From 8f5210f958e17aee92aaf5015ecb6264699ff0a4 Mon Sep 17 00:00:00 2001 From: Vinh Nguyen Date: Wed, 8 Nov 2023 19:52:07 -0500 Subject: [PATCH 01/14] 233 - iRecist vignette initial draft --- _pkgdown.yml | 2 + vignettes/irecist.Rmd | 858 ++++++++++++++++++++++++++++++++++++++++++ 2 files changed, 860 insertions(+) create mode 100644 vignettes/irecist.Rmd diff --git a/_pkgdown.yml b/_pkgdown.yml index 5d3c9368..022243fb 100644 --- a/_pkgdown.yml +++ b/_pkgdown.yml @@ -77,3 +77,5 @@ navbar: href: articles/adtr.html - text: Creating and Using New Anti-Cancer Start Date href: articles/nactdt.html + - text: Creating ADRS with iRECIST endpoints + href: articles/irecist.html diff --git a/vignettes/irecist.Rmd b/vignettes/irecist.Rmd new file mode 100644 index 00000000..77968cf5 --- /dev/null +++ b/vignettes/irecist.Rmd @@ -0,0 +1,858 @@ +--- +title: "Creating ADRS with iRECIST endpoints" +output: + rmarkdown::html_vignette +vignette: > + %\VignetteIndexEntry{Creating ADRS with iRECIST endpoints} + %\VignetteEncoding{UTF-8} + %\VignetteEngine{knitr::rmarkdown} +--- + +```{r setup, include = FALSE} +knitr::opts_chunk$set( + collapse = TRUE, + comment = "#>" +) + +library(admiral) + +link <- function(text, url) { + return( + paste0( + "[", text, "]", + "(", url, ")" + ) + ) +} +dyn_link <- function(text, + base_url, + relative_url = "", + # Change to TRUE when admiral adopts multiversion docs + is_multiversion = FALSE, + multiversion_default_ref = "main") { + url <- paste(base_url, relative_url, sep = "/") + if (is_multiversion) { + url <- paste( + base_url, + Sys.getenv("BRANCH_NAME", multiversion_default_ref), + relative_url, + sep = "/" + ) + } + return(link(text, url)) +} +# Other variables +admiral_homepage <- "https://pharmaverse.github.io/admiral/cran-release" + +library(admiraldev) +``` + +# Introduction + +This article describes creating an `ADRS` ADaM with oncology endpoint parameters +based on iRECIST. It shows a similar way of deriving the endpoints presented in +[Creating ADRS (Including Non-standard Endpoints)](adrs.html). Most of the endpoints +are derived by calling `admiral::derive_extreme_event()`. Thus the examples in this +vignette can also be used as a starting point for implementing response criteria other +than iRECIST 1.1, e.g., RECIST 1.1 or International Myeloma Working Group (IMWG) +criteria for the diagnosis of multiple myeloma. + +For more information on the iRECIST guidelines user may visit +https://recist.eortc.org/recist-1-1-2/ + +Examples are currently presented and tested using `ADSL` (ADaM) and +`RS` (SDTM) inputs. However, other domains could be used. The functions +and workflow could similarly be used to create an intermediary `ADEVENT` ADaM. + +**Note**: *All examples assume CDISC SDTM and/or ADaM format as input +unless otherwise specified.* + +# Programming Workflow + +- [Read in Data](#readdata) +- [Pre-processing of Input Records](#input) +- [Derive Confirmed Progressive Disease Parameter](#pd) +- [Derive Response Parameter](#rsp) +- [Derive Clinical Benefit Parameter](#cb) +- [Derive Best Overall Response Parameter](#bor) +- [Derive Response Parameters requiring Confirmation](#confirm) + +## Read in Data {#readdata} + +To start, all data frames needed for the creation of `ADRS` should be +read into the environment. This will be a company specific process. Some +of the data frames needed may be `ADSL`, `RS` and `TU`. + +For example purpose, the SDTM and ADaM datasets (based on CDISC Pilot +test data)---which are included in `{pharmaversesdtm}` and `{pharmaverseadam}`---are used. + +```{r message=FALSE} +library(admiral) +library(admiralonco) +library(dplyr) +library(pharmaverseadam) +library(pharmaversesdtm) +library(lubridate) +library(stringr) +data("adsl") +data("rs_onco_irecist") + +adsl_onco <- adsl +rs <- rs_onco_irecist + +rs <- convert_blanks_to_na(rs) +``` + +```{r echo=FALSE} +# select subjects from adsl such that there is one subject without RS data +rs_subjects <- unique(rs$USUBJID) +adsl_subjects <- unique(adsl_onco$USUBJID) +adsl <- filter( + adsl_onco, + USUBJID %in% union(rs_subjects, setdiff(adsl_subjects, rs_subjects)[1]) +) +``` + +At this step, it may be useful to join `ADSL` to your `RS` domain. Only +the `ADSL` variables used for derivations are selected at this step. The +rest of the relevant `ADSL` would be added later. + +```{r eval=TRUE} +adsl_vars <- exprs(RANDDT) +adrs <- derive_vars_merged( + rs, + dataset_add = adsl, + new_vars = adsl_vars, + by_vars = exprs(STUDYID, USUBJID) +) +``` + +```{r, eval=TRUE, echo=FALSE} +dataset_vignette( + adrs, + display_vars = exprs(USUBJID, RSTESTCD, RSDTC, VISIT, RANDDT), + filter = RSTESTCD == "OVRLRESP" +) +``` + +## Pre-processing of Input Records {#input} + +The first step involves company-specific pre-processing of records for +the required input to the downstream parameter functions. It could involve +merging input data from other sources besides `RS`, such as `ADTR`. + +This step would include any required selection/derivation of `ADT` or +applying any necessary partial date imputations, updating `AVAL` (e.g. +this should be ordered from best to worst response), and setting +analysis flag `ANL01FL`. Common options for `ANL01FL` would be to set +null for invalid assessments or those occurring after new anti-cancer +therapy, or to only flag assessments on or after after date of first +treatment/randomization, or rules to cover the case when a patient has +multiple observations per visit (e.g. by selecting worst value). Another +consideration could be extra potential protocol-specific sources of +Progressive Disease such as radiological assessments, which could be +pre-processed here to create a PD record to feed downstream derivations. + +For the derivation of the parameters it is expected that the subject +identifier variables (usually `STUDYID` and `USUBJID`) and `ADT` are a +unique key. This can be achieved by deriving an analysis flag +(`ANLzzFL`). See [Derive `ANL01FL`](#anl01fl) for an example. + +The below shows an example of a possible company-specific implementation +of this step. + +### Select Overall Response Records and Set Parameter Details + +In this case we use the overall response records from `RS` from the +investigator as our starting point. The parameter details such as +`PARAMCD`, `PARAM` etc will always be company-specific, but an example +is shown below so that you can trace through how these records feed into +the other parameter derivations. + +```{r} +adrs <- adrs %>% + filter(RSEVAL == "INVESTIGATOR" & RSTESTCD == "OVRLRESP") %>% + mutate( + PARAMCD = "OVR", + PARAM = "Overall Response by Investigator", + PARCAT1 = "Tumor Response", + PARCAT2 = "Investigator", + PARCAT3 = "iRecist" + ) +``` + +```{r, echo=FALSE} +dataset_vignette( + adrs, + display_vars = exprs(USUBJID, VISIT, RSTESTCD, RSEVAL, PARAMCD, PARAM, PARCAT1, PARCAT2, PARCAT3) +) +``` + +### Partial Date Imputation and Deriving `ADT`, `ADTF`, `AVISIT` etc + +If your data collection allows for partial dates, you could apply a +company-specific imputation rule at this stage when deriving `ADT`. For +this example, here we impute missing day to last possible date. + +```{r} +adrs <- adrs %>% + derive_vars_dt( + dtc = RSDTC, + new_vars_prefix = "A", + highest_imputation = "D", + date_imputation = "last" + ) %>% + mutate(AVISIT = VISIT) +``` + +```{r, echo=FALSE} +dataset_vignette( + adrs, + display_vars = exprs(USUBJID, AVISIT, PARAMCD, PARAM, RSSTRESC, RSDTC, ADT, ADTF) +) +``` + +### Derive `AVALC` and `AVAL` + +Here we populate `AVALC` and create the numeric version as `AVAL` +(ordered from best to worst response). The `AVAL` values are not considered in +the parameter derivations below, and so changing `AVAL` here would not change +the result of those derivations. + +iRECIST ordering will be used or if you'd like to provide your own company-specific ordering here you +could do this as follows: + +```{r} +aval_resp_new <- function(arg) { + case_when( + arg == "iCR" ~ 8, + arg == "iPR" ~ 7, + arg == "iSD" ~ 6, + arg == "NON-iCR/NON-iUPD" ~ 5, + arg == "iCPD" ~ 4, + arg == "iUPD" ~ 3, + arg == "NE" ~ 2, + arg == "MISSING" ~ 1, + TRUE ~ NA_real_ + ) +} + +adrs <- adrs %>% + mutate( + AVALC = RSSTRESC, + AVAL = aval_resp_new(AVALC) + ) +``` + +```{r, echo=FALSE} +dataset_vignette( + adrs, + display_vars = exprs(USUBJID, AVISIT, PARAMCD, PARAM, RSSTRESC, AVALC, AVAL) +) +``` + +### Flag Worst Assessment at Each Date (`ANL01FL`) {#anl01fl} + +When deriving `ANL01FL` this is an opportunity to exclude any records +that should not contribute to any downstream parameter derivations. In +the below example this includes only selecting valid assessments and +those occurring on or after randomization date. If there is more than +one assessment at a date, the worst one is flagged. + +```{r} +adrs <- adrs %>% + restrict_derivation( + derivation = derive_var_extreme_flag, + args = params( + by_vars = exprs(STUDYID, USUBJID, ADT), + order = exprs(AVAL, RSSEQ), + new_var = ANL01FL, + mode = "last" + ), + filter = !is.na(AVAL) & ADT >= RANDDT + ) +``` + +```{r, echo=FALSE} +dataset_vignette( + adrs, + display_vars = exprs(USUBJID, AVISIT, PARAMCD, PARAM, AVALC, ADT, RANDDT, ANL01FL) +) +``` + +Here is an alternative example where those records occurring after new +anti-cancer therapy are additionally excluded (where `NACTDT` would be +pre-derived as first date of new anti-cancer therapy. See `{admiralonco}` +[Creating and Using New Anti-Cancer Start Date](nactdt.html) for deriving this +variable). + +```{r, eval=FALSE} +adrs <- adrs %>% + mutate( + ANL01FL = case_when( + !is.na(AVAL) & ADT >= RANDDT & ADT < NACTDT ~ "Y", + TRUE ~ NA_character_ + ) + ) +``` + +### Flag Assessments up to First PD (`ANL02FL`) {#anl02fl} + +To restrict response data up to and including first reported progressive disease +`ANL02FL` flag could be created by using `{admiral}` function +`admiral::derive_var_relative_flag()`. + +```{r} +adrs <- adrs %>% + derive_var_relative_flag( + by_vars = exprs(STUDYID, USUBJID), + order = exprs(ADT, RSSEQ), + new_var = ANL02FL, + condition = AVALC == "iCPD", + mode = "first", + selection = "before", + inclusive = TRUE + ) +``` + +```{r, echo=FALSE} +dataset_vignette( + adrs, + display_vars = exprs(USUBJID, AVISIT, PARAMCD, AVALC, ADT, ANL01FL, ANL02FL) +) +``` + +### Select Source Assessments for Parameter derivations + +For most parameter derivations the post-baseline overall response assessments up +to and including first PD are considered. +```{r} +ovr <- filter(adrs, PARAMCD == "OVR" & ANL01FL == "Y" & ANL02FL == "Y") +``` + +```{r, echo=FALSE} +dataset_vignette( + ovr, + display_vars = exprs(USUBJID, AVISIT, AVALC, ADT, RANDDT) +) +``` + +## Define Events + +The building blocks for the events that contribute to deriving common endpoints +like what constitutes a responder, or a Best Overall Response of complete +response (CR), ... are predefined in admiralonco for Recist 1.1 (see [Pre-Defined +Response Event Objects](../reference/event_objects.html)). New Response Event Objects +are needed for iRECIST and any study-specific needs. Here the confirmation period +and the `keep_source_vars` argument is updated, as well as the `first_cond` and `condition` for the iRECIST values. + +```{r} +confirmation_period <- 21 + +icbor_icr <- event_joined( + description = paste( + "Define complete response (iCR) for confirmed best overall response (iCBOR) as", + "iCR followed by iCR at least", + confirmation_period, + "days later and at most one NE in between" + ), + dataset_name = "ovr", + join_vars = exprs(AVALC, ADT), + join_type = "after", + first_cond = AVALC.join == "iCR" & + ADT.join >= ADT + confirmation_period, + condition = AVALC == "iCR" & + all(AVALC.join %in% c("iCR", "NE")) & + count_vals(var = AVALC.join, val = "NE") <= 1, + set_values_to = exprs(AVALC = "iCR") +) + +icbor_ipr <- event_joined( + description = paste( + "Define partial response (iPR) for confirmed best overall response (iCBOR) as", + "iPR followed by iCR or iPR at least", + confirmation_period, + "28 days later, at most one NE in between, and no iPR after iCR" + ), + dataset_name = "ovr", + join_vars = exprs(AVALC, ADT), + join_type = "after", + first_cond = AVALC.join %in% c("iCR", "iPR") & + ADT.join >= ADT + confirmation_period, + condition = AVALC == "iPR" & + all(AVALC.join %in% c("iCR", "iPR", "NE")) & + count_vals(var = AVALC.join, val = "NE") <= 1 & + ( + min_cond( + var = ADT.join, + cond = AVALC.join == "iCR" + ) > max_cond(var = ADT.join, cond = AVALC.join == "iPR") | + count_vals(var = AVALC.join, val = "iCR") == 0 | + count_vals(var = AVALC.join, val = "iPR") == 0 + ), + set_values_to = exprs(AVALC = "iPR") +) + +no_data_n <- event( + description = "Define no response for all patients in adsl (should be used as last event)", + dataset_name = "adsl", + condition = TRUE, + set_values_to = exprs(AVALC = "N"), + keep_source_vars = adsl_vars +) + +no_data_missing <- event( + description = paste( + "Define missing response (MISSING) for all patients in adsl (should be used", + "as last event)" + ), + dataset_name = "adsl", + condition = TRUE, + set_values_to = exprs(AVALC = "MISSING"), + keep_source_vars = adsl_vars +) +``` + +## Derive Confirmed Progressive Disease Parameter {#pd} + +Now that we have the input records prepared above with any +company-specific requirements, we can start to derive new parameter +records. For the parameter derivations, all values except those +overwritten by `set_values_to` argument are kept from the earliest +occurring input record fulfilling the required criteria. + +The function `admiral::derive_extreme_records()` can be used to find +the date of first `iCPD`. + +```{r} +adrs <- adrs %>% + derive_extreme_records( + dataset_ref = adsl, + dataset_add = adrs, + by_vars = exprs(STUDYID, USUBJID), + filter_add = PARAMCD == "OVR" & AVALC == "iCPD" & ANL01FL == "Y", + order = exprs(ADT, RSSEQ), + mode = "first", + exist_flag = AVALC, + set_values_to = exprs( + PARAMCD = "ICPD", + PARAM = "Immune Confirmation of Disease Progression by Investigator", + PARCAT1 = "Tumor Response", + PARCAT2 = "Investigator", + PARCAT3 = "iRecist", + AVAL = yn_to_numeric(AVALC), + ANL01FL = "Y" + ) + ) +``` + +```{r, echo=FALSE} +dataset_vignette( + adrs, + display_vars = exprs(USUBJID, AVISIT, PARAMCD, PARAM, AVALC, ADT, ANL01FL), + filter = PARAMCD == "ICPD" +) +``` + +For progressive disease response shown in steps here and below, in our +examples we show these as `ADRS` parameters, but they could equally be +achieved via `ADSL` dates or `ADEVENT` parameters.If you prefer to store +as an ADSL date, then the function `admiral::derive_var_extreme_dt()` +could be used to find the date of first `iCPD` as a variable, rather than +as a new parameter record. + +## Derive Response Parameter {#rsp} + +The function `admiral::derive_extreme_event()` can then be used to find the date +of first response. In the below example, the response condition has been defined +as `iCR` or `iPR` via the event `irsp_y` that was created for iRECIST. + + + +```{r} +irsp_y <- event( + description = "Define iCR or iPR as (unconfirmed) response", + dataset_name = "ovr", + condition = AVALC %in% c("iCR", "iPR"), + set_values_to = exprs(AVALC = "Y") +) +``` + +```{r} +adrs <- adrs %>% + derive_extreme_event( + by_vars = exprs(STUDYID, USUBJID), + order = exprs(ADT), + mode = "first", + events = list(irsp_y, no_data_n), + source_datasets = list( + ovr = ovr, + adsl = adsl + ), + set_values_to = exprs( + PARAMCD = "IRSP", + PARAM = "Immune Response by Investigator (confirmation not required)", + PARCAT1 = "Tumor Response", + PARCAT2 = "Investigator", + PARCAT3 = "iRecist", + AVAL = yn_to_numeric(AVALC), + ANL01FL = "Y" + ) + ) +``` + +```{r, echo=FALSE} +dataset_vignette( + adrs, + display_vars = exprs(USUBJID, AVISIT, PARAMCD, PARAM, AVALC, ADT, ANL01FL), + filter = PARAMCD == "IRSP" +) +``` + +## Derive Clinical Benefit Parameter {#cb} + +The function `admiral::derive_extreme_event()` can then be used to derive the +clinical benefit parameter, which we define as a patient having had a response +or a sustained period of time before first `iCPD`. This could also be known as +disease control. In this example the "sustained period" has been defined as 42 +days after randomization date via the created `icb_y` event. + + +```{r} +icb_y <- event( + description = paste( + "Define iCR, iPR, iSD, or NON-iCR/NON-iPD occuring at least 42 days after", + "randomization as clinical benefit" + ), + dataset_name = "ovr", + condition = AVALC %in% c("iCR", "iPR", "iSD", "NON-iCR/NON-iUPD") & + ADT >= RANDDT + 42, + set_values_to = exprs(AVALC = "Y") +) +``` + +Please note that the result `AVALC = "Y"` is defined by the first _two_ events +specified for `events`. For subjects with observations fulfilling both events +the one with the earlier date should be selected (and not the first one in the +list). Thus `ignore_event_order = TRUE` is specified. + +```{r} +adrs <- adrs %>% + derive_extreme_event( + by_vars = exprs(STUDYID, USUBJID), + order = exprs(desc(AVALC), ADT), + mode = "first", + events = list(irsp_y, icb_y, no_data_n), + source_datasets = list( + ovr = ovr, + adsl = adsl + ), + ignore_event_order = TRUE, + set_values_to = exprs( + PARAMCD = "ICB", + PARAM = "Immune Clinical Benefit by Investigator (confirmation for response not required)", + PARCAT1 = "Tumor Response", + PARCAT2 = "Investigator", + PARCAT3 = "iRecist", + AVAL = yn_to_numeric(AVALC), + ANL01FL = "Y" + ), + check_type = "none" + ) +``` + +```{r, echo=FALSE} +dataset_vignette( + adrs, + display_vars = exprs(USUBJID, AVISIT, PARAMCD, PARAM, AVALC, ADT, RANDDT, ANL01FL), + filter = PARAMCD == "ICB" +) +``` + +## Derive Best Overall Response Parameter {#bor} + +The function `admiral::derive_extreme_event()` can be used to derive the best +overall response (without confirmation required) parameter. Similar to the above +function you can optionally decide what period would you consider an `iSD` or +`NON-iCR/NON-iUPD` as being eligible from. In this example, 42 days after +randomization date has been used again. + +Please note that the order of the events specified for `events` is important. +For example, a subject with `iPR`, `iPR`, `iCR` qualifies for both `ibor_icr` and +`ibor_ipr`. As `ibor_icr` is listed before `ibor_ipr`, `iCR` is selected as best overall +response for this subject. + +```{r} +ibor_icr <- event( + description = "Define complete response (iCR) for best overall response (iBOR)", + dataset_name = "ovr", + condition = AVALC == "iCR", + set_values_to = exprs(AVALC = "iCR") +) + +ibor_ipr <- event( + description = "Define partial response (iPR) for best overall response (iBOR)", + dataset_name = "ovr", + condition = AVALC == "iPR", + set_values_to = exprs(AVALC = "iPR") +) + +ibor_isd <- event( + description = paste( + "Define stable disease (iSD) for best overall response (iBOR) as iCR, iPR, or iSD", + "occurring at least 42 days after randomization" + ), + dataset_name = "ovr", + condition = AVALC %in% c("iCR", "iPR", "iSD") & ADT >= RANDDT + 42, + set_values_to = exprs(AVALC = "iSD") +) + +ibor_non_icripd <- event( + description = paste( + "Define NON-iCR/NON-iUPD for best overall response (iBOR) as NON-iCR/NON-iUPD", + "occuring at least 42 days after randomization" + ), + dataset_name = "ovr", + condition = AVALC == "NON-iCR/NON-iUPD" & ADT >= RANDDT + 42, + set_values_to = exprs(AVALC = "NON-iCR/NON-iUPD") +) + +ibor_icpd <- event( + description = "Define progressive disease (iCPD) for best overall response (iBOR)", + dataset_name = "ovr", + condition = AVALC == "iCPD", + set_values_to = exprs(AVALC = "iCPD") +) + +ibor_iupd <- event( + description = "Define progressive disease (iUPD) for best overall response (iBOR)", + dataset_name = "ovr", + condition = AVALC == "iUPD", + set_values_to = exprs(AVALC = "iUPD") +) + +ibor_ne <- event( + description = paste( + "Define not evaluable (NE) for best overall response (iBOR) as iSD, NON-iCR/NON-iUPD,", + "or NE (should be specified after ibor_isd and ibor_non_icripd)" + ), + dataset_name = "ovr", + condition = AVALC %in% c("iSD", "NON-iCR/NON-iUPD", "NE"), + set_values_to = exprs(AVALC = "NE") +) + + +adrs <- adrs %>% + derive_extreme_event( + by_vars = exprs(STUDYID, USUBJID), + order = exprs(ADT), + mode = "first", + source_datasets = list( + ovr = ovr, + adsl = adsl + ), + events = list(ibor_icr, ibor_ipr, ibor_isd, ibor_non_icripd, ibor_icpd, ibor_iupd, ibor_ne, no_data_missing), + set_values_to = exprs( + PARAMCD = "IBOR", + PARAM = "Immune Best Overall Response by Investigator (confirmation not required)", + PARCAT1 = "Tumor Response", + PARCAT2 = "Investigator", + PARCAT3 = "iRecist", + AVAL = aval_resp_new(AVALC), + ANL01FL = "Y" + ) + ) +``` + +```{r, echo=FALSE} +dataset_vignette( + adrs, + display_vars = exprs(USUBJID, AVISIT, PARAMCD, PARAM, AVALC, ADT, RANDDT, ANL01FL), + filter = PARAMCD == "IBOR" +) +``` + +## Derive Response Parameters requiring Confirmation {#confirm} + +Any of the above response parameters can be repeated for "confirmed" responses +only. For these the function `admiral::derive_extreme_event()` can be used with +different events. Some of the other functions from above can then be re-used +passing in these confirmed response records. See the examples below of derived +parameters requiring confirmation. The assessment and the confirmatory +assessment here need to occur at least 28 days apart *(without any +1 applied to +this calculation of days between visits)*, using the `icrsp_y_cr`[^1], +`icrsp_y_ipr`[^2], `icbor_icr`[^3], and `icbor_ipr`[^4] event. + +[^1]: +```{r} +icrsp_y_icr <- event_joined( + description = paste( + "Define confirmed response as iCR followed by CR at least 28 days later and", + "at most one NE in between" + ), + dataset_name = "ovr", + join_vars = exprs(AVALC, ADT), + join_type = "after", + order = exprs(ADT), + first_cond = AVALC.join == "CR" & + ADT.join >= ADT + days(28), + condition = AVALC == "iCR" & + all(AVALC.join %in% c("iCR", "NE")) & + count_vals(var = AVALC.join, val = "NE") <= 1, + set_values_to = exprs(AVALC = "Y") +) +``` +[^2]: +```{r} +icrsp_y_ipr <- event_joined( + description = paste( + "Define confirmed response as iPR followed by iCR or PR at least 28 days later,", + "at most one NE in between, and no iPR after iCR" + ), + dataset_name = "ovr", + join_vars = exprs(AVALC, ADT), + join_type = "after", + order = exprs(ADT), + first_cond = AVALC.join %in% c("iCR", "iPR") & + ADT.join >= ADT + days(28), + condition = AVALC == "iPR" & + all(AVALC.join %in% c("iCR", "iPR", "NE")) & + count_vals(var = AVALC.join, val = "NE") <= 1 & + ( + min_cond( + var = ADT.join, + cond = AVALC.join == "iCR" + ) > max_cond(var = ADT.join, cond = AVALC.join == "iPR") | + count_vals(var = AVALC.join, val = "iCR") == 0 | + count_vals(var = AVALC.join, val = "iPR") == 0 + ), + set_values_to = exprs(AVALC = "Y") +) +``` +[^3]: +```{r} +icbor_icr <- event_joined( + description = paste( + "Define complete response (iCR) for confirmed best overall response (ICBOR) as", + "iCR followed by iCR at least 28 days later and at most one NE in between" + ), + dataset_name = "ovr", + join_vars = exprs(AVALC, ADT), + join_type = "after", + first_cond = AVALC.join == "iCR" & + ADT.join >= ADT + 28, + condition = AVALC == "iCR" & + all(AVALC.join %in% c("iCR", "NE")) & + count_vals(var = AVALC.join, val = "NE") <= 1, + set_values_to = exprs(AVALC = "iCR") +) +``` +[^4]: +```{r} +icbor_ipr <- event_joined( + description = paste( + "Define partial response (iPR) for confirmed best overall response (ICBOR) as", + "iPR followed by iCR or iPR at least 28 days later, at most one NE in between,", + "and no iPR after iCR" + ), + dataset_name = "ovr", + join_vars = exprs(AVALC, ADT), + join_type = "after", + first_cond = AVALC.join %in% c("iCR", "iPR") & + ADT.join >= ADT + 28, + condition = AVALC == "iPR" & + all(AVALC.join %in% c("iCR", "iPR", "NE")) & + count_vals(var = AVALC.join, val = "NE") <= 1 & + ( + min_cond( + var = ADT.join, + cond = AVALC.join == "iCR" + ) > max_cond(var = ADT.join, cond = AVALC.join == "iPR") | + count_vals(var = AVALC.join, val = "iCR") == 0 | + count_vals(var = AVALC.join, val = "iPR") == 0 + ), + set_values_to = exprs(AVALC = "iPR") +) +``` + +Please note that the result `AVALC = "Y"` for confirmed clinical benefit is +defined by the first _two_ events specified for `events`. For subjects with +observations fulfilling both events the one with the earlier date should be +selected (and not the first one in the list). Thus `ignore_event_order = TRUE` +is specified. + +```{r} +adrs <- adrs %>% + derive_extreme_event( + by_vars = exprs(STUDYID, USUBJID), + order = exprs(desc(AVALC), ADT), + mode = "first", + source_datasets = list( + ovr = ovr, + adsl = adsl + ), + events = list(icrsp_y_icr, icrsp_y_ipr, no_data_n), + ignore_event_order = TRUE, + set_values_to = exprs( + PARAMCD = "ICRSP", + PARAM = "Immune Response by Investigator (confirmation required)", + PARCAT1 = "Tumor Response", + PARCAT2 = "Investigator", + PARCAT3 = "iRecist", + AVAL = yn_to_numeric(AVALC), + ANL01FL = "Y" + ) + ) + +adrs <- adrs %>% + derive_extreme_event( + by_vars = exprs(STUDYID, USUBJID), + order = exprs(desc(AVALC), ADT), + mode = "first", + events = list(icrsp_y_icr, icrsp_y_ipr, icb_y, no_data_n), + source_datasets = list( + ovr = ovr, + adsl = adsl + ), + ignore_event_order = TRUE, + set_values_to = exprs( + PARAMCD = "ICCB", + PARAM = "Immune Clinical Benefit by Investigator (confirmation required)", + PARCAT1 = "Tumor Response", + PARCAT2 = "Investigator", + PARCAT3 = "iRecist", + AVAL = yn_to_numeric(AVALC), + ANL01FL = "Y" + ), + check_type = "none" + ) + +adrs <- adrs %>% + derive_extreme_event( + by_vars = exprs(STUDYID, USUBJID), + order = exprs(ADT), + mode = "first", + events = list(icbor_icr, icbor_ipr, ibor_isd, ibor_non_icripd, ibor_icpd, ibor_iupd, ibor_ne, no_data_missing), + source_datasets = list( + ovr = ovr, + adsl = adsl + ), + set_values_to = exprs( + PARAMCD = "ICBOR", + PARAM = "Immune Best Overall Response by Investigator (confirmation required)", + PARCAT1 = "Tumor Response", + PARCAT2 = "Investigator", + PARCAT3 = "Recist 1.1", + AVAL = aval_resp(AVALC), + ANL01FL = "Y" + ) + ) +``` + +```{r, echo=FALSE} +dataset_vignette( + adrs, + display_vars = exprs(USUBJID, AVISIT, PARAMCD, PARAM, AVALC, ADT, RANDDT, ANL01FL), + filter = PARAMCD %in% c("ICRSP", "ICCB", "ICBOR") +) +``` From 70e5350a9ae045fa1b50ae3efc3b145e8305ca88 Mon Sep 17 00:00:00 2001 From: Vinh Nguyen Date: Wed, 15 Nov 2023 13:58:46 -0500 Subject: [PATCH 02/14] 233 - irecist vignette review update 1 --- vignettes/irecist.Rmd | 64 ++++++++++++++++++++++++------------------- 1 file changed, 36 insertions(+), 28 deletions(-) diff --git a/vignettes/irecist.Rmd b/vignettes/irecist.Rmd index 77968cf5..957c8e38 100644 --- a/vignettes/irecist.Rmd +++ b/vignettes/irecist.Rmd @@ -52,13 +52,10 @@ library(admiraldev) This article describes creating an `ADRS` ADaM with oncology endpoint parameters based on iRECIST. It shows a similar way of deriving the endpoints presented in [Creating ADRS (Including Non-standard Endpoints)](adrs.html). Most of the endpoints -are derived by calling `admiral::derive_extreme_event()`. Thus the examples in this -vignette can also be used as a starting point for implementing response criteria other -than iRECIST 1.1, e.g., RECIST 1.1 or International Myeloma Working Group (IMWG) -criteria for the diagnosis of multiple myeloma. +are derived by calling `admiral::derive_extreme_event()`. For more information on the iRECIST guidelines user may visit -https://recist.eortc.org/recist-1-1-2/ +https://recist.eortc.org/irecist/ Examples are currently presented and tested using `ADSL` (ADaM) and `RS` (SDTM) inputs. However, other domains could be used. The functions @@ -76,6 +73,7 @@ unless otherwise specified.* - [Derive Clinical Benefit Parameter](#cb) - [Derive Best Overall Response Parameter](#bor) - [Derive Response Parameters requiring Confirmation](#confirm) +- [Other Endpoints](#Other) ## Read in Data {#readdata} @@ -95,9 +93,9 @@ library(pharmaversesdtm) library(lubridate) library(stringr) data("adsl") +# iRECIST oncology data data("rs_onco_irecist") -adsl_onco <- adsl rs <- rs_onco_irecist rs <- convert_blanks_to_na(rs) @@ -106,9 +104,9 @@ rs <- convert_blanks_to_na(rs) ```{r echo=FALSE} # select subjects from adsl such that there is one subject without RS data rs_subjects <- unique(rs$USUBJID) -adsl_subjects <- unique(adsl_onco$USUBJID) +adsl_subjects <- unique(adsl$USUBJID) adsl <- filter( - adsl_onco, + adsl, USUBJID %in% union(rs_subjects, setdiff(adsl_subjects, rs_subjects)[1]) ) ``` @@ -138,8 +136,11 @@ dataset_vignette( ## Pre-processing of Input Records {#input} The first step involves company-specific pre-processing of records for -the required input to the downstream parameter functions. It could involve -merging input data from other sources besides `RS`, such as `ADTR`. +the required input to the downstream parameter functions. Note that this +could be needed multiple times (e.g. once for investigator and once for +Independent Review Facility (IRF)/Blinded Independent Central Review +(BICR) records). It could even involve merging input data from other +sources besides `RS`, such as `ADTR`. This step would include any required selection/derivation of `ADT` or applying any necessary partial date imputations, updating `AVAL` (e.g. @@ -296,7 +297,7 @@ adrs <- adrs %>% ) ``` -### Flag Assessments up to First PD (`ANL02FL`) {#anl02fl} +### Flag Assessments up to First iCPD (`ANL02FL`) {#anl02fl} To restrict response data up to and including first reported progressive disease `ANL02FL` flag could be created by using `{admiral}` function @@ -372,7 +373,7 @@ icbor_ipr <- event_joined( "Define partial response (iPR) for confirmed best overall response (iCBOR) as", "iPR followed by iCR or iPR at least", confirmation_period, - "28 days later, at most one NE in between, and no iPR after iCR" + "days later, at most one NE in between, and no iPR after iCR" ), dataset_name = "ovr", join_vars = exprs(AVALC, ADT), @@ -454,7 +455,7 @@ dataset_vignette( ) ``` -For progressive disease response shown in steps here and below, in our +For progressive disease and response shown in steps here and below, in our examples we show these as `ADRS` parameters, but they could equally be achieved via `ADSL` dates or `ADEVENT` parameters.If you prefer to store as an ADSL date, then the function `admiral::derive_var_extreme_dt()` @@ -513,7 +514,7 @@ dataset_vignette( The function `admiral::derive_extreme_event()` can then be used to derive the clinical benefit parameter, which we define as a patient having had a response -or a sustained period of time before first `iCPD`. This could also be known as +or a sustained period of time before first `iUPD`. This could also be known as disease control. In this example the "sustained period" has been defined as 42 days after randomization date via the created `icb_y` event. @@ -521,7 +522,7 @@ days after randomization date via the created `icb_y` event. ```{r} icb_y <- event( description = paste( - "Define iCR, iPR, iSD, or NON-iCR/NON-iPD occuring at least 42 days after", + "Define iCR, iPR, iSD, or NON-iCR/NON-iUPD occuring at least 42 days after", "randomization as clinical benefit" ), dataset_name = "ovr", @@ -618,14 +619,14 @@ ibor_non_icripd <- event( ) ibor_icpd <- event( - description = "Define progressive disease (iCPD) for best overall response (iBOR)", + description = "Define confirmed progressive disease (iCPD) for best overall response (iBOR)", dataset_name = "ovr", condition = AVALC == "iCPD", set_values_to = exprs(AVALC = "iCPD") ) ibor_iupd <- event( - description = "Define progressive disease (iUPD) for best overall response (iBOR)", + description = "Define unconfirmed progressive disease (iUPD) for best overall response (iBOR)", dataset_name = "ovr", condition = AVALC == "iUPD", set_values_to = exprs(AVALC = "iUPD") @@ -685,17 +686,18 @@ this calculation of days between visits)*, using the `icrsp_y_cr`[^1], [^1]: ```{r} +confirmation_period <- 28 icrsp_y_icr <- event_joined( description = paste( - "Define confirmed response as iCR followed by CR at least 28 days later and", + "Define confirmed response as iCR followed by iCR at least 28 days later and", "at most one NE in between" ), dataset_name = "ovr", join_vars = exprs(AVALC, ADT), join_type = "after", order = exprs(ADT), - first_cond = AVALC.join == "CR" & - ADT.join >= ADT + days(28), + first_cond = AVALC.join == "iCR" & + ADT.join >= ADT + days(confirmation_period), condition = AVALC == "iCR" & all(AVALC.join %in% c("iCR", "NE")) & count_vals(var = AVALC.join, val = "NE") <= 1, @@ -704,9 +706,10 @@ icrsp_y_icr <- event_joined( ``` [^2]: ```{r} +confirmation_period <- 28 icrsp_y_ipr <- event_joined( description = paste( - "Define confirmed response as iPR followed by iCR or PR at least 28 days later,", + "Define confirmed response as iPR followed by iCR or iPR at least 28 days later,", "at most one NE in between, and no iPR after iCR" ), dataset_name = "ovr", @@ -714,7 +717,7 @@ icrsp_y_ipr <- event_joined( join_type = "after", order = exprs(ADT), first_cond = AVALC.join %in% c("iCR", "iPR") & - ADT.join >= ADT + days(28), + ADT.join >= ADT + days(confirmation_period), condition = AVALC == "iPR" & all(AVALC.join %in% c("iCR", "iPR", "NE")) & count_vals(var = AVALC.join, val = "NE") <= 1 & @@ -731,16 +734,17 @@ icrsp_y_ipr <- event_joined( ``` [^3]: ```{r} +confirmation_period <- 28 icbor_icr <- event_joined( description = paste( - "Define complete response (iCR) for confirmed best overall response (ICBOR) as", + "Define complete response (iCR) for confirmed best overall response (iCBOR) as", "iCR followed by iCR at least 28 days later and at most one NE in between" ), dataset_name = "ovr", join_vars = exprs(AVALC, ADT), join_type = "after", first_cond = AVALC.join == "iCR" & - ADT.join >= ADT + 28, + ADT.join >= ADT + confirmation_period, condition = AVALC == "iCR" & all(AVALC.join %in% c("iCR", "NE")) & count_vals(var = AVALC.join, val = "NE") <= 1, @@ -749,9 +753,10 @@ icbor_icr <- event_joined( ``` [^4]: ```{r} +confirmation_period <- 28 icbor_ipr <- event_joined( description = paste( - "Define partial response (iPR) for confirmed best overall response (ICBOR) as", + "Define partial response (iPR) for confirmed best overall response (iCBOR) as", "iPR followed by iCR or iPR at least 28 days later, at most one NE in between,", "and no iPR after iCR" ), @@ -759,7 +764,7 @@ icbor_ipr <- event_joined( join_vars = exprs(AVALC, ADT), join_type = "after", first_cond = AVALC.join %in% c("iCR", "iPR") & - ADT.join >= ADT + 28, + ADT.join >= ADT + confirmation_period, condition = AVALC == "iPR" & all(AVALC.join %in% c("iCR", "iPR", "NE")) & count_vals(var = AVALC.join, val = "NE") <= 1 & @@ -842,17 +847,20 @@ adrs <- adrs %>% PARAM = "Immune Best Overall Response by Investigator (confirmation required)", PARCAT1 = "Tumor Response", PARCAT2 = "Investigator", - PARCAT3 = "Recist 1.1", + PARCAT3 = "iRecist", AVAL = aval_resp(AVALC), ANL01FL = "Y" ) ) ``` -```{r, echo=FALSE} +```{r, eval=TRUE, echo=FALSE} dataset_vignette( adrs, display_vars = exprs(USUBJID, AVISIT, PARAMCD, PARAM, AVALC, ADT, RANDDT, ANL01FL), filter = PARAMCD %in% c("ICRSP", "ICCB", "ICBOR") ) ``` +## Other Endpoints {#other} + +For additional endpoints that can be added please see [Creating ADRS (Including Non-standard Endpoints)](adrs.html). From 10f3aa4cd57fe99e6956671cfb76c7a9a0d7460e Mon Sep 17 00:00:00 2001 From: Vinh Nguyen Date: Sun, 19 Nov 2023 20:41:19 -0500 Subject: [PATCH 03/14] 233 - iRECIST vignette - addressed 1st round comments --- vignettes/irecist.Rmd | 221 ++++++++++++++++++++++-------------------- 1 file changed, 116 insertions(+), 105 deletions(-) diff --git a/vignettes/irecist.Rmd b/vignettes/irecist.Rmd index 957c8e38..ad42eae3 100644 --- a/vignettes/irecist.Rmd +++ b/vignettes/irecist.Rmd @@ -54,12 +54,16 @@ based on iRECIST. It shows a similar way of deriving the endpoints presented in [Creating ADRS (Including Non-standard Endpoints)](adrs.html). Most of the endpoints are derived by calling `admiral::derive_extreme_event()`. -For more information on the iRECIST guidelines user may visit +This vignette follows the iRECIST guidelines, for more information user may visit https://recist.eortc.org/irecist/ Examples are currently presented and tested using `ADSL` (ADaM) and -`RS` (SDTM) inputs. However, other domains could be used. The functions -and workflow could similarly be used to create an intermediary `ADEVENT` ADaM. +`RS` (SDTM) inputs. However, other domains could be used. The `RS` test data +contains iRECIST response for target, non-target and overall response. Further +pre-processing and considerations may be needed if iRECIST are only collected +after RECIST 1.1 progression and input data contains multiple response criteria. +The functions and workflow could similarly be used to create an intermediary +`ADEVENT` ADaM. **Note**: *All examples assume CDISC SDTM and/or ADaM format as input unless otherwise specified.* @@ -93,7 +97,7 @@ library(pharmaversesdtm) library(lubridate) library(stringr) data("adsl") -# iRECIST oncology data +# iRECIST oncology sdtm data data("rs_onco_irecist") rs <- rs_onco_irecist @@ -178,7 +182,7 @@ adrs <- adrs %>% PARAM = "Overall Response by Investigator", PARCAT1 = "Tumor Response", PARCAT2 = "Investigator", - PARCAT3 = "iRecist" + PARCAT3 = "iRECIST" ) ``` @@ -230,8 +234,8 @@ aval_resp_new <- function(arg) { arg == "iPR" ~ 7, arg == "iSD" ~ 6, arg == "NON-iCR/NON-iUPD" ~ 5, - arg == "iCPD" ~ 4, - arg == "iUPD" ~ 3, + arg == "iUPD" ~ 4, + arg == "iCPD" ~ 3, arg == "NE" ~ 2, arg == "MISSING" ~ 1, TRUE ~ NA_real_ @@ -270,7 +274,7 @@ adrs <- adrs %>% new_var = ANL01FL, mode = "last" ), - filter = !is.na(AVAL) & ADT >= RANDDT + filter = !is.na(AVAL) & AVALC !="MISSING" & ADT >= RANDDT ) ``` @@ -326,7 +330,7 @@ dataset_vignette( ### Select Source Assessments for Parameter derivations For most parameter derivations the post-baseline overall response assessments up -to and including first PD are considered. +to and including first iCPD are considered. ```{r} ovr <- filter(adrs, PARAMCD == "OVR" & ANL01FL == "Y" & ANL02FL == "Y") ``` @@ -344,54 +348,33 @@ The building blocks for the events that contribute to deriving common endpoints like what constitutes a responder, or a Best Overall Response of complete response (CR), ... are predefined in admiralonco for Recist 1.1 (see [Pre-Defined Response Event Objects](../reference/event_objects.html)). New Response Event Objects -are needed for iRECIST and any study-specific needs. Here the confirmation period -and the `keep_source_vars` argument is updated, as well as the `first_cond` and `condition` for the iRECIST values. +are needed for iRECIST and any study-specific needs. ```{r} -confirmation_period <- 21 - -icbor_icr <- event_joined( +icpd_y <- event_joined( description = paste( - "Define complete response (iCR) for confirmed best overall response (iCBOR) as", - "iCR followed by iCR at least", - confirmation_period, - "days later and at most one NE in between" + "Define confirmed progressive disease (iCPD) as", + "iUPD followed by iCPD with only other iUPD and NE responses in between" ), dataset_name = "ovr", join_vars = exprs(AVALC, ADT), join_type = "after", - first_cond = AVALC.join == "iCR" & - ADT.join >= ADT + confirmation_period, - condition = AVALC == "iCR" & - all(AVALC.join %in% c("iCR", "NE")) & - count_vals(var = AVALC.join, val = "NE") <= 1, - set_values_to = exprs(AVALC = "iCR") + first_cond_upper = AVALC.join == "iCPD", + condition = AVALC == "iUPD" & + all(AVALC.join %in% c("iCPD", "iUPD", "NE" )), + set_values_to = exprs(AVALC = "Y") ) -icbor_ipr <- event_joined( +iupd_y <- event_joined( description = paste( - "Define partial response (iPR) for confirmed best overall response (iCBOR) as", - "iPR followed by iCR or iPR at least", - confirmation_period, - "days later, at most one NE in between, and no iPR after iCR" + "Define unconfirmed progressive disease (iUPD) as", + "iUPD followed only by other iUPD or NE responses" ), dataset_name = "ovr", join_vars = exprs(AVALC, ADT), - join_type = "after", - first_cond = AVALC.join %in% c("iCR", "iPR") & - ADT.join >= ADT + confirmation_period, - condition = AVALC == "iPR" & - all(AVALC.join %in% c("iCR", "iPR", "NE")) & - count_vals(var = AVALC.join, val = "NE") <= 1 & - ( - min_cond( - var = ADT.join, - cond = AVALC.join == "iCR" - ) > max_cond(var = ADT.join, cond = AVALC.join == "iPR") | - count_vals(var = AVALC.join, val = "iCR") == 0 | - count_vals(var = AVALC.join, val = "iPR") == 0 - ), - set_values_to = exprs(AVALC = "iPR") + join_type = "all", + condition = ADT <= ADT.join & AVALC == "iUPD" & all(AVALC.join %in% c("iUPD", "NE")), + set_values_to = exprs(AVALC = "Y") ) no_data_n <- event( @@ -412,9 +395,10 @@ no_data_missing <- event( set_values_to = exprs(AVALC = "MISSING"), keep_source_vars = adsl_vars ) + ``` -## Derive Confirmed Progressive Disease Parameter {#pd} +## Derive Confirmed and Unconfirmed Progressive Disease Parameter {#pd} Now that we have the input records prepared above with any company-specific requirements, we can start to derive new parameter @@ -422,36 +406,69 @@ records. For the parameter derivations, all values except those overwritten by `set_values_to` argument are kept from the earliest occurring input record fulfilling the required criteria. -The function `admiral::derive_extreme_records()` can be used to find -the date of first `iCPD`. +When an `iCPD` occurs,the date would be that of the first `iUPD`. +The function `admiral::derive_extreme_records()`, in conjunction with the event `icpd_y`, +could be used to find the date of the first `iUPD`. + +For the Unconfirmed Progressive Disease Parameter, it can be of interest to look at `iUPD` that has +never been confirmed and no subsequent `iSD`, `iPR` or `iCR` has been observed. ```{r} adrs <- adrs %>% - derive_extreme_records( - dataset_ref = adsl, - dataset_add = adrs, + derive_extreme_event( by_vars = exprs(STUDYID, USUBJID), - filter_add = PARAMCD == "OVR" & AVALC == "iCPD" & ANL01FL == "Y", - order = exprs(ADT, RSSEQ), + order = exprs(ADT), mode = "first", - exist_flag = AVALC, + source_datasets = list( + ovr = ovr, + adsl = adsl + ), + events = list(icpd_y, no_data_n), set_values_to = exprs( PARAMCD = "ICPD", PARAM = "Immune Confirmation of Disease Progression by Investigator", PARCAT1 = "Tumor Response", PARCAT2 = "Investigator", - PARCAT3 = "iRecist", + PARCAT3 = "iRECIST", AVAL = yn_to_numeric(AVALC), ANL01FL = "Y" ) ) + +ovr_orig <- ovr +ovr <- ovr %>% + group_by(USUBJID) %>% + filter(ADT >= max_cond(var = ADT, cond = AVALC == "iUPD")) %>% + ungroup(USUBJID) + +adrs <- adrs %>% + derive_extreme_event( + by_vars = exprs(STUDYID, USUBJID), + order = exprs(ADT), + mode = "first", + source_datasets = list( + ovr = ovr, + adsl = adsl + ), + events = list(iupd_y, no_data_n), + set_values_to = exprs( + PARAMCD = "IUPD", + PARAM = "Immune Unconfirmed Disease Progression by Investigator", + PARCAT1 = "Tumor Response", + PARCAT2 = "Investigator", + PARCAT3 = "iRECIST", + AVAL = yn_to_numeric(AVALC), + ANL01FL = "Y" + ) + ) +ovr <- ovr_orig ``` ```{r, echo=FALSE} dataset_vignette( adrs, display_vars = exprs(USUBJID, AVISIT, PARAMCD, PARAM, AVALC, ADT, ANL01FL), - filter = PARAMCD == "ICPD" + filter = PARAMCD %in% c("ICPD", "IUPD") ) ``` @@ -468,8 +485,6 @@ The function `admiral::derive_extreme_event()` can then be used to find the date of first response. In the below example, the response condition has been defined as `iCR` or `iPR` via the event `irsp_y` that was created for iRECIST. - - ```{r} irsp_y <- event( description = "Define iCR or iPR as (unconfirmed) response", @@ -477,9 +492,7 @@ irsp_y <- event( condition = AVALC %in% c("iCR", "iPR"), set_values_to = exprs(AVALC = "Y") ) -``` -```{r} adrs <- adrs %>% derive_extreme_event( by_vars = exprs(STUDYID, USUBJID), @@ -495,7 +508,7 @@ adrs <- adrs %>% PARAM = "Immune Response by Investigator (confirmation not required)", PARCAT1 = "Tumor Response", PARCAT2 = "Investigator", - PARCAT3 = "iRecist", + PARCAT3 = "iRECIST", AVAL = yn_to_numeric(AVALC), ANL01FL = "Y" ) @@ -518,7 +531,6 @@ or a sustained period of time before first `iUPD`. This could also be known as disease control. In this example the "sustained period" has been defined as 42 days after randomization date via the created `icb_y` event. - ```{r} icb_y <- event( description = paste( @@ -535,7 +547,7 @@ icb_y <- event( Please note that the result `AVALC = "Y"` is defined by the first _two_ events specified for `events`. For subjects with observations fulfilling both events the one with the earlier date should be selected (and not the first one in the -list). Thus `ignore_event_order = TRUE` is specified. +list). Thus `ignore_event_order` and `tmp_event_nr_var` are not specified. ```{r} adrs <- adrs %>% @@ -548,13 +560,12 @@ adrs <- adrs %>% ovr = ovr, adsl = adsl ), - ignore_event_order = TRUE, set_values_to = exprs( PARAMCD = "ICB", PARAM = "Immune Clinical Benefit by Investigator (confirmation for response not required)", PARCAT1 = "Tumor Response", PARCAT2 = "Investigator", - PARCAT3 = "iRecist", + PARCAT3 = "iRECIST", AVAL = yn_to_numeric(AVALC), ANL01FL = "Y" ), @@ -608,7 +619,7 @@ ibor_isd <- event( set_values_to = exprs(AVALC = "iSD") ) -ibor_non_icripd <- event( +ibor_non_icriupd <- event( description = paste( "Define NON-iCR/NON-iUPD for best overall response (iBOR) as NON-iCR/NON-iUPD", "occuring at least 42 days after randomization" @@ -618,13 +629,22 @@ ibor_non_icripd <- event( set_values_to = exprs(AVALC = "NON-iCR/NON-iUPD") ) -ibor_icpd <- event( - description = "Define confirmed progressive disease (iCPD) for best overall response (iBOR)", + +ibor_icpd <- event_joined( + description = paste( + "Define confirmed progressive disease (iCPD) for best overall response (iBOR) as", + "iUPD followed by iCPD with only other iUPD and NE responses in between" + ), dataset_name = "ovr", - condition = AVALC == "iCPD", + join_vars = exprs(AVALC, ADT), + join_type = "after", + first_cond_upper = AVALC.join == "iCPD", + condition = AVALC == "iUPD" & + all(AVALC.join %in% c("iCPD", "iUPD", "NE")), set_values_to = exprs(AVALC = "iCPD") ) + ibor_iupd <- event( description = "Define unconfirmed progressive disease (iUPD) for best overall response (iBOR)", dataset_name = "ovr", @@ -635,30 +655,30 @@ ibor_iupd <- event( ibor_ne <- event( description = paste( "Define not evaluable (NE) for best overall response (iBOR) as iSD, NON-iCR/NON-iUPD,", - "or NE (should be specified after ibor_isd and ibor_non_icripd)" + "or NE (should be specified after ibor_isd and ibor_non_icriupd)" ), dataset_name = "ovr", condition = AVALC %in% c("iSD", "NON-iCR/NON-iUPD", "NE"), set_values_to = exprs(AVALC = "NE") ) - adrs <- adrs %>% derive_extreme_event( by_vars = exprs(STUDYID, USUBJID), - order = exprs(ADT), + tmp_event_nr_var = event_nr, + order = exprs(event_nr,ADT), mode = "first", source_datasets = list( ovr = ovr, adsl = adsl ), - events = list(ibor_icr, ibor_ipr, ibor_isd, ibor_non_icripd, ibor_icpd, ibor_iupd, ibor_ne, no_data_missing), + events = list(ibor_icr, ibor_ipr, ibor_isd, ibor_non_icriupd, ibor_iupd, ibor_icpd, ibor_ne, no_data_missing), set_values_to = exprs( PARAMCD = "IBOR", PARAM = "Immune Best Overall Response by Investigator (confirmation not required)", PARCAT1 = "Tumor Response", PARCAT2 = "Investigator", - PARCAT3 = "iRecist", + PARCAT3 = "iRECIST", AVAL = aval_resp_new(AVALC), ANL01FL = "Y" ) @@ -681,12 +701,14 @@ different events. Some of the other functions from above can then be re-used passing in these confirmed response records. See the examples below of derived parameters requiring confirmation. The assessment and the confirmatory assessment here need to occur at least 28 days apart *(without any +1 applied to -this calculation of days between visits)*, using the `icrsp_y_cr`[^1], -`icrsp_y_ipr`[^2], `icbor_icr`[^3], and `icbor_ipr`[^4] event. +this calculation of days between visits)*, using the `icrsp_y_cr`, +`icrsp_y_ipr`, `icbor_icr`, and `icbor_ipr` event. Here the confirmation period +and the `keep_source_vars` argument is updated, as well as the `first_cond_upper` and +`condition` for the iRECIST values. -[^1]: -```{r} +```{r } confirmation_period <- 28 + icrsp_y_icr <- event_joined( description = paste( "Define confirmed response as iCR followed by iCR at least 28 days later and", @@ -696,17 +718,14 @@ icrsp_y_icr <- event_joined( join_vars = exprs(AVALC, ADT), join_type = "after", order = exprs(ADT), - first_cond = AVALC.join == "iCR" & + first_cond_upper = AVALC.join == "iCR" & ADT.join >= ADT + days(confirmation_period), condition = AVALC == "iCR" & all(AVALC.join %in% c("iCR", "NE")) & count_vals(var = AVALC.join, val = "NE") <= 1, set_values_to = exprs(AVALC = "Y") ) -``` -[^2]: -```{r} -confirmation_period <- 28 + icrsp_y_ipr <- event_joined( description = paste( "Define confirmed response as iPR followed by iCR or iPR at least 28 days later,", @@ -716,7 +735,7 @@ icrsp_y_ipr <- event_joined( join_vars = exprs(AVALC, ADT), join_type = "after", order = exprs(ADT), - first_cond = AVALC.join %in% c("iCR", "iPR") & + first_cond_upper = AVALC.join %in% c("iCR", "iPR") & ADT.join >= ADT + days(confirmation_period), condition = AVALC == "iPR" & all(AVALC.join %in% c("iCR", "iPR", "NE")) & @@ -731,10 +750,7 @@ icrsp_y_ipr <- event_joined( ), set_values_to = exprs(AVALC = "Y") ) -``` -[^3]: -```{r} -confirmation_period <- 28 + icbor_icr <- event_joined( description = paste( "Define complete response (iCR) for confirmed best overall response (iCBOR) as", @@ -743,17 +759,14 @@ icbor_icr <- event_joined( dataset_name = "ovr", join_vars = exprs(AVALC, ADT), join_type = "after", - first_cond = AVALC.join == "iCR" & + first_cond_upper = AVALC.join == "iCR" & ADT.join >= ADT + confirmation_period, condition = AVALC == "iCR" & all(AVALC.join %in% c("iCR", "NE")) & count_vals(var = AVALC.join, val = "NE") <= 1, set_values_to = exprs(AVALC = "iCR") ) -``` -[^4]: -```{r} -confirmation_period <- 28 + icbor_ipr <- event_joined( description = paste( "Define partial response (iPR) for confirmed best overall response (iCBOR) as", @@ -763,7 +776,7 @@ icbor_ipr <- event_joined( dataset_name = "ovr", join_vars = exprs(AVALC, ADT), join_type = "after", - first_cond = AVALC.join %in% c("iCR", "iPR") & + first_cond_upper = AVALC.join %in% c("iCR", "iPR") & ADT.join >= ADT + confirmation_period, condition = AVALC == "iPR" & all(AVALC.join %in% c("iCR", "iPR", "NE")) & @@ -783,8 +796,7 @@ icbor_ipr <- event_joined( Please note that the result `AVALC = "Y"` for confirmed clinical benefit is defined by the first _two_ events specified for `events`. For subjects with observations fulfilling both events the one with the earlier date should be -selected (and not the first one in the list). Thus `ignore_event_order = TRUE` -is specified. +selected (and not the first one in the list). ```{r} adrs <- adrs %>% @@ -797,13 +809,12 @@ adrs <- adrs %>% adsl = adsl ), events = list(icrsp_y_icr, icrsp_y_ipr, no_data_n), - ignore_event_order = TRUE, set_values_to = exprs( PARAMCD = "ICRSP", - PARAM = "Immune Response by Investigator (confirmation required)", + PARAM = "Immune Confirmed Response by Investigator", PARCAT1 = "Tumor Response", PARCAT2 = "Investigator", - PARCAT3 = "iRecist", + PARCAT3 = "iRECIST", AVAL = yn_to_numeric(AVALC), ANL01FL = "Y" ) @@ -819,13 +830,12 @@ adrs <- adrs %>% ovr = ovr, adsl = adsl ), - ignore_event_order = TRUE, set_values_to = exprs( PARAMCD = "ICCB", - PARAM = "Immune Clinical Benefit by Investigator (confirmation required)", + PARAM = "Immune Confirmed Clinical Benefit by Investigator", PARCAT1 = "Tumor Response", PARCAT2 = "Investigator", - PARCAT3 = "iRecist", + PARCAT3 = "iRECIST", AVAL = yn_to_numeric(AVALC), ANL01FL = "Y" ), @@ -835,19 +845,20 @@ adrs <- adrs %>% adrs <- adrs %>% derive_extreme_event( by_vars = exprs(STUDYID, USUBJID), - order = exprs(ADT), + tmp_event_nr_var = event_nr, + order = exprs(event_nr,ADT), mode = "first", - events = list(icbor_icr, icbor_ipr, ibor_isd, ibor_non_icripd, ibor_icpd, ibor_iupd, ibor_ne, no_data_missing), + events = list(icbor_icr, icbor_ipr, ibor_isd, ibor_non_icriupd, ibor_iupd, ibor_icpd, ibor_ne, no_data_missing), source_datasets = list( ovr = ovr, adsl = adsl ), set_values_to = exprs( PARAMCD = "ICBOR", - PARAM = "Immune Best Overall Response by Investigator (confirmation required)", + PARAM = "Immune Best Confirmed Overall Response by Investigator", PARCAT1 = "Tumor Response", PARCAT2 = "Investigator", - PARCAT3 = "iRecist", + PARCAT3 = "iRECIST", AVAL = aval_resp(AVALC), ANL01FL = "Y" ) From 169bcb67d95ea8cc81b559551f7cb5304795e84d Mon Sep 17 00:00:00 2001 From: Vinh Nguyen Date: Tue, 28 Nov 2023 10:01:17 -0500 Subject: [PATCH 04/14] 233 - iRECIST vignette - 2nd round comments --- vignettes/irecist.Rmd | 63 ++++++++++++++++++++++++++++--------------- 1 file changed, 41 insertions(+), 22 deletions(-) diff --git a/vignettes/irecist.Rmd b/vignettes/irecist.Rmd index ad42eae3..49be3ed5 100644 --- a/vignettes/irecist.Rmd +++ b/vignettes/irecist.Rmd @@ -220,9 +220,11 @@ dataset_vignette( ### Derive `AVALC` and `AVAL` Here we populate `AVALC` and create the numeric version as `AVAL` -(ordered from best to worst response). The `AVAL` values are not considered in +(ordered from worst to best response). The `AVAL` values are not considered in the parameter derivations below, and so changing `AVAL` here would not change -the result of those derivations. +the result of those derivations. However, please note that the ordering of `AVAL` +will be used to determine `ANL01FL` in the subsequent step, ensure that the appropriate +`mode` is being set in the `admiral::derive_var_extreme_flag()`. iRECIST ordering will be used or if you'd like to provide your own company-specific ordering here you could do this as follows: @@ -272,7 +274,7 @@ adrs <- adrs %>% by_vars = exprs(STUDYID, USUBJID, ADT), order = exprs(AVAL, RSSEQ), new_var = ANL01FL, - mode = "last" + mode = "first" ), filter = !is.na(AVAL) & AVALC !="MISSING" & ADT >= RANDDT ) @@ -406,7 +408,8 @@ records. For the parameter derivations, all values except those overwritten by `set_values_to` argument are kept from the earliest occurring input record fulfilling the required criteria. -When an `iCPD` occurs,the date would be that of the first `iUPD`. +When an iCPD occurs, the date of progression would be the same as +RECIST 1.1 date (i.e., first `iUPD` date in that block/bar). The function `admiral::derive_extreme_records()`, in conjunction with the event `icpd_y`, could be used to find the date of the first `iUPD`. @@ -426,7 +429,7 @@ adrs <- adrs %>% events = list(icpd_y, no_data_n), set_values_to = exprs( PARAMCD = "ICPD", - PARAM = "Immune Confirmation of Disease Progression by Investigator", + PARAM = "iRECIST Confirmation of Disease Progression by Investigator", PARCAT1 = "Tumor Response", PARCAT2 = "Investigator", PARCAT3 = "iRECIST", @@ -453,7 +456,7 @@ adrs <- adrs %>% events = list(iupd_y, no_data_n), set_values_to = exprs( PARAMCD = "IUPD", - PARAM = "Immune Unconfirmed Disease Progression by Investigator", + PARAM = "iRECIST Unconfirmed Disease Progression by Investigator", PARCAT1 = "Tumor Response", PARCAT2 = "Investigator", PARCAT3 = "iRECIST", @@ -505,7 +508,7 @@ adrs <- adrs %>% ), set_values_to = exprs( PARAMCD = "IRSP", - PARAM = "Immune Response by Investigator (confirmation not required)", + PARAM = "iRECIST Response by Investigator (confirmation not required)", PARCAT1 = "Tumor Response", PARCAT2 = "Investigator", PARCAT3 = "iRECIST", @@ -562,7 +565,7 @@ adrs <- adrs %>% ), set_values_to = exprs( PARAMCD = "ICB", - PARAM = "Immune Clinical Benefit by Investigator (confirmation for response not required)", + PARAM = "iRECIST Clinical Benefit by Investigator (confirmation for response not required)", PARCAT1 = "Tumor Response", PARCAT2 = "Investigator", PARCAT3 = "iRECIST", @@ -672,10 +675,10 @@ adrs <- adrs %>% ovr = ovr, adsl = adsl ), - events = list(ibor_icr, ibor_ipr, ibor_isd, ibor_non_icriupd, ibor_iupd, ibor_icpd, ibor_ne, no_data_missing), + events = list(ibor_icr, ibor_ipr, ibor_isd, ibor_non_icriupd, ibor_icpd, ibor_iupd, ibor_ne, no_data_missing), set_values_to = exprs( PARAMCD = "IBOR", - PARAM = "Immune Best Overall Response by Investigator (confirmation not required)", + PARAM = "iRECIST Best Overall Response by Investigator (confirmation not required)", PARCAT1 = "Tumor Response", PARCAT2 = "Investigator", PARCAT3 = "iRECIST", @@ -711,8 +714,9 @@ confirmation_period <- 28 icrsp_y_icr <- event_joined( description = paste( - "Define confirmed response as iCR followed by iCR at least 28 days later and", - "at most one NE in between" + "Define confirmed response as iCR followed by iCR at least", + confirmation_period, + "days later and at most one NE in between" ), dataset_name = "ovr", join_vars = exprs(AVALC, ADT), @@ -728,8 +732,9 @@ icrsp_y_icr <- event_joined( icrsp_y_ipr <- event_joined( description = paste( - "Define confirmed response as iPR followed by iCR or iPR at least 28 days later,", - "at most one NE in between, and no iPR after iCR" + "Define confirmed response as iPR followed by iCR or iPR at least", + confirmation_period, + "days later at most one NE in between, and no iPR after iCR" ), dataset_name = "ovr", join_vars = exprs(AVALC, ADT), @@ -754,7 +759,9 @@ icrsp_y_ipr <- event_joined( icbor_icr <- event_joined( description = paste( "Define complete response (iCR) for confirmed best overall response (iCBOR) as", - "iCR followed by iCR at least 28 days later and at most one NE in between" + "iCR followed by iCR at least", + confirmation_period, + "days later and at most one NE in between" ), dataset_name = "ovr", join_vars = exprs(AVALC, ADT), @@ -770,8 +777,9 @@ icbor_icr <- event_joined( icbor_ipr <- event_joined( description = paste( "Define partial response (iPR) for confirmed best overall response (iCBOR) as", - "iPR followed by iCR or iPR at least 28 days later, at most one NE in between,", - "and no iPR after iCR" + "iPR followed by iCR or iPR at least", + confirmation_period, + "days later, at most one NE in between and no iPR after iCR" ), dataset_name = "ovr", join_vars = exprs(AVALC, ADT), @@ -811,7 +819,7 @@ adrs <- adrs %>% events = list(icrsp_y_icr, icrsp_y_ipr, no_data_n), set_values_to = exprs( PARAMCD = "ICRSP", - PARAM = "Immune Confirmed Response by Investigator", + PARAM = "iRECIST Confirmed Response by Investigator", PARCAT1 = "Tumor Response", PARCAT2 = "Investigator", PARCAT3 = "iRECIST", @@ -832,7 +840,7 @@ adrs <- adrs %>% ), set_values_to = exprs( PARAMCD = "ICCB", - PARAM = "Immune Confirmed Clinical Benefit by Investigator", + PARAM = "iRECIST Confirmed Clinical Benefit by Investigator", PARCAT1 = "Tumor Response", PARCAT2 = "Investigator", PARCAT3 = "iRECIST", @@ -848,14 +856,14 @@ adrs <- adrs %>% tmp_event_nr_var = event_nr, order = exprs(event_nr,ADT), mode = "first", - events = list(icbor_icr, icbor_ipr, ibor_isd, ibor_non_icriupd, ibor_iupd, ibor_icpd, ibor_ne, no_data_missing), + events = list(icbor_icr, icbor_ipr, ibor_isd, ibor_non_icriupd, ibor_icpd, ibor_iupd, ibor_ne, no_data_missing), source_datasets = list( ovr = ovr, adsl = adsl ), set_values_to = exprs( PARAMCD = "ICBOR", - PARAM = "Immune Best Confirmed Overall Response by Investigator", + PARAM = "iRECIST Best Confirmed Overall Response by Investigator", PARCAT1 = "Tumor Response", PARCAT2 = "Investigator", PARCAT3 = "iRECIST", @@ -874,4 +882,15 @@ dataset_vignette( ``` ## Other Endpoints {#other} -For additional endpoints that can be added please see [Creating ADRS (Including Non-standard Endpoints)](adrs.html). +The following parameters may also be added: + +BCP - Best Overall Response of CR/PR by Investigator (confirmation not required)
+CBCP - Best Confirmed Overall Response of CR/PR by Investigator
+A1BOR - Best Overall Response by Investigator (confirmation not required) - Recist 1.1 adjusted for NED at Baseline
+ACCB - Alternative Confirmed Clinical Benefit by Investigator
+OVRB - Overall Response by BICR
+DEATH - Death
+LSTA - Last Disease Assessment by Investigator
+MDIS - Measurable Disease at Baseline by Investigator
%>% + +For examples on the additional endpoints, please see [Creating ADRS (Including Non-standard Endpoints)](adrs.html). From 9ffd0d7b8aa872cbb1b986fa30e1fb107901d8bf Mon Sep 17 00:00:00 2001 From: Stefan Bundfuss Date: Wed, 29 Nov 2023 10:25:33 +0000 Subject: [PATCH 05/14] #233 iRECIST_vignette_main: add handling of RECIST/iRECIST mixture --- vignettes/irecist.Rmd | 26 +++++++++++++++++++++++--- 1 file changed, 23 insertions(+), 3 deletions(-) diff --git a/vignettes/irecist.Rmd b/vignettes/irecist.Rmd index ad42eae3..dcab2c05 100644 --- a/vignettes/irecist.Rmd +++ b/vignettes/irecist.Rmd @@ -81,9 +81,13 @@ unless otherwise specified.* ## Read in Data {#readdata} -To start, all data frames needed for the creation of `ADRS` should be -read into the environment. This will be a company specific process. Some -of the data frames needed may be `ADSL`, `RS` and `TU`. +To start, all data frames needed for the creation of `ADRS` should be read into +the environment. This will be a company specific process. Some of the data +frames needed may be `ADSL`, `RS` and `TU`. For this vignette we assume that +`RS` provides the response values `"iCR"`, `"iPR"`, `"iSD"`, +`"NON-iCR/NON-iUPD"`, `"iUPD"`, `"iCP"`, and `"NE"`. All examples can be easily +modified to consider other response values (see [Handling Different Input +Response Values](#different_resp_vals)). For example purpose, the SDTM and ADaM datasets (based on CDISC Pilot test data)---which are included in `{pharmaversesdtm}` and `{pharmaverseadam}`---are used. @@ -398,6 +402,22 @@ no_data_missing <- event( ``` +### Handling Different Input Response Values {#different_resp_vals} +If `RS` contains other response values than the iRECIST responses, the `event()` +and `event_joined()` can be adjusted to cover this scenario. For example, if +RECIST responses (`"CR"`, `"PR"`, `"SD"`, ...) are collected up to first PD and +iRECIST responses (`"iCR"`, `"iPR"`, `"iSD"`, ...) thereafter, the `event()` +object defining unconfirmed response can be adjusted in the following way. +``` +irsp_y <- event( + description = "Define CR, iCR, PR, or iPR as (unconfirmed) response", + dataset_name = "ovr", + condition = AVALC %in% c("CR", "iCR", "PR", "iPR"), + set_values_to = exprs(AVALC = "Y") +) + +``` + ## Derive Confirmed and Unconfirmed Progressive Disease Parameter {#pd} Now that we have the input records prepared above with any From fee44c375ac16c73c4171b224ec3a5393bb2017d Mon Sep 17 00:00:00 2001 From: Stefan Bundfuss Date: Wed, 29 Nov 2023 10:59:21 +0000 Subject: [PATCH 06/14] #233 iRECIST_vignette_main: fix links --- .github/ISSUE_TEMPLATE/05_onboard.yml | 40 --------------------------- .github/pull_request_template.md | 12 ++++---- 2 files changed, 5 insertions(+), 47 deletions(-) delete mode 100644 .github/ISSUE_TEMPLATE/05_onboard.yml diff --git a/.github/ISSUE_TEMPLATE/05_onboard.yml b/.github/ISSUE_TEMPLATE/05_onboard.yml deleted file mode 100644 index 9f6897a0..00000000 --- a/.github/ISSUE_TEMPLATE/05_onboard.yml +++ /dev/null @@ -1,40 +0,0 @@ -name: Onboarding Tasks -description: Bringing a Core or non-Core member onto the admiral team [for admiral team only] -title: "Onboarding: " -labels: ["onboarding"] -assignees: - - octocat -body: - - type: markdown - attributes: - value: | - Welcome to the Team! We love contributors! - - type: checkboxes - id: core - attributes: - label: Onboarding tasks for Core (Roche-GSK) Team Members - description: - options: - - label: Given a tour of Github from a Core member - - label: Understand how to Create Issues and do a Pull Request - - label: Understand the Programming Strategy - - label: Read and understand [Developer Guides Articles](https://pharmaverse.github.io/admiraldev/devel/articles/index.html) - - label: Invited to all relevant meetings - Stand Ups, Retrospective, Sprint Planning, Question/Comments, Backlog, Community Meeting - - label: Given access to Box and relevant documents - - label: Given write access to Github Repository - - label: Slack channel invites to admiral and admiralonco_dev - - label: Introduction to Teams ways of working - - type: checkboxes - id: non-core - attributes: - label: Onboarding tasks for non-Core Team Members - description: - options: - - label: Given a tour of Github from a Core member - - label: Understand how to Create Issues and do a Pull Request - - label: Understand the Programming Strategy - - label: Read and understand [Developer Guides Articles](https://pharmaverse.github.io/admiraldev/devel/articles/index.html) - - label: Invited to all relevant meetings - Question/Comments, Community Meeting - - label: Given write access to Github Repository - - label: Slack channel invites to admiral - - label: Introduction to Teams ways of working diff --git a/.github/pull_request_template.md b/.github/pull_request_template.md index 7564ba9d..90dbadf3 100644 --- a/.github/pull_request_template.md +++ b/.github/pull_request_template.md @@ -1,13 +1,11 @@ -Please add "Closes #" to the title of the pull request. Then the -issue is closed automatically once it is merged to `main`. +Thank you for your Pull Request! We have developed this task checklist from the [Development Process Guide](https://pharmaverse.github.io/admiraldev/articles/development_process.html) to help with the final steps of the process. Completing the below tasks helps to ensure our reviewers can maximize their time on your code as well as making sure the admiral codebase remains robust and consistent. -Thank you for your Pull Request! We have developed this task checklist from the [Development Process Guide](https://pharmaverse.github.io/admiraldev/main/articles/development_process.html) to help with the final steps of the process. Completing the below tasks helps to ensure our reviewers can maximize their time on your code as well as making sure the admiral codebase remains robust and consistent. - -Please check off each taskbox as an acknowledgment that you completed the task or check off that it is not relevant to your Pull Request. This checklist is part of the Github Action workflows and the Pull Request will not be merged into the `devel` branch until you have checked off each task. +Please check off each taskbox as an acknowledgment that you completed the task or check off that it is not relevant to your Pull Request. This checklist is part of the Github Action workflows and the Pull Request will not be merged into the `main` branch until you have checked off each task. +- [ ] Place Closes # into the beginning of your Pull Request Title (Use Edit button in top-right if you need to update). Then the issue is closed automatically once it is merged to `main`. - [ ] Code is formatted according to the [tidyverse style guide](https://style.tidyverse.org/). Run `styler::style_file()` to style R and Rmd files -- [ ] Updated relevant unit tests or have written new unit tests - See [Unit Test Guide](https://pharmaverse.github.io/admiraldev/main/articles/unit_test_guidance.html#writing-unit-tests-in-admiral) -- [ ] If you removed/replaced any function and/or function parameters, did you fully follow the [deprecation guidance](https://pharmaverse.github.io/admiraldev/main/articles/programming_strategy.html#deprecation)? +- [ ] Updated relevant unit tests or have written new unit tests - See [Unit Test Guide](https://pharmaverse.github.io/admiraldev/articles/unit_test_guidance.html#writing-unit-tests-in-admiral) +- [ ] If you removed/replaced any function and/or function parameters, did you fully follow the [deprecation guidance](https://pharmaverse.github.io/admiraldev/articles/programming_strategy.html#deprecation)? - [ ] Update to all relevant roxygen headers and examples - [ ] Run `devtools::document()` so all `.Rd` files in the `man` folder and the `NAMESPACE` file in the project root are updated appropriately - [ ] Address any updates needed for vignettes and/or templates From 4e15d527df1147f808b20a86ce9cf63f4e6e304d Mon Sep 17 00:00:00 2001 From: Stefan Bundfuss Date: Wed, 29 Nov 2023 11:05:02 +0000 Subject: [PATCH 07/14] #233 iRECIST_vignette_main: fix spelling --- inst/WORDLIST | 6 ++++++ vignettes/irecist.Rmd | 6 +++--- 2 files changed, 9 insertions(+), 3 deletions(-) diff --git a/inst/WORDLIST b/inst/WORDLIST index 20951a07..1f0971bb 100644 --- a/inst/WORDLIST +++ b/inst/WORDLIST @@ -1,12 +1,15 @@ +ACCB ADRS ADSL ADTR ADTTE ADaM ADaMs +BCP BICR BOR Biologics +CBCP CDISC CRF GlaxoSmithKline @@ -14,7 +17,9 @@ Hoffmann IMWG IRF LLC +LSTA Myeloma +OVRB PFS Pre RECIST @@ -31,6 +36,7 @@ evaluable fil fmt funder +iCPD iRECIST myeloma pharmaverse diff --git a/vignettes/irecist.Rmd b/vignettes/irecist.Rmd index 8079d995..5514f4ef 100644 --- a/vignettes/irecist.Rmd +++ b/vignettes/irecist.Rmd @@ -352,7 +352,7 @@ dataset_vignette( The building blocks for the events that contribute to deriving common endpoints like what constitutes a responder, or a Best Overall Response of complete -response (CR), ... are predefined in admiralonco for Recist 1.1 (see [Pre-Defined +response (CR), ... are predefined in admiralonco for RECIST 1.1 (see [Pre-Defined Response Event Objects](../reference/event_objects.html)). New Response Event Objects are needed for iRECIST and any study-specific needs. @@ -906,11 +906,11 @@ The following parameters may also be added: BCP - Best Overall Response of CR/PR by Investigator (confirmation not required)
CBCP - Best Confirmed Overall Response of CR/PR by Investigator
-A1BOR - Best Overall Response by Investigator (confirmation not required) - Recist 1.1 adjusted for NED at Baseline
+A1BOR - Best Overall Response by Investigator (confirmation not required) - RECIST 1.1 adjusted for NED at Baseline
ACCB - Alternative Confirmed Clinical Benefit by Investigator
OVRB - Overall Response by BICR
DEATH - Death
LSTA - Last Disease Assessment by Investigator
-MDIS - Measurable Disease at Baseline by Investigator
%>% +MDIS - Measurable Disease at Baseline by Investigator For examples on the additional endpoints, please see [Creating ADRS (Including Non-standard Endpoints)](adrs.html). From ff65905ab26350b07ec4c03df461e28f96a77e98 Mon Sep 17 00:00:00 2001 From: Stefan Bundfuss Date: Wed, 29 Nov 2023 11:08:15 +0000 Subject: [PATCH 08/14] #233 iRECIST_vignette_main: style files --- vignettes/irecist.Rmd | 17 ++++++++--------- 1 file changed, 8 insertions(+), 9 deletions(-) diff --git a/vignettes/irecist.Rmd b/vignettes/irecist.Rmd index 5514f4ef..04954c0f 100644 --- a/vignettes/irecist.Rmd +++ b/vignettes/irecist.Rmd @@ -280,7 +280,7 @@ adrs <- adrs %>% new_var = ANL01FL, mode = "first" ), - filter = !is.na(AVAL) & AVALC !="MISSING" & ADT >= RANDDT + filter = !is.na(AVAL) & AVALC != "MISSING" & ADT >= RANDDT ) ``` @@ -367,7 +367,7 @@ icpd_y <- event_joined( join_type = "after", first_cond_upper = AVALC.join == "iCPD", condition = AVALC == "iUPD" & - all(AVALC.join %in% c("iCPD", "iUPD", "NE" )), + all(AVALC.join %in% c("iCPD", "iUPD", "NE")), set_values_to = exprs(AVALC = "Y") ) @@ -401,7 +401,6 @@ no_data_missing <- event( set_values_to = exprs(AVALC = "MISSING"), keep_source_vars = adsl_vars ) - ``` ### Handling Different Input Response Values {#different_resp_vals} @@ -461,7 +460,7 @@ adrs <- adrs %>% ovr_orig <- ovr ovr <- ovr %>% group_by(USUBJID) %>% - filter(ADT >= max_cond(var = ADT, cond = AVALC == "iUPD")) %>% + filter(ADT >= max_cond(var = ADT, cond = AVALC == "iUPD")) %>% ungroup(USUBJID) adrs <- adrs %>% @@ -689,13 +688,13 @@ adrs <- adrs %>% derive_extreme_event( by_vars = exprs(STUDYID, USUBJID), tmp_event_nr_var = event_nr, - order = exprs(event_nr,ADT), + order = exprs(event_nr, ADT), mode = "first", source_datasets = list( ovr = ovr, adsl = adsl ), - events = list(ibor_icr, ibor_ipr, ibor_isd, ibor_non_icriupd, ibor_icpd, ibor_iupd, ibor_ne, no_data_missing), + events = list(ibor_icr, ibor_ipr, ibor_isd, ibor_non_icriupd, ibor_icpd, ibor_iupd, ibor_ne, no_data_missing), set_values_to = exprs( PARAMCD = "IBOR", PARAM = "iRECIST Best Overall Response by Investigator (confirmation not required)", @@ -735,7 +734,7 @@ confirmation_period <- 28 icrsp_y_icr <- event_joined( description = paste( "Define confirmed response as iCR followed by iCR at least", - confirmation_period, + confirmation_period, "days later and at most one NE in between" ), dataset_name = "ovr", @@ -780,7 +779,7 @@ icbor_icr <- event_joined( description = paste( "Define complete response (iCR) for confirmed best overall response (iCBOR) as", "iCR followed by iCR at least", - confirmation_period, + confirmation_period, "days later and at most one NE in between" ), dataset_name = "ovr", @@ -874,7 +873,7 @@ adrs <- adrs %>% derive_extreme_event( by_vars = exprs(STUDYID, USUBJID), tmp_event_nr_var = event_nr, - order = exprs(event_nr,ADT), + order = exprs(event_nr, ADT), mode = "first", events = list(icbor_icr, icbor_ipr, ibor_isd, ibor_non_icriupd, ibor_icpd, ibor_iupd, ibor_ne, no_data_missing), source_datasets = list( From 48ee1bb288d8cd1f9946dbb8f89fafef13a7047a Mon Sep 17 00:00:00 2001 From: Stefan Bundfuss Date: Tue, 5 Dec 2023 14:28:56 +0000 Subject: [PATCH 09/14] #233 iRECIST_vignette_main: fix typos --- vignettes/irecist.Rmd | 19 +++++++++---------- 1 file changed, 9 insertions(+), 10 deletions(-) diff --git a/vignettes/irecist.Rmd b/vignettes/irecist.Rmd index 04954c0f..d081eca0 100644 --- a/vignettes/irecist.Rmd +++ b/vignettes/irecist.Rmd @@ -85,7 +85,7 @@ To start, all data frames needed for the creation of `ADRS` should be read into the environment. This will be a company specific process. Some of the data frames needed may be `ADSL`, `RS` and `TU`. For this vignette we assume that `RS` provides the response values `"iCR"`, `"iPR"`, `"iSD"`, -`"NON-iCR/NON-iUPD"`, `"iUPD"`, `"iCP"`, and `"NE"`. All examples can be easily +`"NON-iCR/NON-iUPD"`, `"iUPD"`, `"iCPD"`, and `"NE"`. All examples can be easily modified to consider other response values (see [Handling Different Input Response Values](#different_resp_vals)). @@ -150,15 +150,14 @@ Independent Review Facility (IRF)/Blinded Independent Central Review (BICR) records). It could even involve merging input data from other sources besides `RS`, such as `ADTR`. -This step would include any required selection/derivation of `ADT` or -applying any necessary partial date imputations, updating `AVAL` (e.g. -this should be ordered from best to worst response), and setting -analysis flag `ANL01FL`. Common options for `ANL01FL` would be to set -null for invalid assessments or those occurring after new anti-cancer -therapy, or to only flag assessments on or after after date of first -treatment/randomization, or rules to cover the case when a patient has -multiple observations per visit (e.g. by selecting worst value). Another -consideration could be extra potential protocol-specific sources of +This step would include any required selection/derivation of `ADT` or applying +any necessary partial date imputations, updating `AVAL` (e.g. this should be +ordered from best to worst response), and setting analysis flag `ANL01FL`. +Common options for `ANL01FL` would be to set null for invalid assessments or +those occurring after new anti-cancer therapy, or to only flag assessments on or +after date of first treatment/randomization, or rules to cover the case when a +patient has multiple observations per visit (e.g. by selecting the worst value). +Another consideration could be extra potential protocol-specific sources of Progressive Disease such as radiological assessments, which could be pre-processed here to create a PD record to feed downstream derivations. From 83d4e66bf40d36877564f9d6f7dfdc4b88c0f54d Mon Sep 17 00:00:00 2001 From: Vinh Nguyen Date: Wed, 6 Dec 2023 13:07:56 -0500 Subject: [PATCH 10/14] #233 - iRECIST vignette - 3rd round comment update. --- _pkgdown.yml | 4 ++-- vignettes/irecist.Rmd | 20 ++++++++++---------- 2 files changed, 12 insertions(+), 12 deletions(-) diff --git a/_pkgdown.yml b/_pkgdown.yml index 01123833..af54376b 100644 --- a/_pkgdown.yml +++ b/_pkgdown.yml @@ -72,14 +72,14 @@ navbar: href: articles/adrs_basic.html - text: Creating ADRS (Including Non-standard Endpoints) href: articles/adrs.html + - text: Creating ADRS with iRECIST endpoints + href: articles/irecist.html - text: Creating ADTTE href: articles/adtte.html - text: Creating ADTR href: articles/adtr.html - text: Creating and Using New Anti-Cancer Start Date href: articles/nactdt.html - - text: Creating ADRS with iRECIST endpoints - href: articles/irecist.html slack: icon: fa-slack href: https://app.slack.com/client/T028PB489D3/C02M8KN8269 diff --git a/vignettes/irecist.Rmd b/vignettes/irecist.Rmd index d081eca0..e0ac5bc7 100644 --- a/vignettes/irecist.Rmd +++ b/vignettes/irecist.Rmd @@ -426,8 +426,11 @@ records. For the parameter derivations, all values except those overwritten by `set_values_to` argument are kept from the earliest occurring input record fulfilling the required criteria. -When an iCPD occurs, the date of progression would be the same as -RECIST 1.1 date (i.e., first `iUPD` date in that block/bar). +When an `iCPD` occurs, the date of progression would be the first occurrence of `iUPD` in that block. +For example, when we have values of `iUPD`, `iUPD`, and `iCPD`, the iRECIST `PD` date would +be the first occurrence of `iUPD`. In cases where we have `SD`, `SD`, `iUPD`, `PR`, `PR`, `iUPD`, and `iCPD`, +the iRECIST `PD` date would be the second occurrence of `iUPD`. + The function `admiral::derive_extreme_records()`, in conjunction with the event `icpd_y`, could be used to find the date of the first `iUPD`. @@ -902,13 +905,10 @@ dataset_vignette( The following parameters may also be added: -BCP - Best Overall Response of CR/PR by Investigator (confirmation not required)
-CBCP - Best Confirmed Overall Response of CR/PR by Investigator
-A1BOR - Best Overall Response by Investigator (confirmation not required) - RECIST 1.1 adjusted for NED at Baseline
-ACCB - Alternative Confirmed Clinical Benefit by Investigator
-OVRB - Overall Response by BICR
-DEATH - Death
-LSTA - Last Disease Assessment by Investigator
-MDIS - Measurable Disease at Baseline by Investigator +IBCP - iRECIST Best Overall Response of CR/PR by Investigator (confirmation not required)
+ICBCP - iRECIST Best Confirmed Overall Response of CR/PR by Investigator
+IOVRB - iRECIST Overall Response by BICR
+ILSTA - iRECIST Last Disease Assessment by Investigator
+IMDIS - iRECIST Measurable Disease at Baseline by Investigator For examples on the additional endpoints, please see [Creating ADRS (Including Non-standard Endpoints)](adrs.html). From 4eddbec6890630e416408e0ef2bc8a0a813fae2d Mon Sep 17 00:00:00 2001 From: Vinh Nguyen Date: Fri, 8 Dec 2023 09:59:21 -0500 Subject: [PATCH 11/14] 233 - updated sort for AVAL --- vignettes/irecist.Rmd | 18 +++++++++--------- 1 file changed, 9 insertions(+), 9 deletions(-) diff --git a/vignettes/irecist.Rmd b/vignettes/irecist.Rmd index e0ac5bc7..605c4738 100644 --- a/vignettes/irecist.Rmd +++ b/vignettes/irecist.Rmd @@ -223,7 +223,7 @@ dataset_vignette( ### Derive `AVALC` and `AVAL` Here we populate `AVALC` and create the numeric version as `AVAL` -(ordered from worst to best response). The `AVAL` values are not considered in +(ordered from worst to best response, followed by `NE` and MISSING). The `AVAL` values are not considered in the parameter derivations below, and so changing `AVAL` here would not change the result of those derivations. However, please note that the ordering of `AVAL` will be used to determine `ANL01FL` in the subsequent step, ensure that the appropriate @@ -235,14 +235,14 @@ could do this as follows: ```{r} aval_resp_new <- function(arg) { case_when( - arg == "iCR" ~ 8, - arg == "iPR" ~ 7, - arg == "iSD" ~ 6, - arg == "NON-iCR/NON-iUPD" ~ 5, - arg == "iUPD" ~ 4, - arg == "iCPD" ~ 3, - arg == "NE" ~ 2, - arg == "MISSING" ~ 1, + arg == "NE" ~ 8, + arg == "MISSING" ~ 7, + arg == "iCR" ~ 6, + arg == "iPR" ~ 5, + arg == "iSD" ~ 4, + arg == "NON-iCR/NON-iUPD" ~ 3, + arg == "iUPD" ~ 2, + arg == "iCPD" ~ 1, TRUE ~ NA_real_ ) } From 070e05868ebf937577654e08cbd2fb5f0d31a7d5 Mon Sep 17 00:00:00 2001 From: Stefan Bundfuss Date: Tue, 12 Dec 2023 15:53:23 +0000 Subject: [PATCH 12/14] #233 iRECIST_vignette_main: add changelog item --- NEWS.md | 4 ++++ 1 file changed, 4 insertions(+) diff --git a/NEWS.md b/NEWS.md index 94bb5da0..1041e9e1 100644 --- a/NEWS.md +++ b/NEWS.md @@ -1,5 +1,9 @@ # admiralonco (development version) +## Documentation + +- New vignette "Creating ADRS with iRECIST endpoints". (#233) + ## Various - Website now has button/links to Slack channel and GitHub Issues. (#262) From cd2b86e9afff17c9e7d2d90572398db54b64c68f Mon Sep 17 00:00:00 2001 From: Stefan Bundfuss Date: Tue, 12 Dec 2023 15:58:46 +0000 Subject: [PATCH 13/14] #233 iRECIST_vignette_main: clean up Changelog --- NEWS.md | 10 ++++------ 1 file changed, 4 insertions(+), 6 deletions(-) diff --git a/NEWS.md b/NEWS.md index 0853fb03..4e4ec105 100644 --- a/NEWS.md +++ b/NEWS.md @@ -4,12 +4,6 @@ - New vignette "Creating ADRS with iRECIST endpoints". (#233) -## Various - -- Website now has button/links to Slack channel and GitHub Issues. (#262) - -## Documentation - - All vignettes and templates were updated to be in line with the changes in `{admiral}` (see [Breaking Changes](https://pharmaverse.github.io/admiral/news/index.html#breaking-changes-1-0-0) @@ -27,6 +21,10 @@ won't be deprecated in the near future. (#256) - The function `call_aval_fun()`, which was deprecated in admiralonco 0.4.0, has been removed. (#256) +## Various + +- Website now has button/links to Slack channel and GitHub Issues. (#262) + # admiralonco 0.5.0 ## New Features From 27194637b592d1bec87c79264a707016d2e7c6da Mon Sep 17 00:00:00 2001 From: Stefan Bundfuss Date: Wed, 13 Dec 2023 12:11:20 +0000 Subject: [PATCH 14/14] #233 iRECIST_vignette_main: fix links --- vignettes/irecist.Rmd | 30 ------------------------------ 1 file changed, 30 deletions(-) diff --git a/vignettes/irecist.Rmd b/vignettes/irecist.Rmd index 605c4738..75a3a92e 100644 --- a/vignettes/irecist.Rmd +++ b/vignettes/irecist.Rmd @@ -14,36 +14,6 @@ knitr::opts_chunk$set( comment = "#>" ) -library(admiral) - -link <- function(text, url) { - return( - paste0( - "[", text, "]", - "(", url, ")" - ) - ) -} -dyn_link <- function(text, - base_url, - relative_url = "", - # Change to TRUE when admiral adopts multiversion docs - is_multiversion = FALSE, - multiversion_default_ref = "main") { - url <- paste(base_url, relative_url, sep = "/") - if (is_multiversion) { - url <- paste( - base_url, - Sys.getenv("BRANCH_NAME", multiversion_default_ref), - relative_url, - sep = "/" - ) - } - return(link(text, url)) -} -# Other variables -admiral_homepage <- "https://pharmaverse.github.io/admiral/cran-release" - library(admiraldev) ```