README.Rmd

---
title: "NONMEM workshop"
author: "Sungpil Han, Kyun-Seop Bae"
date: "`r Sys.Date()`"
output:
  html_document:
    df_print: paged
editor_options:
  chunk_output_type: console
---

```{r setup, include = FALSE}
library(knitr)
library(readr)
library(dplyr)
library(tidyr)
library(purrr)
library(nmw)
library(lattice)

inputFirst <- read_csv("result/inputFirst.csv", 
                       col_names = c('name', 'value'), 
                       skip = 1) %>% 
  print()

input <- inputFirst %>% 
  spread(name, value)

NMDataset <- input$Dataset
METHOD <- input$Method 
nTheta <- as.numeric(input$nTheta)
nEta <- as.numeric(input$nEta)
nEps <- as.numeric(input$nEps)

# Initial Value: Theta
THETAinit <- as.numeric(unlist(strsplit(input$THETAinit, split=",")))
# Initial Value: Omega (Eta)
OMinit <- matrix(as.numeric(unlist(strsplit(input$OMinit, split=","))), 
                 nrow=nEta, 
                 ncol=nEta)
# Initial Value: Sigma (Epsilon)
SGinit <- matrix(as.numeric(unlist(strsplit(input$SGinit, split=","))), 
                 nrow=nEps, 
                 ncol=nEps)

LB <- rep(0, nTheta)
UB <- rep(1000000, nTheta)
```

![Cover](cover.jpg)

<https://github.com/asancpt/edison-nmw>  
license: GPL-3

## Introduction

NONMEM Workshop 2017, 2018에서 사용된 nmw 패키지를 사용한 Edison 사이언스 앱입니다.

## Result

A table (head) and a figure of input dataset is shown below.

### Initial values

```{r}
kable(inputFirst, format = "markdown")
```

### Input Table

```{r include = FALSE}
#enableJIT(3)
##setwd("C:/NMW2017/03-Emax")

if (NMDataset == "Emax"){
  DataFile <- "03-Emax/SimData.CSV"
  DataAll <- read.csv(DataFile)
} else if (NMDataset == "Theoph") {
  
  DataAll <- datasets::Theoph %>% 
    select(Subject, Time, conc) %>% 
    set_names('ID', 'TIME', 'DV') %>% 
    print()
}
```

```{r}
kable(head(DataAll, n = 20), caption = "input data", format = "markdown")
```

### Figure

```{r figure, include = TRUE}
if (NMDataset == "Emax") xyplot(DV ~ log(CE) | ID, data=DataAll, type="b")
if (NMDataset == "Theoph") {
  xyplot(DV~TIME|ID, 
         data=DataAll, 
         type="b",
         index.cond=list(order(as.numeric(levels(unique(DataAll$ID))))))
}
```

### Method Calculation

- Dataset: `r NMDataset`
- Method: `r METHOD`

```{r ZERO}
PREDFILE <- ifelse(NMDataset == "Emax", "03-Emax/PRED.R", "04-THEO/PRED.R")
source(PREDFILE)

FGD <- deriv(expr = ~ DOSE/
               (TH2*exp(ETA2)) * 
               TH1*exp(ETA1)/
               (TH1*exp(ETA1) - TH3*exp(ETA3)) *
               (exp(-TH3*exp(ETA3)*TIME)-exp(-TH1*exp(ETA1)*TIME)),
             namevec = c("ETA1","ETA2","ETA3"),
             function.arg = c("TH1", "TH2", "TH3", 
                              "ETA1", "ETA2", "ETA3", 
                              "DOSE", "TIME"),
             func=TRUE, 
             hessian=TRUE)

H <- deriv(~F + F*EPS1 + EPS2, c("EPS1", "EPS2"), 
           function.arg=c("F", "EPS1", "EPS2"), 
           func=TRUE)

InitPara <- nmw::InitStep(DataAll, 
                          THETAinit=THETAinit, 
                          OMinit=OMinit, 
                          SGinit=SGinit, 
                          LB=LB, 
                          UB=UB, 
                          Pred=PRED,
                          METHOD=METHOD)
(EstRes = EstStep()) # 0.6200359 secs, 0.4930282 secs
(CovRes = CovStep())

#PostHocEta() # FinalPara from EstStep()
#get("EBE", envir=e)
```

## Appendix

### Examples for Initial Values

#### Emax

```
PRED = function(THETA, ETAi, DATAi)
{
CE   = DATAi[,"CE"]
CE50 = as.numeric(THETA[1] * exp(ETAi[1]))
BASE = as.numeric(THETA[2])
F    = BASE * (1 - CE/(CE50 + CE))
G1   = BASE * CE * CE50 / (CE50 + CE)^2
H1   = rep(1, nrow(DATAi))
D11  = (-2*CE50/(CE + CE50) + 1) * G1

return(cbind(F, G1, H1, D11))
}

nTheta = 2
nEta = 1
nEps = 1

THETAinit = 10, 100
OMinit = 0.2
SGinit = 1
```

#### Theoph (ZERO, CONC)
```
nTheta = 3
nEta = 3
nEps = 2

THETAinit = 2, 50, 0.1
OMinit = 0.2, 0.1, 0.1, 0.1, 0.2, 0.1, 0.1, 0.1, 0.2
SGinit = 0.1, 0, 0, 0.1
```

#### Theoph (LAPL)

```
THETAinit = 4, 50, 0.2
```

The other values are the same with those of `Theoph (ZERO, CONC)`.

## References

`r paste(read_lines('bibliography.txt'), collapse = "\n")`