Treatments definition includes times and amounts of the doses applied to the model. Treatments are applied to the model via the macros depot(), iv() or oral() used in the model. Moreover, treatments definition has an administration id, which allows to choose to which macros used in the model the doses are applied.
When used in “Exploration” or “Simulation“, several treatment elements can be combined together. For instance, a loading dose of type manual followed by maintenance doses of type regular, or a oral dose with adm=2 and an iv dose with adm=1.
The units of time and amounts must be consistent with the units of the Monolix data set or with the model definition when starting from scratch.
Demo projects: 3.1. treatments
New treatments element
Several types of elements can be defined:
- Regular: It is used for regularly spaced dosing times with a unique amount and a unique infusion duration or rate (optional). It requires the start time, inter-dose internal, number of doses, and amount.
- Manual: It is a vector that has one or several dosing times with identical or different amounts. The + and – buttons allow to add and remove doses.
- External: An external text file with columns id (optional), occasions (optional), time (mandatory), amount (mandatory), tinf or rate (optional), washout (optional). The occasions headers must correspond to the occasion names defined in the occasion element. When id and occasion columns are present, then they must be the first columns. When the id column is not present, the treatment is considered ‘common’, i.e the same for all individuals. The washout column can contain zeros (no washout) or ones (washout).
The external file can be tab, comma or semicolon separated. The possible file extensions are .csv or .txt.
Additional treatments definition specifications:
- adm: [all] the administration id of the treatment element (integer). The doses of a treatment element with adm=2 apply to all model macros defined with adm=2, for instance
oral(adm=2, ka). Macros used in the model without adm are implicitly defined with adm=1.
- infusion duration or rate: [regular/manual] the list button on the right allows to display the infusion column. The value is understood as either a duration or a rate, depending on the chosen option.
- washout: [manual] the list button on the right allows to display the washout column. When the washout tick-box is selected, a washout is applied just before the dose. A washout means that all model variables are reset to their initial values.
- repeat: [regular/manual] This option allows to repeat a base pattern of doses several times (number of repetitions), with a given periodicity (cycle duration). In the example below, the dose is given on the three first days of the week, for 4 weeks. The doses on the first week are defined using the type ‘regular’ with three doses and an inter-dose interval of 1 day. This base pattern is then repeated every 7 days (cycle duration), 3 times (number of repetitions) in addition to the first week.
- scale amount by a covariate: [regular/manual] This option allows to personalize the dose given to different individuals by scaling the dose amount with the selected covariate and with a specific intercept for the linear relationship: \(\text{Scaled amount} = \text{Amount} \times \text{Selected covariate} + \text{Intercept}\).
- non-compliance probability: [all] The doses defined are applied to the model with a given probability (1-p) , where p is the probability to miss a dose. This allows to simulate non-adherence to a treatment. Which doses are applied and which are not rely on the random number seed defined in the project settings to ensure reproducibility.
Treatment elements imported from Monolix
Importing a Monolix project generates automatically a treatment element for each administration id defined in the Monolix data set.
- mlx_AdmX: contains treatment information for admID=X for each individual including: dosing times, amount, infusion duration or rates (optional) and washouts (optional, from EVID=3 or EVID=4 in Monolix). The Monolix data set column SS is replaced by additional dose lines as defined by the Monolix setting “number of steady-state doses”. The ADDL column is also replaced by additional dose lines.
