Bug: AUC start 0 (which also needs Feature: C0 imputation) #138

Gero1999 · 2024-11-27T14:27:45Z

Issue

Closes #2 #60

Description

After running NCA, AUC calculations always consider the discrete start (start at where first concentration sample was collected). This can indeed alter slightly the real values of the AUC. This is a consequence of 2 problems:

Doses times are being considered at the first measure, instead of at the real dose time
No imputed measure at dose time is consdiered

Change description.

Definition of Done

C0 imputation option for the user specified in Setup > Data Selection

How to test

At "NCA">"NCA Results", when C0 is imputed it is expected that start=AFRLT-ARRLT (being AFRLT-ARRLT= 0 in DOSNO=1)
At "NCA">"NCA Results", when C0 is not imputed it is expected that start={time of 1st observation}
AUC values (auclast, aucinf...) from start=AFRLT-ARRLT are calculated when C0 is imputed
All variables that should only be based on observed data (cmax, tmax...) are not considering C0 imputations
Test that PKNCA also deals well with predoses as duplicates for the NCA
Check slope selector plots and NCA results remain well after running NCA
Check if in general C0 imputation logic works well (NCA experts):
if C0 exists ~ C0=C0
if DOSNO=1 & IV bolus (ADOSEDUR=0, ROUTE=intravascular) ~ C0=0
if DOSNO>1 & not IV bolus ~ C0=predose
if IV bolus and monoexponential data ~ logslope
if IV bolus and not monoexponential data ~ C0=C1

Contributor checklist

Code passes lintr checks
Code passes all unit tests
New logic covered by unit tests
New logic is documented

Notes to reviewer

Anything that the reviewer should know before tacking the pull request?

…rt for non-c0 parameters

…ute_predose

…tion

…d renamed (select_X)

…adjust reshape for it

Merge remote-tracking branch 'origin/main' into bug/auc-start-0 # Conflicts: # inst/shiny/tabs/nca.R # inst/shiny/tabs/outputs.R

Merge branch 'bug/auc-start-0' of https://github.com/pharmaverse/aNCA into bug/auc-start-0 # Conflicts: # R/create_start_impute.R

…mentation

…to slice data. route_column (unneeded argument) was removed

…into bug/auc-start-0

Gero1999 · 2025-01-15T08:24:07Z

Thanks for your reviews and feedback, I hope that now all looks fine! @js3110 @m-kolomanski

m-kolomanski

Hey, looks much better, thank you for all the hard work! I still do have some feedback, most of it regards style and consistency rather thank quality of the code, but also there seems like some of my comments from the previous review were not addressed?

R/PKNCA_impute_method_additions.R

R/create_start_impute.R

inst/shiny/tabs/nca.R

inst/shiny/ui.R

m-kolomanski · 2025-01-15T11:56:46Z

tests/testthat/test-format_data.R

issue: For all the test files, please utilize describe and it when writing tests, you can check test-general_lineplot.R, test-utils-slope_selector.R or test-utils.R for good examples. Also this blogpost might be useful to better explain the idea behind it.

m-kolomanski · 2025-01-15T13:09:49Z

R/create_start_impute.R

+    mutate(
+      impute = case_when(
+        !!sym(time_column) == start & !is.na(!!sym(conc_column)) ~ NA,
+        DOSNO == 1 &
+          (tolower(!!sym(route_column)) == "extravascular" |
+             !!sym(duration_column) > 0 |
+             !!sym(analyte_column) != !!sym(drug_column)) ~ "start_conc0",
+        DOSNO > 1 &
+          (tolower(!!sym(route_column)) == "extravascular" |
+             !!sym(duration_column) > 0 |
+             !!sym(analyte_column) != !!sym(drug_column)) ~ "start_predose",
+        tolower(!!sym(route_column)) == "intravascular" &
+          !!sym(duration_column) == 0 &
+          !!sym(analyte_column) == !!sym(drug_column) &
+          is.possible.c0.logslope ~ "start_logslope",
+        tolower(!!sym(route_column)) == "intravascular" &
+          !!sym(duration_column) == 0 &
+          !!sym(analyte_column) == !!sym(drug_column) ~ "start_c1"
+      )
+    ) %>%


issue: this comment seems to not have been resolved at all? It is still quite hard to decipher what exactly we are checking here.

js3110 · 2025-01-15T14:55:01Z

@Gero1999 it looks good and thank you for all the hard work on this! Unfortunately I have noticed a couple of things:

In the data selection, after you select analyte and dose number, the table shown does not represent the selections, as I can still see all the dose numbers. We want this table for the user to see exactly the data that will be used for NCA, so either we need to filter the dose number here, or move the dose number selectInput. I will let you decide.
For the dummy data, Doseno >3 does not work and the app crashes. I get the following error: Error in if: argument is of length zero. I double checked and I do not get this issue in main, so it is related to something in this branch. Also, for DOSNO = 2, USUBJID 11102 has empty cells for lambda z calculation, but no explanation why and because of this the slope selection crashes. This could be created as a separate bug issue to fix later or you can see if its something to fix now.

Let me know if you have any questions or want any support :)

Co-authored-by: Mateusz Kołomański <[email protected]>

…start_impute

Co-authored-by: Mateusz Kołomański <[email protected]>

…table

m-kolomanski

From my side, looks good! Thank you for all the hard work, this is a lengthy change, sure it was not easy!

I am approving, but before merge, please remove the inst/WORDLIST.txt file, as it is redundant - the spelllcheck only uses WORDLIST file.

m-kolomanski · 2025-01-17T06:38:21Z

R/PKNCA_impute_method_additions.R

+    all_concs <- conc[time >= start  &  time <= end]
+    all_times <- time[time >= start  &  time <= end]


nitpick, style:

Suggested change

all_concs <- conc[time >= start & time <= end]

all_times <- time[time >= start & time <= end]

all_concs <- conc[time >= start & time <= end]

all_times <- time[time >= start & time <= end]

m-kolomanski · 2025-01-17T06:39:19Z

R/create_start_impute.R

+      impute = case_when(
+        # Start concentration already present: No imputation (NA)
+        !!sym(time_column) == start & !is.na(!!sym(conc_column)) ~ NA,
+
+        # 1st dose with not IV bolus or analyte =! drug : Start concentration is 0
+        is.first.dose & (!is.ivbolus | !is.analyte.drug) ~ "start_conc0",
+
+        # Posterior doses not IV bolus or analyte =! drug : Start concentration shifts to predose
+        !is.first.dose & (!is.ivbolus | !is.analyte.drug) ~ "start_predose",
+
+        # IV bolus with analyte = drug : Start concentration is log-backextrapolated (if possible)
+        is.ivbolus & is.analyte.drug & is.possible.c0.logslope ~ "start_logslope",
+
+        # IV bolus with analyte = drug and not possible logslope: Start concentration is 1st conc
+        is.ivbolus & is.analyte.drug ~ "start_c1"


Nice, looks clean, thank you for additional comments with explanations!

m-kolomanski · 2025-01-17T06:43:57Z

inst/WORDLIST.txt

issue(non-blocking): Please remove this file, it is redundant.

js3110

LGTM !!

Gero1999 added 26 commits November 5, 2024 09:26

bug: force doses times to be AFRLT.dose (at ARRLT = 0)

0d68014

data: correct PKROUTE -> ROUTE

b8cd1ea

enhancement: create function to create impute_c0 column

1aef135

enhancement: include additional C0 imputation strategies

ec3e109

feature: intervals include imputate strategy with duplicated rows apa…

50fb2e1

…rt for non-c0 parameters

bug: PKNCAconc formula adapted for PKNCA to consider predoses for imp…

82521f5

…ute_predose

bug: solved classification of doses in create_c0_impute

135152d

bug: perfectionated formulas to consider different analytes appropiately

18f4ee2

style: solve most lintr issues

7e93a4f

refactor: delete report files that should not have been called

0a5ba6d

refactor: nolint in customized PKNCA_impute_method functions

7dbfd74

wordlist: add PKNCA_impute_method functions

43d9f9e

documentation: functions in R/PKNCA_impute_method_additions.R

429a1e6

feature: c0 input & when no checked use as interval start 1st observa…

cb1ee9c

…tion

bug: solved PKNCA warnings "No concentration data"

86102f1

bug: solved issue of duplicated tmax in results

45e1e52

refactor: NCA results with all dose and conc columns first

2bab21b

bug: fixed impute_method_start_c1 unneded argument issue

a622e61

refactor: delete unused functions in reshape

c345c9b

refactor: input selectors for analyte and dosno put together in UI an…

769b80d

…d renamed (select_X)

refactor: change strategy for input of AUC intervals

79d4da4

bug: fixed new intervals strategy and align with PKNCA running

768b972

revert feat: back to old UI function for AUC intervals

bf8844b

fix: interval default start since dose, aucint for manual intervals, …

4411231

…adjust reshape for it

fix: when C0 is not imputed, start is at C1

5c5be0a

lintr: code cleaning

e211bd7

Gero1999 marked this pull request as draft November 28, 2024 09:37

Gero1999 added 3 commits November 28, 2024 11:24

fix: merge and solve nca.R/outputs.R conflicts

4f99610

Merge remote-tracking branch 'origin/main' into bug/auc-start-0 # Conflicts: # inst/shiny/tabs/nca.R # inst/shiny/tabs/outputs.R

fix: issue in slope_selector with new name for input$cyclenca

06fca2f

refactor: make own function to create intervals with dose data

a6bddfc

Gero1999 and others added 8 commits January 13, 2025 17:30

nitpick: solve m-kolomanski nitpicks

24c2ff0

Merge branch 'bug/auc-start-0' of https://github.com/pharmaverse/aNCA into bug/auc-start-0 # Conflicts: # R/create_start_impute.R

refactor: rename reshape_PKNCA_results to pivot_wider_pknca_results

cb43585

refactor: change the names of format_data.R functions and update docu…

fb31b67

…mentation

Merge branch 'main' into bug/auc-start-0

93d7432

fix: format_pkncadose_data includes either DOSNO or TIME (dose time) …

b8bd50c

…to slice data. route_column (unneeded argument) was removed

refactor: lintr cleaning and roxygen2 documentation update

9022603

Merge branch 'bug/auc-start-0' of https://github.com/pharmaverse/aNCA …

b204bc7

…into bug/auc-start-0

spelling: update wordlist

269a92c

Gero1999 requested review from js3110 and m-kolomanski January 15, 2025 08:20

m-kolomanski requested changes Jan 15, 2025

View reviewed changes

Gero1999 and others added 4 commits January 15, 2025 16:12

suggestions: nitpicks, returns m-kolomanski

9f81db4

Co-authored-by: Mateusz Kołomański <[email protected]>

refactor: clarify with logical columns create_start_impute.R assignation

036158b

issue: eliminate all redundant dplyr/tidyr namespacing

529a27d

issue: change base function to dplyr (base::merge > dplyr::inner_join)

25baba6

Gero1999 mentioned this pull request Jan 16, 2025

Bug: NCA intervals are based on actual cycles (DOSNO) or standard TAU, not on nominal ones #161

Open

Gero1999 and others added 2 commits January 16, 2025 15:40

fix: use describe/it in tests PKNCA_impute_method_additions & create_…

3032a3f

…start_impute

nitpick, suggestion: nca.R add backlash and de-namespace mutate

a5ea310

Co-authored-by: Mateusz Kołomański <[email protected]>

Gero1999 mentioned this pull request Jan 16, 2025

Enhancement: Delete Data Selection and move to Settings #162

Open

Gero1999 added 4 commits January 16, 2025 16:16

fix: filtering of dosno/analyte in displayed in Data Selection tab …

d87f10b

…table

fix: crash on slope_selector due to filtering results with NA lambda.z

93677f2

style: lintr clean code

8703c07

style: lintr code cleaning

c87ebb0

Gero1999 requested a review from m-kolomanski January 16, 2025 16:48

m-kolomanski approved these changes Jan 17, 2025

View reviewed changes

fix: remove redundant inst/WORDLIST.txt

2c9c1f4

js3110 approved these changes Jan 17, 2025

View reviewed changes

Gero1999 merged commit 64dc3dc into main Jan 17, 2025
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Bug: AUC start 0 (which also needs Feature: C0 imputation) #138

Bug: AUC start 0 (which also needs Feature: C0 imputation) #138

Gero1999 commented Nov 27, 2024 •

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		all_concs <- conc[time >= start & time <= end]
		all_times <- time[time >= start & time <= end]

Bug: AUC start 0 (which also needs Feature: C0 imputation) #138

Bug: AUC start 0 (which also needs Feature: C0 imputation) #138

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Gero1999 commented Nov 27, 2024 • edited Loading

Issue

Description

Definition of Done

How to test

Contributor checklist

Notes to reviewer

Gero1999 commented Jan 15, 2025

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Gero1999 commented Nov 27, 2024 •

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