Closes #94 PK Examples post (#99)

* #94 PK Examples post * #94 run styler --------- Co-authored-by: Jeffrey Dickinson <[email protected]>
pharmaverse · Jan 26, 2024 · 63ebc7d · 63ebc7d
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diff --git a/inst/WORDLIST.txt b/inst/WORDLIST.txt
@@ -500,6 +500,64 @@ VSDY
 VSORRES
 VSSEQ
 VSTESTCD
+adnca
+adppk
+ADPPK
+AETHNIC
+AETHNICN
+ARMCD
+BILI
+BILIBL
+bmi
+BMIBL
+bsa
+BSABL
+CKD
+codelist
+COHORTC
+COUNTRYL
+COUNTRYN
+covar
+CRCL
+CRCLBL
+creat
+CREAT
+CREATBL
+creatu
+egfr
+EGFRBL
+EPI
+EXDOSFRM
+EXROUTE
+FORMN
+HTBL
+labsbl
+LBBLFL
+LBSTRESN
+LBTESTCD
+LBTESTCDB
+metatools
+Mosteller
+pc
+pharmacokinetic
+pharmaverseadam
+poppk
+preconfigured
+RACEN
+ROUTEN
+SEXN
+SITEIDN
+STUDYIDN
+SUBJID
+SUBJIDN
+SUBJTYP
+SUBJTYPC
+TBILBL
+USUBJIDN
+VSBLFL
+vslb
+VSSTRESN
+WTBL
 analytics
 Analytics
 csp
@@ -514,7 +572,7 @@ traceRedir
 pKobZqjlXChj
 si
 vehIoJgdA
-youtuABLFL
+ABLFL
 admiraldisc
 admiraldiscovery
 advs

diff --git a/posts/2023-12-20_p_k__examples/appendix.R b/posts/2023-12-20_p_k__examples/appendix.R
@@ -0,0 +1,78 @@
+# markdown helpers --------------------------------------------------------
+
+markdown_appendix <- function(name, content) {
+  paste(paste("##", name, "{.appendix}"), " ", content, sep = "\n")
+}
+markdown_link <- function(text, path) {
+  paste0("[", text, "](", path, ")")
+}
+
+
+
+# worker functions --------------------------------------------------------
+
+insert_source <- function(repo_spec, name,
+                          collection = "posts",
+                          branch = "main",
+                          host = "https://github.com",
+                          text = "source code") {
+  path <- paste(
+    host,
+    repo_spec,
+    "tree",
+    branch,
+    collection,
+    name,
+    "code_sections.qmd",
+    sep = "/"
+  )
+  return(markdown_link(text, path))
+}
+
+insert_timestamp <- function(tzone = Sys.timezone()) {
+  time <- lubridate::now(tzone = tzone)
+  stamp <- as.character(time, tz = tzone, usetz = TRUE)
+  return(stamp)
+}
+
+insert_lockfile <- function(repo_spec, name,
+                            collection = "posts",
+                            branch = "main",
+                            host = "https://github.com",
+                            text = "R environment") {
+  path <- paste(
+    host,
+    repo_spec,
+    "tree",
+    branch,
+    collection,
+    name,
+    "renv.lock",
+    sep = "/"
+  )
+  return(markdown_link(text, path))
+}
+
+
+
+# top level function ------------------------------------------------------
+
+insert_appendix <- function(repo_spec, name, collection = "posts") {
+  appendices <- paste(
+    markdown_appendix(
+      name = "Last updated",
+      content = insert_timestamp()
+    ),
+    " ",
+    markdown_appendix(
+      name = "Details",
+      content = paste(
+        insert_source(repo_spec, name, collection),
+        insert_lockfile(repo_spec, name, collection),
+        sep = ", "
+      )
+    ),
+    sep = "\n"
+  )
+  knitr::asis_output(appendices)
+}
diff --git a/posts/2023-12-20_p_k__examples/p_k__examples.qmd b/posts/2023-12-20_p_k__examples/p_k__examples.qmd
@@ -0,0 +1,196 @@
+---
+title: "PK Examples"
+author:
+  - name: Jeff Dickinson
+description: "Explore PK ADaM Examples on Pharmaverse Examples Page"
+date: "2023-12-20"
+# please do not use any non-default categories.
+# You can find the default categories in the repository README.md
+categories: [community, admiral, metacore, metatools, xportr]
+# feel free to change the image
+image: "pharmaverse.png"
+---
+
+<!--------------- typical setup ----------------->
+
+```{r setup, include=FALSE}
+long_slug <- "2023-12-20_p_k__examples"
+# renv::use(lockfile = "renv.lock")
+```
+
+<!--------------- post begins here ----------------->
+
+# Pharmaverse PK Examples
+
+A new [pharmaverse examples website](https://pharmaverse.github.io/examples){target="_blank"} has some exciting new features to explore.
+
+One of these is the ability to launch Posit Cloud to explore the example code and make your own modifications.
+This interactive Posit Cloud environment is preconfigured with all required package installations.
+Click here: [Launch Posit Cloud](https://posit.cloud/content/7279124){target="_blank"} to explore the examples code.
+
+This sample code here is based on the Population PK Analysis Data (ADPPK) model which follows the recently released [CDISC Implementation Guide](https://www.cdisc.org/standards/foundational/adam/basic-data-structure-adam-poppk-implementation-guide-v1-0){target="_blank"}.
+
+Population PK models generally make use of nonlinear mixed effects models that require numeric variables.
+The data used in the models will include both dosing and concentration records, relative time variables, and numeric covariate variables.
+For more details see the `{admiral}` [vignette](https://pharmaverse.github.io/admiral/articles/pk_adnca.html){target="_blank"}.
+
+## First Load Packages
+
+First we will load the packages required for our project.
+We will use `{admiral}` for the creation of analysis data.
+`{admiral}` requires `{dplyr}`, `{lubridate}` and `{stringr}`.
+We will use `{metacore}` and `{metatools}` to store and manipulate metadata from our specifications.
+We will use `{xportr}` to perform checks on the final data and export to a transport file.
+
+The source SDTM data will come from the CDISC pilot study data stored in `{pharmaversesdtm}` and the ADaM ADSL data will come from `{pharmaverseadam}`.
+
+```{r echo=TRUE, message=FALSE}
+#| label: Load Packages
+# Load Packages
+library(admiral)
+library(dplyr)
+library(lubridate)
+library(stringr)
+library(metacore)
+library(metatools)
+library(xportr)
+library(readr)
+library(pharmaversesdtm)
+library(pharmaverseadam)
+```
+
+## Next Load Specifications for Metacore
+
+We have saved our specifications in an Excel file and will load them into `{metacore}` with the `metacore::spec_to_metacore()` function.
+
+```{r echo=TRUE, message=FALSE}
+#| label: Load Specs
+#| warning: false
+# ---- Load Specs for Metacore ----
+metacore <- spec_to_metacore("pk_spec.xlsx") %>%
+  select_dataset("ADPPK")
+```
+
+## Load Source Datasets
+
+We will load our SDTM data from `{pharmaversesdtm}`.
+The main components of the Population PK will be exposure data from `EX` and pharmacokinetic concentration data from `PC`.
+Here we will use `ADSL` from `{pharmaverseadam}` for baseline characteristics and we will derive additional baselines from vital signs `VS` and laboratory data `LB`.
+
+```{r}
+#| label: Load Source
+# ---- Load source datasets ----
+# Load PC, EX, VS, LB and ADSL
+data("pc")
+data("ex")
+data("vs")
+data("lb")
+data("adsl")
+
+ex <- convert_blanks_to_na(ex)
+pc <- convert_blanks_to_na(pc)
+vs <- convert_blanks_to_na(vs)
+lb <- convert_blanks_to_na(lb)
+```
+
+## Derive Covariates Using `{metatools}`
+
+In this step we will create our numeric covariates using the `metatools::create_var_from_codelist()` function.
+
+```{r}
+#| label: Covariates
+#---- Derive Covariates ----
+# Include numeric values for STUDYIDN, USUBJIDN, SEXN, RACEN etc.
+
+covar <- adsl %>%
+  create_var_from_codelist(metacore, input_var = STUDYID, out_var = STUDYIDN) %>%
+  create_var_from_codelist(metacore, input_var = SEX, out_var = SEXN) %>%
+  create_var_from_codelist(metacore, input_var = RACE, out_var = RACEN) %>%
+  create_var_from_codelist(metacore, input_var = ETHNIC, out_var = AETHNIC) %>%
+  create_var_from_codelist(metacore, input_var = AETHNIC, out_var = AETHNICN) %>%
+  create_var_from_codelist(metacore, input_var = ARMCD, out_var = COHORT) %>%
+  create_var_from_codelist(metacore, input_var = ARMCD, out_var = COHORTC) %>%
+  create_var_from_codelist(metacore, input_var = COUNTRY, out_var = COUNTRYN) %>%
+  create_var_from_codelist(metacore, input_var = COUNTRY, out_var = COUNTRYL) %>%
+  mutate(
+    STUDYIDN = as.numeric(word(USUBJID, 1, sep = fixed("-"))),
+    SITEIDN = as.numeric(word(USUBJID, 2, sep = fixed("-"))),
+    USUBJIDN = as.numeric(word(USUBJID, 3, sep = fixed("-"))),
+    SUBJIDN = as.numeric(SUBJID),
+    ROUTE = unique(ex$EXROUTE),
+    FORM = unique(ex$EXDOSFRM),
+    REGION1 = COUNTRY,
+    REGION1N = COUNTRYN,
+    SUBJTYPC = "Volunteer",
+  ) %>%
+  create_var_from_codelist(metacore, input_var = FORM, out_var = FORMN) %>%
+  create_var_from_codelist(metacore, input_var = ROUTE, out_var = ROUTEN) %>%
+  create_var_from_codelist(metacore, input_var = SUBJTYPC, out_var = SUBJTYP)
+```
+
+### Derive Additional Baselines
+
+Next we add additional baselines from vital signs and laboratory data.
+Several common variables are computed using some of the built in functions in `{admiral}`.
+
+```{r}
+#| label: Baselines
+
+labsbl <- lb %>%
+  filter(LBBLFL == "Y" & LBTESTCD %in% c("CREAT", "ALT", "AST", "BILI")) %>%
+  mutate(LBTESTCDB = paste0(LBTESTCD, "BL")) %>%
+  select(STUDYID, USUBJID, LBTESTCDB, LBSTRESN)
+
+covar_vslb <- covar %>%
+  derive_vars_merged(
+    dataset_add = vs,
+    filter_add = VSTESTCD == "HEIGHT",
+    by_vars = exprs(STUDYID, USUBJID),
+    new_vars = exprs(HTBL = VSSTRESN)
+  ) %>%
+  derive_vars_merged(
+    dataset_add = vs,
+    filter_add = VSTESTCD == "WEIGHT" & VSBLFL == "Y",
+    by_vars = exprs(STUDYID, USUBJID),
+    new_vars = exprs(WTBL = VSSTRESN)
+  ) %>%
+  derive_vars_transposed(
+    dataset_merge = labsbl,
+    by_vars = exprs(STUDYID, USUBJID),
+    key_var = LBTESTCDB,
+    value_var = LBSTRESN
+  ) %>%
+  mutate(
+    BMIBL = compute_bmi(height = HTBL, weight = WTBL),
+    BSABL = compute_bsa(
+      height = HTBL,
+      weight = HTBL,
+      method = "Mosteller"
+    ),
+    CRCLBL = compute_egfr(
+      creat = CREATBL, creatu = "SI", age = AGE, weight = WTBL, sex = SEX,
+      method = "CRCL"
+    ),
+    EGFRBL = compute_egfr(
+      creat = CREATBL, creatu = "SI", age = AGE, weight = WTBL, sex = SEX,
+      method = "CKD-EPI"
+    )
+  ) %>%
+  rename(TBILBL = BILIBL)
+```
+
+This covariate section of the code will be combined with the dosing and observation records from `EX` and `PC`.
+
+The rest of the code can be seen on the [pharmaverse examples website](https://pharmaverse.github.io/examples){target="_blank"} or in the [Posit Cloud environment](https://posit.cloud/content/7279124){target="_blank"}.
+
+Happy exploring!
+
+<!--------------- appendices go here ----------------->
+
+```{r, echo=FALSE}
+source("appendix.R")
+insert_appendix(
+  repo_spec = "pharmaverse/blog",
+  name = long_slug
+)
+```
diff --git a/posts/2023-12-20_p_k__examples/pharmaverse.png b/posts/2023-12-20_p_k__examples/pharmaverse.png
diff --git a/posts/2023-12-20_p_k__examples/pk_spec.xlsx b/posts/2023-12-20_p_k__examples/pk_spec.xlsx