EFFECT OF BSA ON V1
V1=TVV1*(BSA**BSAV)*EXP(ETA(4)) ; V1
Q=THETA(5) ; INTERCOMP CLEARANCE
TVV2=THETA(6) ; TYPICAL VALUE V2
V2=TVV2*EXP(ETA(5)) ; V2

;MASS TRANSPORT
K12=Q/V1 ; FROM COMP1 TO COMP2
K21=Q/V2 ; FROM COMP2 TO COMP1
K10=CL/V1 ; CLEARANCE FROM COMP1

$DES
DADT(1)=-K12*A(1)-K10*A(1)+K21*A(2)
DADT(2)=-K21*A(2)+K12*A(1)

$ERROR
IPRED=F
Y=F+F*ERR(1)*THETA(7) ; PROP ERR

$THETA
43 ; TVCL1 (ML/MIN)
47.2 ; RENAL (ML/MIN)
6130 ; V1 (ML)
1.32 ; BSAV POWER
14.5 ; Q (ML/MIN)
3380 ; V2 (ML)
0.284 ; PROP RESIDUAL ERR


$OMEGA
0.1024 ; IIV CRCL
0.0372 ; IIV CL
0.0196 ; IIV BSA
0.0276 ; IIV V1
0.06 ; IIV V2


$SIGMA
1;         FIX

$SIM (2786) ONLYSIM
$TABLE FILE=MCMPFULLRES.TAB C ID TIME AMT RATE BSA CRCL DV PRED IPRED NOPRINT ONEHEADER




—
FROM version_and_option_info.txt
—

PsN version: 4.4.0
Run started: 2015-05-26 at 10:49
version_and_option_info.txt is overwitten if the run is restarted later using option -directory.
The original file from the first call is saved as original_version_and_option_info.txt.

Command:
/usr/bin/mcmp -full_model=MCMPfull.ctl -reduced_model=MCMPreduced.ctl -seed=231

NONMEM:
/opt/nm730

Actual values optional MCMP options (undefined values not listed):
-curve=1
-df=1
-n_bootstrap=10000
-significance_level=5
-target_power=98

Actual values optional PsN (common) options (undefined values not listed):
-abort_on_fail=0
-accepted_ofv_difference=0.5
-add_retries=0
-check_nmtran=0
-clean=1
-compress=0
-condition_number_limit=1000
-correlation_limit=0.85
-crash_restarts=4
-degree=0.1
-directory=/Users/robterheine/Data/PEMSIM/mcmp_dir2/
-display_iterations=0
-handle_crashes=1
-handle_msfo=0
-large_omega_cv_limit=0.8
-large_sigma_cv_limit=0.8
-large_theta_cv_limit=0.5
-last_est_complete=0
-lsf_sleep=3
-min_retries=0
-missing_data_token=-99
-near_bound_sign_digits=2
-near_zero_boundary_limit=0.01
-nice=19
-nm_output=ext,cov,cor,coi,phi
-nm_version=default
-nmfe=1
-nmqual=0
-nodes=0
-parafile=none
-picky=0
-prepend_model_file_name=0
-quick_summarize=0
-retries=0
-rplots=0
-run_on_lsf=0
-run_on_sge=0
-run_on_slurm=0
-run_on_torque=0
-run_on_ud=0
-run_on_zink=0
-seed=231
-send_email=0
-shrinkage=0
-sign_digits_off_diagonals=2
-significant_digits_accept=0
-standardised_output=0
-template_directory_rplots=/Library/Perl/5.18/PsN_4_4_0/R-scripts
-template_file_rplots=mcmp_default.R
-threads=5
-tweak_inits=1
-verbose=0

Het Radboudumc staat geregistreerd bij de Kamer van Koophandel in het handelsregister onder nummer 41055629.
The Radboud university medical center is listed in the Commercial Register of the Chamber of Commerce under file number 41055629.