Classic rxode2 Events

2023-03-21

Classic 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 of Compartment
100+ cmt	0 = bolus dose	< 99 cmt	1 = dose
	1 = infusion (rate)		10 = Steady state 1 (equivalent to SS=1)
	2 = infusion (dur)		20 = Steady state 2 (equivalent to SS=2)
	6 = turn off modeled duration		30 = Turn off a compartment (equivalent to -CMT w/EVID=2)
	7 = turn off modeled rate
	8 = turn on modeled duration
	9 = turn on modeled rate
	4 = replace event
	5 = multiply event

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
0	110	50

Steady State with super-positioning principle for am 50 and pm 100 dose

time	evid	amt
0	110	50
12	120	100

Turning off a compartment with classic RxODE EVID

Turn off the first compartment at time 12

time	evid	amt
0	110	50
12	130	NA

Event coding in rxode2 is encoded in a single event number evid. For compartments under 100, this is coded as:

• This event is 0 for 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 amt column
  • The infusion is turned off by subtracting amt with the same evid at 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.