Chapter 11 Multi-instrument variables

11.1 Date and time variables

As dates and times are used across instruments to capture delays between an event and another (e.g. between index cardiotoxicity and death), there are attributed a specific naming scheme:

  • They do not start by the instrument identifier

  • They have their own identifier date for dates and ti for times.

  • Time variables always have 3 components:

    • The ti identifier

    • The first event identifier

    • The second event identifier

There is an exception to this naming rule: time between 2 cures of ICI (either previous line or current line), which has the long suffix regimen_freq.

For example, time between index cardiotoxicity and death is ti_ic_death. An event identifier can have a middle _ if its very long (e.g. cl1stctla4_other for current line first dose of an unspecified anti-CTLA4, although this is quite a rare case.

Time variables represent delays between two dates.

Of note, times can be expressed in days, weeks or years.

var instrument unit quick desc
ti_tobaccoquit_ic demo years From tobacco quitting to IC
ti_otx_ic demo years From organ transplant x to IC
ti_plicistop_ic demo days From previous line ICI stop (end of regimen) to IC
pl_drug_regimen_freq previous_line weeks From one cure to another, during an ICI therapy regimen
ti_ic_1ststeroid ic days From IC to first dose of steroids
ti_cl1stnivo_ic cl days From current line ICI-drug 1st infusion to IC
ti_ic_ihdischarge ih days Length of hospital stay

11.2 Time to cardiotoxicity onset from immune checkpoint inhibitor introduction

As the title suggests, the idea is to collect the time to onset between the first dose of immune checkpoint inhibitor received during the current cycle and the occurrence of cardiotoxicity.

This data is stored at the immune checkpoint inhibitor level, e.g., a patient who received nivolumab will have this data stored in a nivolumab specific variable. The structure for this data is

Var name Description
ti_cl1stdrug_ic It is a delay, in days. Drug name is abbreviated to a 4 digit name
ti_cl1stdrug_ic__c Same but computed from dates (when available).
ti_cl1stdrug_ic__old It is an old variable which has now the \@ HIDDEN status, and is similar to ti_cl1stdrug_ic__c

To capture this time to onset, you have to check every possibilities for a patient, e.g. you must check for all immune checkpoint inhibitor level time variables and choose which of these 3 variables you keep first, if ever more than one is available. This gives a quite heavy piece of code

ti_cl1stici_ic = expr(pmax( # pmax here: maximum delay (in the case multiple ICI were prescribed sequentially)

    eval(tto_uni_3v(ti_cl1statez_ic__c, ti_cl1statez_ic, ti_cl1statez_ic__old)), 
    eval(tto_uni_3v(ti_cl1stavel_ic__c, ti_cl1stavel_ic, ti_cl1stavel_ic__old)), 
    eval(tto_uni_3v(ti_cl1stcemi_ic__c, ti_cl1stcemi_ic, ti_cl1stcemi_ic__old)), 
    eval(tto_uni_3v(ti_cl1stdurv_ic__c, ti_cl1stdurv_ic, ti_cl1stdurv_ic__old)), 
    eval(tto_uni_3v(ti_cl1stipil_ic__c, ti_cl1stipil_ic, ti_cl1stipil_ic__old)), 
    eval(tto_uni_3v(ti_cl1stnivo_ic__c, ti_cl1stnivo_ic, ti_cl1stnivo_ic__old)), 
    eval(tto_uni_3v(ti_cl1stpemb_ic__c, ti_cl1stpemb_ic, ti_cl1stpemb_ic__old)), 
    eval(tto_uni_3v(ti_cl1sttrem_ic__c, ti_cl1sttrem_ic, ti_cl1sttrem_ic__old)), 
    eval(tto_uni_3v(ti_cl1stpd1_other_ic__c, ti_cl1stpd1_other_ic, 
        ti_cl1stpdl1_other_ic, ti_cl1stpdl1_other_ic__old)), 
    eval(tto_uni_3v(ti_cl1stctla4_other_ic__c, ti_cl1stctla4_other_ic, 
    na.rm = TRUE)

Where eval(tto_univ_3v()) would be a prioritizer function among the 3 variables. Note that we might want to substract the ti_icsy_ic delay, if we’re interested in the beginning of symptoms rather than index cardiotoxicity date.

tto_uni_3v <- # A 3 variables time to onset unifier !
  function( # used to organize the three variables of time to cardiotox onset from drug initiation
    ti_icistart_event__c, # all quasi quoted names of columns from data. One is the calculated delay `ti_icistart_event__c`, one is manually entered when dates are not available `ti_icistart_event`, one is a old version of the variable `ti_icistart_event__old`
    ti_icistart_event__c <- enexpr(ti_icistart_event__c)
    ti_icistart_event <- enexpr(ti_icistart_event)
    ti_icistart_event__old <- enexpr(ti_icistart_event__old)
    # underlying logic: 
    # first, prioritize calculated over manual vars with numvar_uni (intermediate object uni).
    # second, take the longest delay of uni and __old, if both are available.
    # third, if only one available, keep it (via na.rm = TRUE in pmax)
    # generate an expression to call numvar_uni
    uni <- numvar_uni(!!ti_icistart_event__c,
    ex <- quo(pmax(
      na.rm = TRUE)

numvar_uni <- # Numeric variables unifier
  function( # used to organize data entered from 2 variables, currently its a prioritization
    var1, # all quasi quoted names of columns from data. usually, one is the calculated var, one is manually entered, var1 will be prioritize over var2
    # underlying data.frame data argument is omitted
    var1 <- enexpr(var1)
    var2 <- enexpr(var2)
    ex <- expr(case_when(
      !!!var1) ~ as.numeric(!!var1),
      !!!var2) ~ as.numeric(!!var2),
      TRUE ~ NA_real_

11.3 Death

  • ih_ou_death : During index hospitalization

  • fu_death : During follow-up (later than discharge)