Merge pull request #222 from pharmaverse/211-feature-request-add-the-lumipulse-g-ptau217ß-amyloid-1-42-plasma-ratio-in-lb_neuro

Closes #211 Feature request add the lumipulse G ptau217 B amyloid 1-42 plasma ratio in lb_neuro

Author: Lina2689

NEWS.md

@@ -16,7 +16,7 @@
     - `ag_neuro`
     - `lb_neuro`
 
-- Updated `rs_onco_pcwg3` to correct the misclassification of `PDu` and to remove the `TMRESP` records.  (#193)
+- Updated `rs_onco_pcwg3` to correct the misclassification of `PDu` and to remove the `TMRESP` records. (#193)
 
 - Added `lb_onco_pcwg3` dataset which contains PSA measurements for PCWG criteria. (#197)
 
@@ -34,6 +34,8 @@
 
 - Generated different sites for the development and released versions of the package. (#207)
 
+- Added the Lumipulse G pTau217, β-Amyloid 1-42 Plasma and their Ratio in `lb_neuro`. (#211)
+
 - Updated the pull request template to include the corrected package website name. (#223)
 
 </details>

R/lb_neuro.R

@@ -38,9 +38,12 @@
 #'   }
 #'
 #' @source Constructed by {admiralneuro} developers
-#' @details Contains a set of 1 unique Test Short Name and Test Name: \tabular{ll}{
+#' @details Contains a set of 4 unique Test Short Names and Test Names: \tabular{ll}{
 #'   \strong{LBTESTCD} \tab \strong{LBTEST} \cr
-#'   ASYNASAA \tab Alpha Synuclein Seed Amplification Assay (CSF)
+#'   AMYLB42  \tab Lumipulse G Beta-Amyloid 1-42-N Plasma             \cr
+#'   ASYNASAA \tab Alpha Synuclein Seed Amplification Assay (CSF)     \cr
+#'   PTAB42R  \tab Lumipulse G pTau 217/Beta-Amyloid 1-42 Plasma Ratio\cr
+#'   PTAU217  \tab Lumipulse G pTau 217 Plasma
 #' }
 
 "lb_neuro"

data-raw/lb_neuro.R

@@ -4,14 +4,18 @@
 # Load libraries
 library(admiral)
 library(dplyr)
+library(cli)
+
+# Print numeric numbers in regular decimal format
+options(scipen = 999)
 
 # Read input data
 dm_neuro <- pharmaversesdtm::dm_neuro
 nv_neuro <- pharmaversesdtm::nv_neuro
-adsl_neuro <- admiralneuro::adsl_neuro
 
 # Convert blank to NA
 dm_neuro <- convert_blanks_to_na(dm_neuro)
+nv_neuro <- convert_blanks_to_na(nv_neuro)
 
 # Select patients from DM Neuro only (following adsl_neuro.R pattern)
 # Separate randomized group to identify which subjects don't have planned study days
@@ -40,23 +44,22 @@ visit_schedule <- nv_neuro %>%
   ) %>%
   distinct()
 
-# Get subject characteristics with treatment information from adsl_neuro ----
+# Alpha Synuclein data generation
+
+# Get subject characteristics with treatment information from dm_neuro ----
 subject_chars <- dm_neuro %>%
-  select(STUDYID, USUBJID) %>%
-  left_join(
-    adsl_neuro %>% select(STUDYID, USUBJID, TRT01P, TRT01PN, TRTSDT),
-    by = c("STUDYID", "USUBJID")
-  ) %>%
-  mutate(
-    # Create treatment groups for analysis
+  select(STUDYID, USUBJID, ARM, ARMCD) %>%
+  mutate( # Create treatment groups for analysis (pattern as in nv_neuro.R)
     TRTGRP = case_when(
-      TRT01P %in% c("Placebo", "No Treatment") ~ "PLACEBO_CONTROL",
-      TRUE ~ "TREATMENT"
+      ARM == "Placebo" ~ "PLACEBO_CONTROL",
+      ARMCD == "Pbo" ~ "PLACEBO_CONTROL",
+      ARMCD == "Xan_Hi" ~ "TREATMENT",
+      is.na(ARMCD) ~ "PLACEBO_CONTROL"
     )
   )
 
-# Create LB record for one subject-visit ----
-create_lb_record <- function(usubjid, visitnum, visit, visitdy, lbdtc, lbdy, trtgrp) {
+# Create Alpha Synuclein Seed Amplification Assay record for one subject-visit ----
+create_asyn_record <- function(usubjid, visitnum, visit, visitdy, lbdtc, lbdy, trtgrp) {
   # Define positive rates based on treatment group and visit
   pos_rate <- case_when(
     trtgrp == "PLACEBO_CONTROL" ~ 0.30, # 30% positive for placebo/control at all visits
@@ -101,12 +104,12 @@ create_lb_record <- function(usubjid, visitnum, visit, visitdy, lbdtc, lbdy, trt
 # Set seed for reproducibility
 set.seed(2774)
 
-# Generate all LB records
-all_lb_records <- visit_schedule %>%
+# Generate Alpha Synuclein LB records
+asyn_records <- visit_schedule %>%
   left_join(subject_chars, by = c("USUBJID")) %>%
   rowwise() %>%
   do(
-    create_lb_record(
+    create_asyn_record(
       usubjid = .$USUBJID,
       visitnum = .$VISITNUM,
       visit = .$VISIT,
@@ -118,8 +121,194 @@ all_lb_records <- visit_schedule %>%
   ) %>%
   ungroup()
 
+# pTau, Amyloid, and Ratio data generation
+# Input amyloid data from admiralneuro.adapet - ensure the data is accurate
+visit_all <- tribble(
+  ~USUBJID, ~CRIT1FL, ~CRIT1, ~VISITNUM, ~VISIT, ~LBDTC, ~LBDY,
+  "01-701-1015", "N", "CENTILOID < 24.1", 0, "BASELINE", "2014-01-02", 1,
+  "01-701-1015", "N", "CENTILOID < 24.1", 12, "WEEK 12", "2014-03-26", 84,
+  "01-701-1015", "N", "CENTILOID < 24.1", 26, "WEEK 26", "2014-07-02", 182,
+  "01-701-1023", "N", "CENTILOID < 24.1", 0, "BASELINE", "2012-08-05", 1,
+  "01-701-1028", "N", "CENTILOID < 24.1", 0, "BASELINE", "2013-07-19", NA,
+  "01-701-1028", "N", "CENTILOID < 24.1", 12, "WEEK 12", "2013-10-09", NA,
+  "01-701-1028", "N", "CENTILOID < 24.1", 26, "WEEK 26", "2014-01-14", NA,
+  "01-701-1034", "N", "CENTILOID < 24.1", 0, "BASELINE", "2014-07-01", 1,
+  "01-701-1034", "N", "CENTILOID < 24.1", 12, "WEEK 12", "2014-09-25", 87,
+  "01-701-1034", "N", "CENTILOID < 24.1", 26, "WEEK 26", "2014-12-30", 183,
+  "01-701-1146", "N", "CENTILOID < 24.1", 0, "BASELINE", "2013-05-20", 1,
+  "01-701-1153", "N", "CENTILOID < 24.1", 0, "BASELINE", "2013-09-23", 1,
+  "01-701-1153", "N", "CENTILOID < 24.1", 12, "WEEK 12", "2013-12-16", 85,
+  "01-701-1153", "N", "CENTILOID < 24.1", 26, "WEEK 26", "2014-04-01", 191,
+  "01-701-1181", "N", "CENTILOID < 24.1", 0, "BASELINE", "2013-12-05", NA,
+  "01-701-1234", "N", "CENTILOID < 24.1", 0, "BASELINE", "2013-03-30", 1,
+  "01-701-1234", "N", "CENTILOID < 24.1", 12, "WEEK 12", "2013-07-07", 100,
+  "01-701-1234", "N", "CENTILOID < 24.1", 26, "WEEK 26", "2013-09-22", 177,
+  "01-701-1275", "N", "CENTILOID < 24.1", 0, "BASELINE", "2014-02-07", 1,
+  "01-701-1275", "N", "CENTILOID < 24.1", 12, "WEEK 12", "2014-05-03", 86,
+  "01-701-1302", "N", "CENTILOID < 24.1", 0, "BASELINE", "2013-08-29", 1,
+  "01-701-1302", "Y", "CENTILOID < 24.1", 12, "WEEK 12", "2013-11-05", 69,
+  "01-701-1345", "N", "CENTILOID < 24.1", 0, "BASELINE", "2013-10-08", NA,
+  "01-701-1345", "N", "CENTILOID < 24.1", 12, "WEEK 12", "2013-12-31", NA,
+  "01-701-1360", "N", "CENTILOID < 24.1", 0, "BASELINE", "2013-07-31", NA,
+  "01-701-1383", "N", "CENTILOID < 24.1", 0, "BASELINE", "2013-02-04", 1,
+  "01-701-1383", "N", "CENTILOID < 24.1", 12, "WEEK 12", "2013-04-30", 86,
+  "01-701-1383", "Y", "CENTILOID < 24.1", 26, "WEEK 26", "2013-08-06", 184,
+  "01-701-1392", "N", "CENTILOID < 24.1", 0, "BASELINE", "2012-10-28", 1,
+  "01-701-1392", "N", "CENTILOID < 24.1", 12, "WEEK 12", "2013-01-20", 85,
+  "01-701-1392", "N", "CENTILOID < 24.1", 26, "WEEK 26", "2013-04-28", 183,
+  "01-714-1288", "N", "CENTILOID < 24.1", 0, "BASELINE", "2013-12-04", NA,
+  "01-714-1288", "N", "CENTILOID < 24.1", 12, "WEEK 12", "2014-03-02", NA,
+  "01-714-1288", "N", "CENTILOID < 24.1", 26, "WEEK 26", "2014-06-17", NA
+)
+
+# Create LB record for one subject-visit with pTau, Amyloid, and Ratio ----
+create_ratio_record <- function(
+  usubjid,
+  visitnum,
+  visit,
+  visitdy,
+  lbdtc,
+  lbdy,
+  trtgrp,
+  crit1fl
+) {
+  set.seed(as.numeric(gsub("\\D", "", usubjid)) + visitnum)
+
+  # Generate Aβ42 plasma  ----
+  amyloid_value <- runif(1, 80, 1200) # pg/mL
+
+  # Generate pTau conditional on crit1fl status
+  ptau_value <- case_when(
+    crit1fl == "Y" ~ runif(1,
+      min = 0.0015 * amyloid_value,
+      max = 0.00370 * amyloid_value
+    ),
+    crit1fl == "N" ~ runif(1,
+      min = 0.00738 * amyloid_value,
+      max = 0.0120 * amyloid_value
+    ),
+    TRUE ~ runif(1,
+      min = 0.00371 * amyloid_value,
+      max = 0.00737 * amyloid_value
+    )
+  )
+
+  # Placebo / Untreated stability
+  if (trtgrp %in% c("Placebo", "No Treatment") && visit != "BASELINE") {
+    ptau_value <- ptau_value * runif(1, 0.98, 1.02)
+    amyloid_value <- amyloid_value * runif(1, 0.98, 1.02)
+  }
+
+  # add Intermediate cases
+  make_intermediate <- runif(1) < 0.15 # ~15% of visits
+
+  if (make_intermediate) {
+    # Force ratio into intermediate band
+    ratio_target <- runif(1, 0.00371, 0.00737)
+
+    # Adjust pTau (Aβ42 unchanged)
+    ptau_value <- ratio_target * amyloid_value
+  }
+
+  # Derive ratio
+  ratio_value <- ptau_value / amyloid_value
+
+  # Interpretation
+  ratio_lbnrind <- case_when(
+    ratio_value <= 0.00370 ~ "Negative",
+    ratio_value >= 0.00738 ~ "Positive",
+    TRUE ~ "Indeterminate"
+  )
+
+  # ---- pTau record ----
+  ptau_record <- tibble(
+    STUDYID   = "CDISCPILOT01",
+    DOMAIN    = "LB",
+    USUBJID   = usubjid,
+    LBTESTCD  = "PTAU217",
+    LBTEST    = "Lumipulse G pTau 217 Plasma",
+    LBCAT     = "Biomarkers",
+    LBORRES   = sprintf("%.4f", ptau_value),
+    LBORRESU  = "pg/mL",
+    LBSTRESC  = sprintf("%.4f", ptau_value),
+    LBSTRESN  = ptau_value,
+    LBSTRESU  = "pg/mL",
+    LBBLFL    = ifelse(visit == "BASELINE", "Y", NA_character_),
+    VISITNUM  = visitnum,
+    VISIT     = visit,
+    VISITDY   = visitdy,
+    LBDTC     = lbdtc,
+    LBDY      = lbdy
+  )
+
+  # ---- Aβ42 record ----
+  amyloid_record <- tibble(
+    STUDYID   = "CDISCPILOT01",
+    DOMAIN    = "LB",
+    USUBJID   = usubjid,
+    LBTESTCD  = "AMYLB42",
+    LBTEST    = "Lumipulse G Beta-Amyloid 1-42-N Plasma",
+    LBCAT     = "Biomarkers",
+    LBORRES   = sprintf("%.1f", amyloid_value),
+    LBORRESU  = "pg/mL",
+    LBSTRESC  = sprintf("%.1f", amyloid_value),
+    LBSTRESN  = amyloid_value,
+    LBSTRESU  = "pg/mL",
+    LBBLFL    = ifelse(visit == "BASELINE", "Y", NA_character_),
+    VISITNUM  = visitnum,
+    VISIT     = visit,
+    VISITDY   = visitdy,
+    LBDTC     = lbdtc,
+    LBDY      = lbdy
+  )
+
+  # ---- Ratio record ----
+  ratio_record <- tibble(
+    STUDYID   = "CDISCPILOT01",
+    DOMAIN    = "LB",
+    USUBJID   = usubjid,
+    LBTESTCD  = "PTAB42R",
+    LBTEST    = "Lumipulse G pTau 217/Beta-Amyloid 1-42 Plasma Ratio",
+    LBCAT     = "Biomarkers",
+    LBORRES   = sprintf("%.5f", ratio_value),
+    LBORNRLO  = "0.00370",
+    LBORNRHI  = "0.00738",
+    LBSTRESC  = sprintf("%.5f", ratio_value),
+    LBSTRESN  = ratio_value,
+    LBSTNRLO  = 0.00370,
+    LBSTNRHI  = 0.00738,
+    LBNRIND   = ratio_lbnrind,
+    LBBLFL    = ifelse(visit == "BASELINE", "Y", NA_character_),
+    VISITNUM  = visitnum,
+    VISIT     = visit,
+    VISITDY   = visitdy,
+    LBDTC     = lbdtc,
+    LBDY      = lbdy
+  )
+
+  bind_rows(ptau_record, amyloid_record, ratio_record)
+}
+
+# Generate all LB pTau, Amyloid and corresponding Ratio's records by joining 'visit_schedule' and 'subject_chars' ----
+ratio_records <- visit_all %>%
+  left_join(subject_chars, by = "USUBJID") %>%
+  rowwise() %>%
+  do(
+    create_ratio_record(
+      usubjid  = .$USUBJID,
+      visitnum = .$VISITNUM,
+      visit    = .$VISIT,
+      visitdy  = .$LBDY,
+      lbdtc    = .$LBDTC,
+      lbdy     = .$LBDY,
+      trtgrp   = .$TRTGRP,
+      crit1fl  = .$CRIT1FL
+    )
+  ) %>%
+  ungroup()
+
 # Add sequence numbers and finalize
-lb_neuro <- all_lb_records %>%
+lb_neuro <- bind_rows(asyn_records, ratio_records) %>%
   arrange(USUBJID, VISITNUM) %>%
   group_by(USUBJID) %>%
   mutate(LBSEQ = row_number()) %>%
@@ -132,14 +321,29 @@ lb_neuro <- all_lb_records %>%
   )
 
 # Validation checks
-expected_visits <- c("BASELINE")
-stopifnot(all(lb_neuro$VISIT %in% expected_visits))
-stopifnot(all(lb_neuro$LBORRES %in% c("Positive", "Negative")))
-stopifnot(all(nchar(lb_neuro$LBTESTCD) <= 8))
+expected_visits <- c("BASELINE", "WEEK 12", "WEEK 26")
+
+# Check if all VISIT values are in the expected set
+if (!all(lb_neuro$VISIT %in% expected_visits)) {
+  cli_abort("The values in 'lb_neuro$VISIT' are not all in the expected 'expected_visits'.")
+}
+
+# Check if LBORRES values are either "Positive" or "Negative"
+ASYNASAA_data <- lb_neuro[lb_neuro$LBTESTCD == "ASYNASAA", ]
+if (!all(ASYNASAA_data$LBORRES %in% c("Positive", "Negative"))) {
+  cli_abort(
+    message = "For LBTESTCD = ASYNASAA, the values in 'LBORRES' must be either 'Positive' or 'Negative'."
+  )
+}
+
+# Check if LBTESTCD values have more than 8 characters
+if (!all(nchar(lb_neuro$LBTESTCD) <= 8)) {
+  cli_abort("The length of values in 'lb_neuro$LBTESTCD' must not exceed 8 characters.")
+}
 
 # Check for one record per subject per visit
 visit_counts <- lb_neuro %>%
-  count(USUBJID, VISIT) %>%
+  count(USUBJID, LBTESTCD, VISIT) %>%
   filter(n > 1)
 
 if (nrow(visit_counts) > 0) {

data/lb_neuro.rda

@@ -2,6 +2,7 @@ ADCOEQ
 ADEG
 ADaM
 AE
+AMYLB
 ANISO
 AST
 ASYNASAA
@@ -73,6 +74,7 @@ ISTEST
 ISTESTCD
 Immunogenicity
 Intraocular
+JSON
 Kangjie
 Kumari
 LAMZ
@@ -86,6 +88,7 @@ LPERP
 LYM
 LYMLE
 Laterality
+Lumipulse
 MACROCY
 MCH
 MCHC
@@ -119,6 +122,8 @@ PPTEST
 PPTESTCD
 PROT
 PSA
+PTAB
+PTAU
 Pharmacokinetic
 Pharmaverse
 Phosphatase
@@ -136,6 +141,7 @@ RECIST
 RENALCL
 RSTEST
 RSTESTCD
+Recode
 Retinopathy
 Rohan
 SCTEST
@@ -213,6 +219,7 @@ funder
 iRECIST
 neuro
 onco
+pTau
 pharmaverse
 pre
 qs
@@ -221,3 +228,4 @@ savoury
 sdtm
 supprs
 yoghurts
+β