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R pacakge: ncarbe

Sungpil Han 2018-06-07

ncarbe R package

NonCompart 패키지를 사용해서 2x2 생동성시험의 분산분석 등을 손쉽게 해주는 패키지입니다. 지원하는 계산은 다음과 같습니다.

parameters statistics
AUClast Analysis of variance, between and within subject variability, least square means, confidence interval, and sample size
Cmax Analysis of variance, between and within subject variability, least square means, confidence interval, and sample size
Tmax Wilcoxon Signed-Rank Test and Hodges-Lehmann Estimate

설치

install.packages('devtools')
devtools::install_github('asancpt/ncarbe')

실행

예제 데이타 (시뮬레이션 데이타)

2x2 생동성시험 디자인으로 36명의 데이타를 생성하여 시뮬레이션 한 것입니다. (배균섭 교수님 pk1coma.R 사용)

file <- system.file('example', 'beConc.csv', package = 'ncarbe')
concData <- read.csv(file, as.is = TRUE)
head(concData)
##   SUBJ GRP PRD TRT nTIME TIME   CONC
## 1    1  RT   1   R  0.00 0.02  63.42
## 2    1  RT   1   R  0.25 0.24 432.76
## 3    1  RT   1   R  0.50 0.51 622.88
## 4    1  RT   1   R  0.75 0.80 809.93
## 5    1  RT   1   R  1.00 1.02 824.34
## 6    1  RT   1   R  2.00 2.04 602.22

자료 탐색

그림을 그려보면 다음과 같습니다.

library(ggplot2)
library(dplyr)

concData %>% 
  ggplot(aes(x = TIME, y = CONC, group = TRT, color = TRT)) +
  geom_line(size = 0.5, alpha = 0.8) +
  geom_point(size = 1, alpha = 0.5) +
  xlab('Time (hr)') +
  ylab('Concentrationg (ng/mL)') +
  facet_wrap( ~ SUBJ, ncol = 4)

생동성 분석

beNCA() 함수를 사용하여 분석한 결과입니다.

method = 'kbe'

library(ncarbe)
beNCA(concData)     # method = 'kbe'
## 
## 
## [AUClast]
## 
## $`Analysis of Variance`
##                        SS DF        MS        F           p
## SUBJECT        35.7817072 35 1.0223345 1.854676 0.037320327
## GROUP           1.1390308  1 1.1390308 1.117900 0.297825788
## SUBJECT(GROUP) 34.6426764 34 1.0189022 1.848449 0.038831903
## PERIOD          4.1989873  1 4.1989873 7.617625 0.009244748
## DRUG            0.7021705  1 0.7021705 1.273848 0.266947114
## ERROR          18.7414811 34 0.5512200       NA          NA
## TOTAL          58.9756619 71        NA       NA          NA
## 
## $`Between and Within Subject Variability`
##                                 Between Subject Within Subject
## Variance Estimate                     0.2338411        0.55122
## Coefficient of Variation, CV(%)      51.3267693       85.75365
## 
## $`Least Square Means`
##                 Reference Drug Test Drug
## Geometric Means       31.20441   25.5401
## 
## $`90% Confidence Interval`
##                  Lower Limit Point Estimate Upper Limit
## 90% CI for Ratio   0.6062815      0.8184771     1.10494
## 
## $`Sample Size`
##                       True Ratio=1 True Ratio=Point Estimate
## 80% Power Sample Size           96                      6538
## 
## 
## 
## [Cmax]

## Warning in sqrt(exp(sig2b) - 1): NaN이 생성되었습니다

## $`Analysis of Variance`
##                        SS DF        MS         F          p
## SUBJECT        22.1199814 35 0.6319995 0.6475704 0.89703843
## GROUP           0.2047080  1 0.2047080 0.3175901 0.57675784
## SUBJECT(GROUP) 21.9152734 34 0.6445669 0.6604475 0.88422171
## PERIOD          3.6728929  1 3.6728929 3.7633843 0.06071806
## DRUG            0.1136911  1 0.1136911 0.1164922 0.73497096
## ERROR          33.1824629 34 0.9759548        NA         NA
## TOTAL          58.9756619 71        NA        NA         NA
## 
## $`Between and Within Subject Variability`
##                                 Between Subject Within Subject
## Variance Estimate                     -0.165694      0.9759548
## Coefficient of Variation, CV(%)             NaN    128.5962569
## 
## $`Least Square Means`
##                 Reference Drug Test Drug
## Geometric Means       26.30688  28.51506
## 
## $`90% Confidence Interval`
##                  Lower Limit Point Estimate Upper Limit
## 90% CI for Ratio   0.7270811       1.083939    1.615946
## 
## $`Sample Size`
##                       True Ratio=1 True Ratio=Point Estimate
## 80% Power Sample Size          169                       298
## 
## 
## 
## [Tmax]
## 
## $`Wilcoxon Signed-Rank Test`
##   p-value 
## 0.3286283 
## 
## $`Hodges-Lehmann Estimate`
##                            Lower Limit Point Estimate Upper Limit
## 90% Confidence Interval       -2.00000         1.0000      4.0000
## 90% Confidence Interval(%)    87.11261       106.4437    125.7748

method = 'nlme'

beNCA(concData, method = 'nlme')
## $Confidence.Interval
## # A tibble: 2 x 4
##   parameter `Lower limit of 90% CI` `T/R ratio` `Upper limit of 90% CI`
##   <chr>                       <dbl>       <dbl>                   <dbl>
## 1 Cmax                        0.753       1.08                     1.56
## 2 AUClast                     0.606       0.818                    1.10

Reference

  • Bae K (2018). NonCompart: Noncompartmental Analysis for Pharmacokinetic Data. R package version 0.4.2, https://CRAN.R-project.org/package=NonCompart.

  • Bae K, Han S (2018). ncarbe: Perform BE Test Using NonCompart Package. R package version 0.1.1.

  • Pinheiro J, Bates D, DebRoy S, Sarkar D, R Core Team (2018). nlme: Linear and Nonlinear Mixed Effects Models. R package version 3.1-137, https://CRAN.R-project.org/package=nlme.

devtools::session_info()

devtools::session_info()
## Session info -------------------------------------------------------------

##  setting  value                       
##  version  R version 3.5.0 (2018-04-23)
##  system   x86_64, darwin17.5.0        
##  ui       unknown                     
##  language (EN)                        
##  collate  C                           
##  tz       Asia/Seoul                  
##  date     2018-06-07

## Packages -----------------------------------------------------------------

##  package    * version date       source        
##  assertthat   0.2.0   2017-04-11 CRAN (R 3.5.0)
##  backports    1.1.2   2017-12-13 CRAN (R 3.5.0)
##  base       * 3.5.0   2018-05-02 local         
##  bindr        0.1.1   2018-03-13 CRAN (R 3.5.0)
##  bindrcpp   * 0.2.2   2018-03-29 CRAN (R 3.5.0)
##  cli          1.0.0   2017-11-05 CRAN (R 3.5.0)
##  colorspace   1.3-2   2016-12-14 CRAN (R 3.5.0)
##  compiler     3.5.0   2018-05-02 local         
##  crayon       1.3.4   2017-09-16 CRAN (R 3.5.0)
##  datasets   * 3.5.0   2018-05-02 local         
##  devtools     1.13.5  2018-02-18 CRAN (R 3.5.0)
##  digest       0.6.15  2018-01-28 CRAN (R 3.5.0)
##  dplyr      * 0.7.5   2018-05-19 CRAN (R 3.5.0)
##  evaluate     0.10.1  2017-06-24 CRAN (R 3.5.0)
##  ggplot2    * 2.2.1   2016-12-30 CRAN (R 3.5.0)
##  glue         1.2.0   2017-10-29 CRAN (R 3.5.0)
##  graphics   * 3.5.0   2018-05-02 local         
##  grDevices  * 3.5.0   2018-05-02 local         
##  grid         3.5.0   2018-05-02 local         
##  gtable       0.2.0   2016-02-26 CRAN (R 3.5.0)
##  htmltools    0.3.6   2017-04-28 CRAN (R 3.5.0)
##  knitr        1.20    2018-02-20 CRAN (R 3.5.0)
##  labeling     0.3     2014-08-23 CRAN (R 3.5.0)
##  lattice      0.20-35 2017-03-25 CRAN (R 3.5.0)
##  lazyeval     0.2.1   2017-10-29 CRAN (R 3.5.0)
##  magrittr     1.5     2014-11-22 CRAN (R 3.5.0)
##  memoise      1.1.0   2017-04-21 CRAN (R 3.4.2)
##  methods    * 3.5.0   2018-05-02 local         
##  munsell      0.4.3   2016-02-13 CRAN (R 3.5.0)
##  ncarbe     * 0.1.1   2018-06-07 local         
##  nlme         3.1-137 2018-04-07 CRAN (R 3.5.0)
##  NonCompart   0.4.2   2018-05-17 CRAN (R 3.5.0)
##  pillar       1.2.3   2018-05-25 CRAN (R 3.5.0)
##  pkgconfig    2.0.1   2017-03-21 CRAN (R 3.5.0)
##  plyr         1.8.4   2016-06-08 CRAN (R 3.5.0)
##  purrr        0.2.5   2018-05-29 CRAN (R 3.5.0)
##  R6           2.2.2   2017-06-17 CRAN (R 3.5.0)
##  Rcpp         0.12.17 2018-05-18 CRAN (R 3.5.0)
##  rlang        0.2.1   2018-05-30 CRAN (R 3.5.0)
##  rmarkdown    1.9     2018-03-01 CRAN (R 3.5.0)
##  rprojroot    1.3-2   2018-01-03 CRAN (R 3.5.0)
##  scales       0.5.0   2017-08-24 CRAN (R 3.5.0)
##  stats      * 3.5.0   2018-05-02 local         
##  stringi      1.2.2   2018-05-02 CRAN (R 3.5.0)
##  stringr      1.3.1   2018-05-10 CRAN (R 3.5.0)
##  tibble       1.4.2   2018-01-22 CRAN (R 3.5.0)
##  tidyselect   0.2.4   2018-02-26 CRAN (R 3.5.0)
##  tools        3.5.0   2018-05-02 local         
##  utf8         1.1.4   2018-05-24 CRAN (R 3.5.0)
##  utils      * 3.5.0   2018-05-02 local         
##  withr        2.1.2   2018-03-15 CRAN (R 3.5.0)
##  yaml         2.1.19  2018-05-01 CRAN (R 3.5.0)