Classic rxode2 Events
2024-04-23
Source:vignettes/rxode2-events-classic.Rmd
rxode2-events-classic.RmdClassic RxODE evid values
Originally RxODE supported compound event IDs; rxode2 still supports these parameters, but it is often more useful to use the the normal NONMEM dataset standard that is used by many modeling tools like NONMEM, Monolix and nlmixr, described in the rxode2 types article.
Classically, RxODE supported event coding in a single event id
evid described in the following table.
| 100+ cmt | Infusion/Event Flag | <99 Cmt | SS flag & Turning off Compartment |
|---|---|---|---|
| 100+ cmt | 0 = bolus dose | < 99 cmt | 01 = dose |
| 1 = infusion (rate) | 08 = Turn off Steady state infusion with lag time | ||
| 2 = infusion (dur) | 09 = Steady state 1 at dose time with alag (SS=1) | ||
| 6 = turn off modeled duration | 10 = Steady state 1 (equivalent to SS=1) without alag() | ||
| 7 = turn off modeled rate | 09 = Steady state 1/2 at dose+ alag() | ||
| 8 = turn on modeled duration | 19 = Steady state 2 at dose time with alag (SS=2) | ||
| 9 = turn on modeled rate | 20 = Steady state 2 (equivalent to SS=2) | ||
| 4 = replace event | 30 = Turn off a compartment (equivalent to -CMT w/EVID=2) | ||
| 5 = multiply event | 40 = Steady state constant infusion | ||
| 50 = Phantom event, used for transit compartments doses | |||
| 60 = Non-tracking dose, a dose that is not counted for time after dose and related numbers. Used for turning on compartments |
The classic EVID concatenate the numbers in the above table, so an
infusion would to compartment 1 would be 10101 and an
infusion to compartment 199 would be 119901.
EVID = 0 (observations), EVID=2 (other type event) and EVID=3 are all supported. Internally an EVID=9 is a non-observation event and makes sure the system is initialized to zero; EVID=9 should not be manually set. EVID 10-99 represents modeled time interventions, similar to NONMEM’s MTIME. This along with amount (amt) and time columns specify the events in the ODE system.
For infusions specified with EVIDs > 100 the amt column represents the rate value.
For Infusion flags 1 and 2 +amt turn on the infusion to
a specific compartment -amt turn off the infusion to a
specific compartment. To specify a dose/duration you place the dosing
records at the time the duration starts or stops.
For modeled rate/duration infusion flags the on infusion flag must be followed by an off infusion record.
These number are concatenated together to form a full RxODE event ID, as shown in the following examples:
Bolus Dose Examples
A 100 bolus dose to compartment #1 at time 0
| time | evid | amt |
|---|---|---|
| 0 | 101 | 100 |
| 0.5 | 0 | 0 |
| 1 | 0 | 0 |
A 100 bolus dose to compartment #99 at time 0
| time | evid | amt |
|---|---|---|
| 0 | 9901 | 100 |
| 0.5 | 0 | 0 |
| 1 | 0 | 0 |
A 100 bolus dose to compartment #199 at time 0
| time | evid | amt |
|---|---|---|
| 0 | 109901 | 100 |
| 0.5 | 0 | 0 |
| 1 | 0 | 0 |
Infusion Event Examples
Bolus infusion with rate 50 to compartment 1 for 1.5 hr, (modeled bioavailability changes duration of infusion)
| time | evid | amt |
|---|---|---|
| 0 | 10101 | 50 |
| 0.5 | 0 | 0 |
| 1 | 0 | 0 |
| 1.5 | 10101 | -50 |
Bolus infusion with rate 50 to compartment 1 for 1.5 hr (modeled bioavailability changes rate of infusion)
| time | evid | amt |
|---|---|---|
| 0 | 20101 | 50 |
| 0.5 | 0 | 0 |
| 1 | 0 | 0 |
| 1.5 | 20101 | -50 |
Modeled rate with amount of 50
| time | evid | amt |
|---|---|---|
| 0 | 90101 | 50 |
| 0 | 70101 | 50 |
| 0.5 | 0 | 0 |
| 1 | 0 | 0 |
Modeled duration with amount of 50
| time | evid | amt |
|---|---|---|
| 0 | 80101 | 50 |
| 0 | 60101 | 50 |
| 0.5 | 0 | 0 |
| 1 | 0 | 0 |
Steady State for classic RxODE EVID example
Steady state dose to cmt 1
| time | evid | amt | ii |
|---|---|---|---|
| 0 | 110 | 50 | 24 |
Steady State with super-positioning principle for am 50 and pm 100 dose
| time | evid | amt | ii |
|---|---|---|---|
| 0 | 110 | 50 | 24 |
| 12 | 120 | 100 | 24 |
Steady state with lagged dose for classic RxODE evid
Steady state with lagged dose for a bolus dose:
0 | 109 | 100 | 24 |
0 | 101 | 100 | 0 |
The event 109 calculates the trough amount after the steady state has
passed by (ii-lag_time) while event 101 applies the next
steady state dose.
Steady state (=2) with a lagged bolus dose
| time | evid | amt | ii |
|---|---|---|---|
| 0 | 109 | 50 | 24 |
| 0 | 101 | 50 | |
| 12 | 119 | 100 | 24 |
| 12 | 101 | 100 |
Steady state infusion with lag time
0 | 10109 | 5 | 24 |
0 | 10108 | -5 | 24 |
0 | 10101 | 5 | |
20 | 10101 | -5 | |
As in the case of the bolus, the 10109 event calculates
the trough concentration with ii=24, which may (or may not)
still have an infusion running. If the infusion is running the
10108 event will turn off that infusion at the appropriate
time. If the infusion has been completed, then the 10108
event is ignored.
The next 2 events 10101 represent the event times
(assuming no bioavailability has been applied).
Turning off a compartment with classic RxODE EVID
Turn off the first compartment at time 12
| time | evid | amt |
|---|---|---|
| 0 | 110 | 50 |
Event coding in rxode2 is encoded in a single event
number evid. For compartments under 100, this is coded
as:
- This event is
0for observation events. - For a specified compartment a bolus dose is defined as:
- 100*(Compartment Number) + 1
- The dose is then captured in the
amt
- For IV bolus doses the event is defined as:
- 10000 + 100*(Compartment Number) + 1
- The infusion rate is captured in the
amtcolumn - The infusion is turned off by subtracting
amtwith the sameevidat the stop of the infusion.
For compartments greater or equal to 100, the 100s place and above
digits are transferred to the 100,000th place digit. For doses to the
99th compartment the evid for a bolus dose would be
9901 and the evid for an infusion would be
19901. For a bolus dose to the 199th
compartment the evid for the bolus dose would be
109901. An infusion dosing record for the
199th compartment would be 119901.