Merge pull request #146 from RConsortium/adadas_locf_update

FDA Feedback: Closes #152 Derive LOCF only considering ANL01FL=Y
RConsortium · Feb 13, 2024 · d2667c4 · d2667c4
2 parents 0092041 + 45a7e7b
commit d2667c4
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diff --git a/submission/adam/adadas.xpt b/submission/adam/adadas.xpt
diff --git a/submission/output/tlf-primary-pilot3.rtf b/submission/output/tlf-primary-pilot3.rtf
@@ -59,7 +59,7 @@
 {\f1\fs20\i [3] Pairwise comparison with treatment as a categorical variable: p-values without adjustment for multiple comparisons.}
 \par\ql\tx7245\tqr\tx12960
 {\f1\fs20\i Source: <run interactively>}\pmartabqr 
-{\f1\fs20\i 19:46 Friday, August 25, 2023}\par
+{\f1\fs20\i 18:17 Friday, February 09, 2024}\par
 }
 {
 \trowd
@@ -139,9 +139,9 @@
 \clbrdrt\clbrdrl\clbrdrb\clbrdrr\clvertalt\clpadfl0\clpadl120 \clpadft0\clpadt120 \clpadfb0\clpadb120 \clpadfr0\clpadr120 \cellx6740 
 \clbrdrt\clbrdrl\clbrdrb\clbrdrr\clvertalt\clpadfl0\clpadl120 \clpadft0\clpadt120 \clpadfb0\clpadb120 \clpadfr0\clpadr120 \cellx8986 
 \clbrdrt\clbrdrl\clbrdrb\clbrdrr\clvertalt\clpadfl0\clpadl120 \clpadft0\clpadt120 \clpadfb0\clpadb120 \clpadfr0\clpadr120 \cellx11232 \pard\intbl\ql{Mean (SD)}\cell
-\pard\intbl\ql{26.8 (13.78)}\cell
-\pard\intbl\ql{26.5 (13.30)}\cell
-\pard\intbl\ql{22.7 (12.54)}\cell
+\pard\intbl\ql{26.7 (13.79)}\cell
+\pard\intbl\ql{26.4 (13.18)}\cell
+\pard\intbl\ql{22.8 (12.48)}\cell
 \row
 }
 
@@ -187,9 +187,9 @@
 \clbrdrt\clbrdrl\clbrdrb\clbrdrr\clvertalt\clpadfl0\clpadl120 \clpadft0\clpadt120 \clpadfb0\clpadb120 \clpadfr0\clpadr120 \cellx6740 
 \clbrdrt\clbrdrl\clbrdrb\clbrdrr\clvertalt\clpadfl0\clpadl120 \clpadft0\clpadt120 \clpadfb0\clpadb120 \clpadfr0\clpadr120 \cellx8986 
 \clbrdrt\clbrdrl\clbrdrb\clbrdrr\clvertalt\clpadfl0\clpadl120 \clpadft0\clpadt120 \clpadfb0\clpadb120 \clpadfr0\clpadr120 \cellx11232 \pard\intbl\ql{Mean (SD)}\cell
-\pard\intbl\ql{ 2.6 ( 5.83)}\cell
-\pard\intbl\ql{ 2.0 ( 5.62)}\cell
-\pard\intbl\ql{ 1.4 ( 4.40)}\cell
+\pard\intbl\ql{ 2.5 ( 5.80)}\cell
+\pard\intbl\ql{ 2.0 ( 5.55)}\cell
+\pard\intbl\ql{ 1.5 ( 4.26)}\cell
 \row
 }
 
@@ -201,7 +201,7 @@
 \clbrdrt\clbrdrl\clbrdrb\clbrdrr\clvertalt\clpadfl0\clpadl120 \clpadft0\clpadt120 \clpadfb0\clpadb120 \clpadfr0\clpadr120 \cellx11232 \pard\intbl\ql{Median (Range)}\cell
 \pard\intbl\ql{ 2.0 (-11;16)}\cell
 \pard\intbl\ql{ 2.0 (-11;17)}\cell
-\pard\intbl\ql{ 1.0 ( -7;14)}\cell
+\pard\intbl\ql{ 1.0 ( -7;13)}\cell
 \row
 }
 
@@ -213,7 +213,7 @@
 \clbrdrt\clbrdrl\clbrdrb\clbrdrr\clvertalt\clpadfl0\clpadl120 \clpadft0\clpadt120 \clpadfb0\clpadb120 \clpadfr0\clpadr120 \cellx11232 \pard\intbl\ql{p-value(Dose Response) [1][2]}\cell
 \pard\intbl\ql{}\cell
 \pard\intbl\ql{}\cell
-\pard\intbl\ql{   0.187    }\cell
+\pard\intbl\ql{   0.245    }\cell
 \row
 }
 
@@ -236,8 +236,8 @@
 \clbrdrt\clbrdrl\clbrdrb\clbrdrr\clvertalt\clpadfl0\clpadl120 \clpadft0\clpadt120 \clpadfb0\clpadb120 \clpadfr0\clpadr120 \cellx8986 
 \clbrdrt\clbrdrl\clbrdrb\clbrdrr\clvertalt\clpadfl0\clpadl120 \clpadft0\clpadt120 \clpadfb0\clpadb120 \clpadfr0\clpadr120 \cellx11232 \pard\intbl\ql{p-value(Xan - Placebo) [1][3]}\cell
 \pard\intbl\ql{}\cell
-\pard\intbl\ql{   0.534    }\cell
-\pard\intbl\ql{   0.173    }\cell
+\pard\intbl\ql{   0.569    }\cell
+\pard\intbl\ql{   0.233    }\cell
 \row
 }
 
@@ -248,8 +248,8 @@
 \clbrdrt\clbrdrl\clbrdrb\clbrdrr\clvertalt\clpadfl0\clpadl120 \clpadft0\clpadt120 \clpadfb0\clpadb120 \clpadfr0\clpadr120 \cellx8986 
 \clbrdrt\clbrdrl\clbrdrb\clbrdrr\clvertalt\clpadfl0\clpadl120 \clpadft0\clpadt120 \clpadfb0\clpadb120 \clpadfr0\clpadr120 \cellx11232 \pard\intbl\ql{  Diff of LS Means (SE)}\cell
 \pard\intbl\ql{}\cell
-\pard\intbl\ql{-0.5 (0.83)}\cell
-\pard\intbl\ql{-1.2 (0.86)}\cell
+\pard\intbl\ql{-0.5 (0.82)}\cell
+\pard\intbl\ql{-1.0 (0.84)}\cell
 \row
 }
 
@@ -260,8 +260,8 @@
 \clbrdrt\clbrdrl\clbrdrb\clbrdrr\clvertalt\clpadfl0\clpadl120 \clpadft0\clpadt120 \clpadfb0\clpadb120 \clpadfr0\clpadr120 \cellx8986 
 \clbrdrt\clbrdrl\clbrdrb\clbrdrr\clvertalt\clpadfl0\clpadl120 \clpadft0\clpadt120 \clpadfb0\clpadb120 \clpadfr0\clpadr120 \cellx11232 \pard\intbl\ql{  95% CI}\cell
 \pard\intbl\ql{}\cell
-\pard\intbl\ql{(-2.2;1.1)}\cell
-\pard\intbl\ql{(-2.9;0.5)}\cell
+\pard\intbl\ql{(-2.1;1.1)}\cell
+\pard\intbl\ql{(-2.7;0.7)}\cell
 \row
 }
 
@@ -285,7 +285,7 @@
 \clbrdrt\clbrdrl\clbrdrb\clbrdrr\clvertalt\clpadfl0\clpadl120 \clpadft0\clpadt120 \clpadfb0\clpadb120 \clpadfr0\clpadr120 \cellx11232 \pard\intbl\ql{p-value(Xan High - Xan Low) [1][3]}\cell
 \pard\intbl\ql{}\cell
 \pard\intbl\ql{}\cell
-\pard\intbl\ql{   0.446    }\cell
+\pard\intbl\ql{   0.520    }\cell
 \row
 }
 
@@ -297,7 +297,7 @@
 \clbrdrt\clbrdrl\clbrdrb\clbrdrr\clvertalt\clpadfl0\clpadl120 \clpadft0\clpadt120 \clpadfb0\clpadb120 \clpadfr0\clpadr120 \cellx11232 \pard\intbl\ql{  Diff of LS Means (SE)}\cell
 \pard\intbl\ql{}\cell
 \pard\intbl\ql{}\cell
-\pard\intbl\ql{-0.6 (0.85)}\cell
+\pard\intbl\ql{-0.5 (0.84)}\cell
 \row
 }
 
@@ -309,7 +309,7 @@
 \clbrdrt\clbrdrl\clbrdrb\clbrdrr\clvertalt\clpadfl0\clpadl120 \clpadft0\clpadt120 \clpadfb0\clpadb120 \clpadfr0\clpadr120 \cellx11232 \pard\intbl\ql{  95% CI}\cell
 \pard\intbl\ql{}\cell
 \pard\intbl\ql{}\cell
-\pard\intbl\ql{(-2.3;1.0)}\cell
+\pard\intbl\ql{(-2.2;1.1)}\cell
 \row
 }
 

diff --git a/submission/pkgs4adrg.r b/submission/pkgs4adrg.r
@@ -6,15 +6,15 @@ library(data.table)
 pkgloaded <- sessionInfo()$loadedOnly #get intial list of packages that were loaded
 pkgother <- sessionInfo()$otherPkgs #get initla list of packages that were also listed in the Session but may not have been used
 
-loaded <- data.frame(rbindlist(pkgloaded, idcol = TRUE, fill=T)) %>% 
-            select(Package, Title, Version, Description) %>% 
-            mutate(loaded='Y')
-other <- data.frame(rbindlist(pkgother, idcol = TRUE, fill=T)) %>% 
-            select(Package, Title, Version, Description) %>% 
-            mutate(loaded='N')
+loaded <- data.frame(rbindlist(pkgloaded, idcol = TRUE, fill = TRUE)) %>%
+            select(Package, Title, Version, Description) %>%
+            mutate(loaded = "Y")
+other <- data.frame(rbindlist(pkgother, idcol = TRUE, fill = TRUE)) %>%
+            select(Package, Title, Version, Description) %>%
+            mutate(loaded = "N")
 
 pkgdesc <- bind_rows(loaded, other) # stacks all package data frames.
 # NOTE column 'loaded', from this data frame can be used to subset out packages not used and may not be needed for the adrg.pdf
 
-# update path to save CSV in your local area.  
-write.csv(pkgdesc, "/cloud/project/submission/pkgs4adrg.csv", row.names=FALSE)
+# update path to save CSV in your local area.
+write.csv(pkgdesc, "/cloud/project/submission/pkgs4adrg.csv", row.names = FALSE)
diff --git a/submission/programs/adadas.r b/submission/programs/adadas.r
@@ -80,27 +80,6 @@ adas2 <- adas1 %>%
   create_var_from_codelist(adadas_spec, AVISIT, AVISITN) %>% # derive AVISITN from codelist
   create_var_from_codelist(adadas_spec, PARAM, PARAMN) # derive PARAMN from codelist
 
-# derive PARAMCD=ACTOT, DTYPE=LOCF
-# A dataset with combinations of PARAMCD, AVISIT which are expected.
-actot_expected_obsv <- tibble::tribble(
-  ~PARAMCD, ~AVISITN, ~AVISIT,
-  "ACTOT", 0, "Baseline",
-  "ACTOT", 8, "Week 8",
-  "ACTOT", 16, "Week 16",
-  "ACTOT", 24, "Week 24"
-)
-
-adas_locf <- derive_locf_records(
-  data = adas2,
-  dataset_expected_obs = actot_expected_obsv,
-  by_vars = exprs(
-    STUDYID, SITEID, SITEGR1, USUBJID, TRTSDT, TRTEDT,
-    TRTP, TRTPN, AGE, AGEGR1, AGEGR1N, RACE, RACEN, SEX,
-    ITTFL, EFFFL, COMP24FL, PARAMCD
-  ),
-  order = exprs(AVISITN, AVISIT),
-  keep_vars = exprs(VISIT, VISITNUM, ADY, ADT, PARAM, PARAMN, QSSEQ)
-)
 
 ## derive AWRANGE/AWTARGET/AWTDIFF/AWLO/AWHI/AWU
 aw_lookup <- tribble(
@@ -112,7 +91,7 @@ aw_lookup <- tribble(
 )
 
 adas3 <- derive_vars_merged(
-  adas_locf,
+  adas2,
   dataset_add = aw_lookup,
   by_vars = exprs(AVISIT)
 ) %>%
@@ -122,8 +101,60 @@ adas3 <- derive_vars_merged(
   )
 
 
-## baseline information BASE/CHG/PCHG
+## ANL01FL
 adas4 <- adas3 %>%
+  mutate(diff = AWTARGET - ADY) %>%
+  restrict_derivation(
+    derivation = derive_var_extreme_flag,
+    args = params(
+      by_vars = exprs(USUBJID, PARAMCD, AVISIT),
+      order = exprs(AWTDIFF, diff),
+      new_var = ANL01FL,
+      mode = "first"
+    ),
+    filter = !is.na(AVISIT)
+  )
+
+# derive PARAMCD=ACTOT, DTYPE=LOCF
+# A dataset with combinations of PARAMCD, AVISIT which are expected.
+actot_expected_obsv <- tibble::tribble(
+  ~PARAMCD, ~AVISITN, ~AVISIT,
+  "ACTOT", 0, "Baseline",
+  "ACTOT", 8, "Week 8",
+  "ACTOT", 16, "Week 16",
+  "ACTOT", 24, "Week 24"
+)
+
+adas_locf2 <- adas4 %>%
+  restrict_derivation(
+    derivation = derive_locf_records,
+    args = params(
+      dataset_expected_obs = actot_expected_obsv,
+      by_vars = exprs(
+        STUDYID, SITEID, SITEGR1, USUBJID, TRTSDT, TRTEDT,
+        TRTP, TRTPN, AGE, AGEGR1, AGEGR1N, RACE, RACEN, SEX,
+        ITTFL, EFFFL, COMP24FL, PARAMCD
+      ),
+      order = exprs(AVISITN, AVISIT),
+      keep_vars = exprs(VISIT, VISITNUM, ADY, ADT, PARAM, PARAMN, QSSEQ)
+    ),
+    filter = !is.na(ANL01FL)
+  ) %>%
+  ################# assign ANL01FL for new records
+  mutate(ANL01FL = if_else(is.na(DTYPE), ANL01FL, "Y")) %>%
+  ################# re-derive AWRANGE/AWTARGET/AWTDIFF/AWLO/AWHI/AWU
+  select(-c("AWRANGE", "AWTARGET", "AWLO", "AWHI")) %>%
+  derive_vars_merged(
+    dataset_add = aw_lookup,
+    by_vars = exprs(AVISIT)
+  ) %>%
+  mutate(
+    AWTDIFF = abs(AWTARGET - ADY),
+    AWU = "DAYS"
+  )
+
+## baseline information BASE/CHG/PCHG
+adas5 <- adas_locf2 %>%
   # Calculate BASE
   derive_var_base(
     by_vars = exprs(STUDYID, USUBJID, PARAMCD),
@@ -141,19 +172,7 @@ adas4 <- adas3 %>%
     filter = is.na(ABLFL)
   )
 
-## ANL01FL
-adas5 <- adas4 %>%
-  mutate(diff = AWTARGET - ADY) %>%
-  restrict_derivation(
-    derivation = derive_var_extreme_flag,
-    args = params(
-      by_vars = exprs(USUBJID, PARAMCD, AVISIT),
-      order = exprs(AWTDIFF, diff),
-      new_var = ANL01FL,
-      mode = "first"
-    ),
-    filter = !is.na(AVISIT)
-  )
+
 
 ## out to XPT
 adas5 %>%