From: hai le ba <*lebahai01*>

Date: Thu, 5 Nov 2020 11:58:58 +0100

Sorry, I've copied a wrong code of model.

The right is:

"$PK

MU_1= LOG(THETA(1))

KA=EXP(MU_1+ETA(1))

MU_2=LOG(THETA(2))+ THETA(4)*LOG(AGE/60.13)

CL= EXP(MU_2+ETA(2))

MU_3=LOG(THETA(3))+THETA(5)*LOG(WEI/66.49)

V=EXP(MU_3+ETA(3))

S2=V

IF (TIME.LT.12) TAD=TIME

IF (TIME.GE.12.AND.TIME.LT.24) TAD=TIME-12

IF (TIME.GE.12.AND.TIME.LT.36) TAD=TIME-24

IF (TIME.GE.36.AND.TIME.LT.48) TAD=TIME-36

$ERROR

EP1=EPS(1)

IPRED=F

IRES=DV-IPRED

W=F

IWRES=IRES/W

Y=IPRED+EPS(1)*W

Many thanks for your support!

Best regards,

Le jeu. 5 nov. 2020 à 11:15, hai le ba <lebahai01

rit :

*> Dear Sir Jakob and Jeroen,
*

*> Thanks for your reply.
*

*> In fact, i've a one compartment model, with two levels of random effect
*

*> (IIV, EPS) and covariate effect on CL, V.
*

*> $PK
*

*>
*

*> MU_1= LOG(THETA(1))
*

*>
*

*> KA=EXP(MU_1+ETA(1))
*

*>
*

*> MU_2=LOG(THETA(2)+ THETA(4)*LOG(AGE/60.13))
*

*> CL= EXP(MU_2+ETA(2))
*

*>
*

*> MU_3=LOG(THETA(3)+THETA(5)*LOG(WEI/66.49))
*

*> V=EXP(MU_3+ETA(3))
*

*>
*

*> S2=V
*

*> IF (TIME.LT.12) TAD=TIME
*

*> IF (TIME.GE.12.AND.TIME.LT.24) TAD=TIME-12
*

*> IF (TIME.GE.12.AND.TIME.LT.36) TAD=TIME-24
*

*> IF (TIME.GE.36.AND.TIME.LT.48) TAD=TIME-36
*

*>
*

*> $ERROR
*

*> EP1=EPS(1)
*

*> IPRED=F
*

*> IRES=DV-IPRED
*

*> W=F
*

*> IWRES=IRES/W
*

*> Y=IPRED+EPS(1)*W
*

*>
*

*> I've used this model to simulate the complete database (10 000 IDs). From
*

*> this database, the smaller dataset was randomly generated with respect to
*

*> the rule of one PK sample per each ID. After that, I want to check how
*

*> many IDs are necessary to get a good estimation for each method ( FOCEI,
*

*> SAEM, BAYES, composite (ITS/SAEM/IMP/BAYES))?
*

*>
*

*> For FOCEI, I can't get convergence.
*

*>
*

*> For SAEM, I've got some troubles with the stability for EPS when I tried
*

*> to change the SEED status?
*

*> Otherwise, the good estimations were obtained with RSE (10-20%) for the
*

*> other parameters.
*

*>
*

*> *

*> convergence for this setting of NBURN.
*

*> "
*

*> Convergence achieved
*

*>
*

*> STOCHASTIC PORTION WAS COMPLETED
*

*> REDUCED STOCHASTIC PORTION WAS COMPLETED"
*

*>
*

*> Could you give me some instructions?
*

*>
*

*> Many thanks in advance for your responses.
*

*> Best regards,
*

*> Hai, LE Ba
*

*> Ph.D Student
*

*> La faculté de Pharmacie - Aix Marseille université
*

*> Hanoi university of Pharmacy
*

*> Email: lebahai01 *

*> hailb *

*> bahai.le *

*>
*

*>
*

*> On Thu, Nov 5, 2020 at 10:43 AM Jakob Ribbing <
*

*> jakob.ribbing *

*>
*

*>> Dear LE Ba,
*

*>>
*

*>> You did not share much information on your model, except that you have
*

*>> one observations per subject and that EPS (or rather sigma) is estimated=
*

(I

*>> assume then a continuous endpoint).
*

*>> Is thisyour only level of random effect, so that you have no omega/eta
*

*>> for IOV or IIV? With one observations per subject it will be difficult t=
*

o

*>> find support for more than one level.
*

*>> And for a model with only residual error (no IIV), would not the FO
*

*>> Estimation method be sufficient, so why would you need to use SAEM for t=
*

his

*>> data/model?
*

*>>
*

*>> Best regards
*

*>>
*

*>> Jakob
*

*>>
*

*>>
*

*>>
*

*>> Jakob Ribbing, Ph.D.
*

*>>
*

*>> Senior Consultant, Pharmetheus AB
*

*>>
*

*>>
*

*>> Cell/Mobile: +46 (0)70 514 33 77
*

*>>
*

*>> Jakob.Ribbing *

*>>
*

*>> www.pharmetheus.com
*

*>>
*

*>> Phone, Office: +46 (0)18 513 328
*

*>>
*

*>> Uppsala Science Park, Dag Hammarskjölds väg 36B
*

*>> SE-752 37 Uppsala, Sweden
*

*>>
*

*>>
*

*>>
*

*>> This communication is confidential and is only intended for the use of
*

*>> the individual or entity to which it is directed. It may contain
*

*>> information that is privileged and exempt from disclosure under applicab=
*

le

*>> law. If you are not the intended recipient please notify us immediately.
*

*>> Please do not copy it or disclose its contents to any other person.
*

*>>
*

*>>
*

*>>
*

*>>
*

*>> On 5 Nov 2020, at 09:41, hai le ba <lebahai01 *

*>>
*

*>> Hello nmusers,
*

*>> I've tried to test the SAEM method on my dataset (1 sample for each ID)
*

*>> with different SEED status. Sometimes, I've got good results (with RSE
*

*>> <50%), but sometimes I can't get it.
*

*>>
*

*>> Example:
*

*>> $EST METHOD=SAEM INTERACTION NBURN=3000 NITER=500 AUTO=1 PRINT=
*

=100

*>> SEED=123456789
*

*>> $EST METHOD=IMP EONLY=1 PRINT=1 NITER=5 ISAMPLE=1000 MAPITER=
*

=0

*>> I've got EPS : 0.00064 (RSE=63%)
*

*>>
*

*>> but
*

*>> $EST METHOD=SAEM INTERACTION NBURN=3000 NITER=500 AUTO=1 PRINT=
*

=100

*>> SEED=123235489
*

*>> $EST METHOD=IMP EONLY=1 PRINT=1 NITER=5 ISAMPLE=1000 MAPITER=
*

=0

*>> I've got EPS : 0.0223 (RSE=18%)
*

*>>
*

*>> Could i trust on the good results (EPS=0.0223)? How can we control thi=
*

s

*>> problem?
*

*>>
*

*>> Thank you very much,
*

*>> Hai, LE Ba
*

*>> Ph.D Student
*

*>> La faculté de Pharmacie - Aix Marseille université
*

*>> Hanoi university of Pharmacy
*

*>> Email: lebahai01 *

*>> hailb *

*>> bahai.le *

*>>
*

*>>
*

*>>
*

Received on Thu Nov 05 2020 - 05:58:58 EST

Date: Thu, 5 Nov 2020 11:58:58 +0100

Sorry, I've copied a wrong code of model.

The right is:

"$PK

MU_1= LOG(THETA(1))

KA=EXP(MU_1+ETA(1))

MU_2=LOG(THETA(2))+ THETA(4)*LOG(AGE/60.13)

CL= EXP(MU_2+ETA(2))

MU_3=LOG(THETA(3))+THETA(5)*LOG(WEI/66.49)

V=EXP(MU_3+ETA(3))

S2=V

IF (TIME.LT.12) TAD=TIME

IF (TIME.GE.12.AND.TIME.LT.24) TAD=TIME-12

IF (TIME.GE.12.AND.TIME.LT.36) TAD=TIME-24

IF (TIME.GE.36.AND.TIME.LT.48) TAD=TIME-36

$ERROR

EP1=EPS(1)

IPRED=F

IRES=DV-IPRED

W=F

IWRES=IRES/W

Y=IPRED+EPS(1)*W

Many thanks for your support!

Best regards,

Le jeu. 5 nov. 2020 à 11:15, hai le ba <lebahai01

rit :

(I

o

his

le

=100

=0

=100

=0

s

Received on Thu Nov 05 2020 - 05:58:58 EST