From 63ebc7d3e71af252bf620d0ee6c7cae2bf7f4b5c Mon Sep 17 00:00:00 2001 From: Jeff Dickinson Date: Fri, 26 Jan 2024 13:20:52 -0600 Subject: [PATCH] Closes #94 PK Examples post (#99) * #94 PK Examples post * #94 run styler --------- Co-authored-by: Jeffrey Dickinson --- inst/WORDLIST.txt | 60 +++++- posts/2023-12-20_p_k__examples/appendix.R | 78 +++++++ .../p_k__examples.qmd | 196 ++++++++++++++++++ .../2023-12-20_p_k__examples/pharmaverse.png | Bin 0 -> 21533 bytes posts/2023-12-20_p_k__examples/pk_spec.xlsx | Bin 0 -> 40884 bytes 5 files changed, 333 insertions(+), 1 deletion(-) create mode 100644 posts/2023-12-20_p_k__examples/appendix.R create mode 100644 posts/2023-12-20_p_k__examples/p_k__examples.qmd create mode 100644 posts/2023-12-20_p_k__examples/pharmaverse.png create mode 100644 posts/2023-12-20_p_k__examples/pk_spec.xlsx diff --git a/inst/WORDLIST.txt b/inst/WORDLIST.txt index db8fcd2e..0021a959 100644 --- 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 new file mode 100644 index 00000000..ece5203f --- /dev/null +++ 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 new file mode 100644 index 00000000..8184a085 --- /dev/null +++ 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" +--- + + + +```{r setup, include=FALSE} +long_slug <- "2023-12-20_p_k__examples" +# renv::use(lockfile = "renv.lock") +``` + + + +# 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! + + + +```{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 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