Update adal01

book/listings/pharmacokinetic/adal01.qmd

@@ -22,81 +22,100 @@ adab <- synthetic_cdisc_dataset("latest", "adab")
 
 trt <- "A: Drug X"
 min_titer_ada <- 1.10
-min_titer_nab <- 0
-min_conc <- 0
+min_titer_nab <- 1.10
+min_conc <- 3.0
 
+if (unique(adpc$RELTMU) == "hr") adpc$NFRLT <- adpc$NFRLT / 24
 adpc_f <- adpc %>% filter(PARAM == "Plasma Drug X")
 
-if (unique(adab$RELTMU) == "day") adab$NFRLT <- adab$NFRLT * 24
 
 drug_a <- unique(adab$PARCAT1)[1]
 drugcd <- unique(adab$PARAMCD[adab$PARAM == "Antibody titer units"])[1]
-conc_u <- unique(adab$AVALU[adab$PARAM == "Antibody titer units"])[1]
+conc_u <- unique(adpc_f$AVALU)
 
 adpc_f <- adpc_f %>% select(USUBJID, NFRLT, AVAL)
-adab_f <- adab %>%
+adab1 <- adab %>%
   filter(ARM == trt) %>%
-  select(-PARAMCD, -PARCAT1, -AVALC, -AVALU) %>%
+  select(-PARAM, -PARCAT1, -AVALC, -AVALU) %>%
   left_join(
     adpc_f,
     by = c("USUBJID", "NFRLT"),
     suffix = c("_ab", "_pk")
   ) %>%
   filter(!is.na(AVAL_ab))
 
-adab_f <- adab_f %>%
+adab_f <- adab1 %>%
   tidyr::pivot_wider(
-    names_from = PARAM,
+    id_cols = c(USUBJID, VISIT, NFRLT, ISTPT, AVAL_pk),
+    names_from = PARAMCD,
     values_from = AVAL_ab
-  ) %>%
-  rename(
-    RES_ADA = `ADA interpreted per sample result`,
-    # TES_ADA = `Treatment Emergent - Positive`,
-    TU_ADA = `Antibody titer units`,
-    RES_NAB = `NAB interpreted per sample result`,
-    # TES_NAB = `Treatment Emergent - Positive, Neutralizing Antibody`,
-    TU_NAB = `Neutralizing Antibody titer units`
-  )
-
-out <- adab_f %>%
+  ) 
+# Select the necessary ADA parameters
+adab_f1 <- adab_f %>% 
+  select(USUBJID, VISIT, NFRLT, ISTPT, AVAL_pk, R1800000, R1800001, RESULT1, RESULT2, ADASTAT1, ADASTAT2) %>% 
+  mutate(ADA = R1800000, NAB = R1800001) %>% select(-R1800000, -R1800001)
+
+# %>%
+#   rename(
+#     RES_ADA = `ADA interpreted per sample result`,
+#     TES_ADA = `Treatment Emergent - Positive`,
+#     TU_ADA = `Antibody titer units`,
+#     RES_NAB = `NAB interpreted per sample result`,
+#     TES_NAB = `Treatment Emergent - Positive, Neutralizing Antibody`,
+#     TU_NAB = `Neutralizing Antibody titer units`
+#   )
+
+# Find subject level ADA status
+adab_s <- adab_f1 %>% select(USUBJID, ADASTAT1, ADASTAT2) %>% filter(!is.na(ADASTAT1), !is.na(ADASTAT2))
+# Find time-vary ADA records
+adab_r <- adab_f1 %>% select(-ADASTAT1, -ADASTAT2) %>% filter(!is.na(VISIT))
+
+adab_o <- adab_r %>% left_join(adab_s, by = "USUBJID")
+
+out <- adab_o %>%
   mutate(AVAL_pk = ifelse(AVAL_pk == 0, NA, AVAL_pk)) %>%
-  mutate_at(
-    c("NFRLT", "TU_ADA", "TU_NAB", "AVAL_pk"),
-    ~ ifelse(is.na(.), replace(., is.na(.), "N/A"), format(round(., 2), nsmall = 2))
-  ) %>%
   mutate(NFRLT = as.numeric(NFRLT)) %>%
   mutate(
-    RES_ADA = ifelse(RES_ADA == 1, "Positive", "Negative"),
-    # TES_ADA = ifelse(TES_ADA == 1, "Positive", "Negative"),
-    RES_NAB = ifelse(RES_NAB == 1, "Positive", "Negative"),
-    # TES_NAB = ifelse(TES_NAB == 1, "Positive", "Negative"),
-    TU_ADA = ifelse(TU_ADA <= min_titer_ada, "BLQ", TU_ADA),
-    TU_NAB = ifelse(TU_NAB <= min_titer_nab, "BLQ", TU_NAB),
-    AVAL_pk = ifelse(AVAL_pk <= min_conc, "BLQ", AVAL_pk)
+    RESULT1 = ifelse(RESULT1 == 1, "Positive", "Negative"),
+    RESULT2 = ifelse(RESULT2 == 1, "Positive", "Negative"),
+    ADASTAT1 = ifelse(ADASTAT1 == 1, "Positive", "Negative"),
+    ADASTAT2 = ifelse(ADASTAT2 == 1, "Positive", "Negative")
+    ,
+    # ADA = ifelse(ADA < min_titer_ada, NA, ADA), 
+    # NAB = ifelse(NAB < min_titer_nab, NA, NAB),
+    AVAL_pk = ifelse(AVAL_pk < min_conc, "BLQ", AVAL_pk)
   ) %>%
   select(
-    USUBJID, VISIT, ISTPT, NFRLT, RES_ADA, TU_ADA, # TES_ADA,
-    RES_NAB, TU_NAB, # TES_NAB,
+    USUBJID, VISIT, ISTPT, NFRLT, ADA, NAB, RESULT1, RESULT2, ADASTAT1, ADASTAT2,
     AVAL_pk
+  ) %>% 
+  mutate_at(
+    c("NFRLT", "ADA", "NAB", "AVAL_pk"),
+    ~ ifelse(is.na(.), replace(., is.na(.), "N/A"), format(round(., 2), nsmall = 2))
   )
 
 var_labels(out) <- names(out)
 
 out <- out %>%
+  arrange(USUBJID, VISIT, desc(ISTPT), NFRLT) %>% 
+  group_by(USUBJID) %>% 
+  mutate(ADASTAT1 = ifelse(row_number() == 1, ADASTAT1, ""),
+         ADASTAT2 = ifelse(row_number() == 1, ADASTAT2, "")) %>%    # Keep only the first value in ADA status, set others to ""
   var_relabel(
     USUBJID = "Subject ID",
     VISIT = "Visit",
     ISTPT = "Timepoint",
     NFRLT = "Nominal\nTime\n(hr)",
-    RES_ADA = "Sample\nADA\nResult",
-    TU_ADA = "ADA\nTiter\nUnits\n(1)",
-    # TES_ADA = "Patient\nTreatment\nEmergent ADA\nStatus",
-    RES_NAB = "Sample\nNeutralizing\nAntibody\n(NAb) Result",
-    TU_NAB = "NAb\nTiter\nUnits\n(2)",
-    # TES_NAB = "Patient\nTreatment\nEmergent NAb\nStatus",
+    RESULT1 = "Sample\nADA\nResult",
+    ADA = "ADA\nTiter\nUnits\n(1)",
+    ADASTAT1 = "Patient\nTreatment\nEmergent ADA\nStatus",
+    RESULT2 = "Sample\nNeutralizing\nAntibody\n(NAb) Result",
+    NAB = "NAb\nTiter\nUnits\n(2)",
+    ADASTAT2 = "Patient\nTreatment\nEmergent NAb\nStatus",
     AVAL_pk = paste0("Drug\nConcentration\n(", conc_u, ") (3)")
-  ) %>%
-  arrange(USUBJID, VISIT, desc(ISTPT), NFRLT)
+  )
+
+
 ```
 
 ## Standard Listing
@@ -112,8 +131,8 @@ lsting <- as_listing(
   ),
   subtitles = paste("\nTreatment Group:", trt),
   main_footer = "(1) Minimum reportable titer = 1.10 (example only)
-(2) Minimum reportable titer = 0 (example only)
-(3) Minimum reportable concentration = 0 (example only)
+(2) Minimum reportable titer = 1.10 (example only)
+(3) Minimum reportable concentration = 3.0 (example only)
 BLQ = Below Limit of Quantitation, LTR = Lower than Reportable, N/A = Not Applicable, N.C. = Not Calculable,
 ADA = Anti-Drug Antibodies (is also referred to as ATA, or Anti-Therapeutic Antibodies)
 ROXXXXXXX is also known as [drug]"