Reg.Flagnext usage Dynamic Dosing simulation (not working)

[Ravua1992]

Hello,

I want to understand how to capture the time and event of dosing in Dynamic dosing using reg. flag next () option. after running a test simulation when I try to filter out EVID >0 I get an empty dataset. Is the right way to use this? Thank you.

library(mrgsolve)

code <- '

$PROB Example of Dynamic Dosing within Mrgsolve

$PLUGIN evtools

$PARAM

// Typical model parameters

VC = 483.8
CRCL = 1.0
CLH = 22.7
ALC0 = 1.0
KOUT = 0.00065 // ZZZ c
EMAX = 457.0

// Covariates and individual parameters

WTKG = 50
EC50 = 1

// Dosing parameters

DOSE_CMT = 1
DOSE_NDOSE = 7
DOSE_LCYCLE1=504
DOSE_ENDTIME= 504*3
// Solver parameters

ATOL = 1E-8 // Default


$CMT 

CENT
PD

$GLOBAL

evt::regimen reg; // create dosing regimen object

$MAIN

// Dynamic Dosing

double DOSEMG_IN = 10.0;
//if(WTKG < 50.0){  // ZZZ DUMMY: Update conditions and dosage based on weight buckets (starting/default dosage for first dose administered to each subject)

if(NEWIND <= 1){ // do once for each subject

  reg.init(self);          // initialize dosing regimen for dynamic dosing
  reg.amt(DOSEMG_IN);      // dose amt (mg)
  reg.cmt(DOSE_CMT);       // dosing cmt
  reg.ii(DOSE_LCYCLE1);    // within cycle dosing interval
  reg.until(DOSE_ENDTIME); // last possible dose of simulation
  reg.flagnext();          // flag time of each dose to ensure dynamic dosing if the time is not already captured within the observation time grid (i.e., EVID = 0)
  
  double DRUG_ON = 1.0;
  double POSTPONE = 0.0;
  double TPOSTPONE = 0.0;
}

double DOSE_OUT = reg.amt();

// PK and PK-PD Model

double CLR=CRCL;
double CL = CLH + CLR;
double KE = CL/VC;

double KIN = ALC0*KOUT;
PD_0 = ALC0;

$ODE

// PK and PK-PD Model

dxdt_CENT = -KE*CENT;
double CP = 1000.0*(CENT/VC); // unit conversion mg/L to ng/mL ?

if(CP < ATOL){ // concentration will oscillate and become negative when near absolute tolerance
  CP = 0.0;
}

double EFFECT = 0.0;
if(CP > 0){
  EFFECT = EMAX*CP/(EC50+CP);
}
dxdt_PD = KIN - KOUT*(1.0+EFFECT)*PD;

$OMEGA 0.0 // placeholder

$ERROR

double REPEAT = std::floor(TIME/504.0)+1.0; // calculate current repeat (i.e., year)
double REPEAT_TIME = TIME - (REPEAT-1.0)*504.0;

double CYCLE = std::floor(REPEAT_TIME/504.0)+1.0; // Each cycle is 504 hours (3 weeks)
double CYCLE_TIME = REPEAT_TIME - (CYCLE-1.0)*504.0;
double DOSEN = std::floor(CYCLE_TIME/168.0)+1.0; // Smallest interval is 168 hours (1 week)
double DOSE_TIME = CYCLE_TIME - (DOSEN-1.0)*168.0;

if(TIME == 504.00) {
  reg.amt(DOSEMG_IN/2.0);
}


if(TIME == 1008.00) {
  reg.amt(DOSEMG_IN/2.0);
}

reg.execute(); // execute the dosing regimen created within mrgsolve code

$TABLE

double PD1 = PD;
double PD_BX = (pow(PD1, 0.2) - 1.0)/0.2; // Calculating PD_BX here

$CAPTURE WTKG EC50 CP REPEAT CYCLE DOSEN REPEAT_TIME CYCLE_TIME DOSE_TIME DRUG_ON DOSE_OUT POSTPONE TPOSTPONE PD_BX  EVID

'
mod<-mcode('example_test',code)

idata <- expand.idata(ID = 1:3)

set.seed(12345)

out <- mrgsim(
  mod, 
  idata = idata, 
  end = 9*168
)

plot(out,CP+PD+CYCLE_TIME+EVID~time)   

head(out)

out %>% filter(EVID>0)