Translating your dataset from NONMEM format to the MonolixSuite format

The required format for the data set in NONMEM and in the Monolix Suite is very similar. Usually only few changes (if any) are required to go from one format to the other one.

 

General formatting

  • Column names: in the Monolix Suite column names are not restricted in length, and not restricted to uppercase format. Yet, only alphanumeric and the underscore “_” characters are allowed. Special characters such as spaces ” “, stars “*”, parenthèses or brackets “(“, dashes “-“, slashes “/” are not supported.
  • Header line: no need to start the header line with the “#” character in the Monolix Suite, the column headers line will be recognized automatically.
  • Number of columns: there is no limitation of the number of columns in the Monolix Suite

Dose column-types

  • SS column: SS=2 and SS=3 are not supported in the Monolix Suite. When a data set contains a column with column-type SS, there must be a column with column-type II. If SS=1, then the value in the II column must be strictly positive. In case of steady-state, steady-state formulas are not used. Instead, additional doses (5 by default) are added before the SS dose to reach steady-state.
  • RATE and TINF: in case of an infusion, in the Monolix Suite, it is possible to define either the rate (RATE column-type) or the duration (TINF column-type). The rate and the duration are related to each other via the amount: TINF=RATE/AMT. Negative values in the RATE column-type result in a bolus, when used in combination with the iv macro (and models from the library with iv). When used in combination with the oral macro (and models from the library with oral0 or oral1), the RATE column is ignored if the value is negative and an error is triggered if the value is positive. If infusion duration is defined in the model (parameter or fixed value), the RATE column is not necessary (in opposition to NONMEM, where RATE=-1 and RATE=-2 are used).
  • CMT column: in NONMEM, for observation-lines, CMT specifies the compartment from which the predicted value of the observation is obtained. For dose-lines, CMT specifies the compartment into which the dose is introduced. In the MonolixSuite, the matching between the data (dose and observation lines) and the model (administrations and predictions) is done using identifiers, not based on compartment numbers. To assign a dose to a specific administration of the model (oral or iv macros for classical PK models, depot macro for more complex ODEs), the column ADM is used. The identifier in the ADM column should match the “type=” field of the macro. To assign an observation to a prediction, the column YTYPE is used. Observation lines with YTYPE=1 will be assigned to the first output (output = {…} statement in the model file), lines with YTYPE=2 to the second output, etc. Note that the default values for the administration type in administration macros or in the pkmodel macro is type=1. Similarly, in case of a single output, YTYPE=1 by default (while in NONMEM, the central compartment may have number 1 or 2). In the ADM column-type, negative values are not allowed. Turning off compartments should instead be defined in the model file.

Control and event columns-types

  • EVID column-type: in the Monolix Suite, the EVID column is not mandatory, since dose-events (EVID=1) and response-events (EVID=0) are automatically recognized. Note that the Monolix Suite does not recognize EVID=2 (“Other event”) and EVID=3 (“Reset event”), but recognizes EVID=4 (which corresponds to a reset to initial values immediately followed by a dose). EVID=4 creates a new occasion for the individual. In NONMEM, EVID=2 is sometimes used to define a time point at which one would like to predict a concentration, without having an observation. In the Monolix Suite, this is done using MDV=2 (see below).
  • MDV column-type: the MDV column is not mandatory in the Monolix Suite. Dose-lines and observation-lines will be recognized automatically. Yet the MDV column can be useful to force a response-line to be ignored (MDV=1). Several MDV columns are allowed, in this case a synthetic MDV value is computed. In the Monolix Suite, MDV can in addition take the value MDV=2, which permits to define a time point (and possibly a regressor value) to output a prediction without having the corresponding observation. In Monolix, the time points tagged MDV=2 will for instance appear in the table “fulltimes.txt”, outputted when selecting “All times” in the “Outputs to save” window.

Response column-types

  • Censored data: in the Monolix Suite, censored data should be tagged in the data set using additional columns with CENS (mark as censored observation) and if necessary LIMIT (give other interval boundary) column-types. The LOQ value is indicated in the Y column. Censored data are then automatically taken into account in the likelihood in a rigorous statistical way. If only the CENS column is used, the method in the MonolisSuite is equivalent to the so-called M3 method. When both CENS and LIMIT are used, the method in equivalent to M4.

Subject identification columns-types

  • ID column-type: in NONMEM all lines related to a single individual must be in one block, which is not the case in the Monolix Suite. If the ID column contains the following IDs: [1,1,1,2,2,1,1], NONMEM will consider that the dataset comprise three individuals with IDs 1 (with 3 observations), 2 (with 2 observations) and 1_1 (with 2 observations). In the Monolix Suite, two individuals are considered, with IDs 1 (with 5 observations) and 2 (with 2 observations).

Time column-types

  • TIME column-type: values in the time column can be negative in the Monolix Suite.

Covariates and regression column-types

  • Covariates: in the Monolix Suite, columns corresponding to continuous covariates must be set to the COV column-type, and categorical covariates to the CAT column-type
  • Regression variables: in the Monolix Suite, regression variables must be set to the X column-type. If several regression variables are used, their order must be the same in the dataset and in the “input” field of the model file.

Unsupported column-types

  • The PCMT, CONT, CALL, MRG_, RAW_, RPT_, L1, and L2 column-types are not supported in the MonolixSuite.