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# NCA settings

The following page describes all the settings for the parameters calculations.

### Calculations

These settings corresponds to the settings impacting the calculation of the NCA parameters.

• Administration type: Intravenous or Extravascular. This defines the drug type of administration. IV bolus and IV infusions must be set as “intravenous”.
• Integral method: Method for AUC and AUMC calculation and interpolation. Trapezoidal refers to formula to calculate the AUC and Interpolation refers to the formula to add an additional point in case of partial AUC with a time point not originally present in the data set. See the Calculation rules for details on the formulas.
• Linear Trapezoidal Linear (Linear trapezoidal, linear interpolation): For AUC calculation linear formula. For interpolation linear formula.
• Linear Log Trapezoidal (Linear/log trapezoidal, linear/log interpolation): For AUC, linear before Cmax and log after Cmax. For interpolation, linear before Cmax and log after.
• Linear Up Log Down (LinUpLogDown trapezoidal, LinUpLogDown interpolation): For AUC, linear if concentration is going up or is stable, log if going down. For interpolation, linear if concentration is going up or is stable, log if going down.
• Linear Trapezoidal linear/log (Linear trapezoidal, linear/log interpolation): For AUC, linear formula. For interpolation, linear before Cmax, log after Cmax. If several Cmax, the first one is used.

For all methods, if an observation value is less than or equal to zero, the program defaults to the linear trapezoidal or interpolation rule for that point. Similarly, if adjacent observations values are equal to each other, the program defaults to the linear trapezoidal or interpolation rule.

• Partial AUC time: Define if the user would like to compute a partial AUC in a specific time interval. It is possible to define several partial AUC intervals, applicable to all individuals.
• BLQ before Tmax: In case of BLQ measurements, this corresponds to the method by which the BLQ data before Tmax should be replaced. Possible methods are “missing”, “LOQ”, “LOQ/2” or “0” (default value is 0).
• BLQ after Tmax: In case of BLQ measurements, this corresponds to the method by which the BLQ data after Tmax should be replaced. Possible methods are “missing”, “LOQ”, “LOQ/2” or “0” (default value is LOQ/2).

### Settings impacting the $$\lambda_z$$ calculation

This settings are impacting the calculation of $$\lambda_z$$. See also the Check lambda_z page.

• Main rule for the $$\lambda_z$$ estimation. It corresponds to the rule to define the measurements used for the $$\lambda_Z$$ calculation. Possible rules are “R2”, “interval”, “points” or “adjustedR2” (called Best Fit in Winonlin) (default value is “adjustedR2”). See the calculation rules for more details.
• In case of “R2” or “adjustedR2” rule, the user has the possibility to define the maximum number of points and/or minimum time for the $$\lambda_z$$ estimation. It allows to constrain the points tested for inclusion.
• In case of “Interval” rule, the user has the possibility to define the time interval to consider.
• In case of “Points” rule, the user has the possibility to define the number of points to consider.
• Weighting method used for the regression that estimates $$\lambda_z$$. Possible methods are “Y”, “Y2” or “uniform” (default value is “uniform”).

### Selecting NCA parameters to compute

The NCA parameters to compute can be selected from the “Parameter” column to be placed in the “Computed parameters” column, either by clicking on one or several parameters and using the arrows, or by double clicking on the parameters.

It is recommended to always compute Rsq_adjusted, No_points_lambda_z, Lambda_z and Lambda_z_intercept as these parameters are necessary to display the terminal slope and information box in the NCA fit plot.

The list of parameters computed by default when starting a new PKanalix project can be defined in the Settings > Preferences.

### Acceptance criteria

These settings corresponds to the settings impacting the acceptance criteria. When acceptance criteria are defined, flags indicating if the condition is met or not are added to the output result table. Statistics in the summary table can be calculated using only individuals who satisfy one or several acceptance criteria. The filtering option is available directly in the Summary sub-tab of the NCA results.

• Adjusted R2: It corresponds to the threshold of the adjusted R2 for the estimation of $$\lambda_z$$. If activated, it will fill the value of Flag_Rsq_adjusted: if Rsq_adjusted > threshold, then Flag_Rsq_adjusted=1. The default value is .98.
• % extrapolated AUC: It corresponds to the threshold of the percentage of the total predicted AUC (or AURC for urine models) due to the extrapolation to infinity after the last measurement. If activated, it will fill the value of Flag_AUC_%Extrap_pred: if AUC_%Extrap_pred < threshold, then Flag_AUC_%Extrap_pred=1. The default value is 20%.
• Span: It corresponds to the threshold of the span. The span corresponds to the ratio of the sampling interval length for the $$\lambda_z$$ calculation and the half-life. If activated, it will fill the value of Flag_Span: if Span > threshold, then Flag_Span=1. The default value is 3.

### Global

• Obs. ID to use: when a column OBSERVATION ID has defined several types of measurements in the data set, this setting permit to choose which one to use for the NCA analysis