Drug description file specification¶

This section describes formal specifications of the Tucuxi Drug Description file (.tdd). Specifically it lists formal specifications of the various fields. Each specification is a unique number, prefixed by DFS (for Drug File Specification).

The drug model importer shall implement these verifications, and shall reference the DFS numbers in the comments.

The drug file editor shall implement these verifications, and shall reference the DFS numbers in the comments.

Model¶

The global structure of the XML file is the following:

Tag name	Format	Occ.	Description
<history>	History	1:1	History of the file
<head>	Head	1:1	General information
<drugModel>	DrugModel	1:1	Everything needed for computation

DFS-0001

A model shall have exactly one history, one head and one drugModel.

History¶

The history of the file is described inside the <history> tag. A standard history looks like this:

<history>
  <revisions>
    <revision>
      <revisionAction>creation</revisionAction>
      <revisionAuthorName>John Doe</revisionAuthorName>
      <institution>Name of his institution</institution>
      <email>john@doe.com</email>
      <date>2014-07-17</date>
      <comments/>
    </revision>
    <revision>
      <revisionAction>modification</revisionAction>
      <revisionAuthorName>Jane Doe</revisionAuthorName>
      <institution>Name of her institution</institution>
      <email>jane@doe.com</email>
      <date>2014-07-30</date>
      <comments/>
    </revision>
  </revisions>
</history>

Tag name	Format	Occ.	Description
<revisions>		1:1	List of revisions
___<revision>		1:∞	Revision
________<revisionAction>	string	1:1	Type of revision
________<revisionAuthorName>	string	1:1	Name of the person who wrote the revision
________<institution>	string	1:1	Name of institution from which the revision was written
________<email>	string	1:1	Email of the person who wrote the revision
________<date>	date	1:1	Date of the revision
________<comments>	Comments	1:1	Comments about the modifications done in this revision

DFS-0002

The type of revision is one of the following possibilities:

creation
modification
review
validation

DFS-0003

In a revisions list, there shall be at least one revision with revisionAction equal to creation.

DFS-0004

A revision shall contain exactly one revisionAction, one revisionAuthorName, one institution, one email, one date, and one comments.

DFS-0005

An email shall contain a valid email address, with an @ in it.

Head¶

The head of the file contains general information about the drug, such as its ID, the model it uses, its name, description and so on. It does not embed information required by the computing engines.

head content¶
Tag name	Format	Occ.	Description
<drug>		1:1	Description of the drug itself
___<atcs>		1:1	List of ATCs
______<atc>	string	1:∞	The drug code, or Anatomical Therapeutic Chemical (ATC)
___<activeSubstances>		1:1	List of active substances
______<activeSubstance>	string	1:∞	An active substance present in the drug
___<drugName>		1:1	The translated drug’s names
______<name>	string	1:∞	Name of the drug for the specified language
___<drugDescriptions>		1:1	The translated drug’s descriptions
______<desc>	string	1:∞	Description of the drug for the specified language
___<tdmStrategy>		1:1	The translated drug’s TDM strategy
______<text>	string	1:∞	TB : The description of the TDM strategy
<study>		1:1	Description of the study used to fill this file
___<studyName>		1:1	The translated drug’s study names
______<name>	string	1:∞	Study name of the drug for the specified language
___<studyAuthors>	string	1:1	The name of the study authors
___<description>		1:1	The translated descriptions of the study
______<desc>	string	1:∞	Description of the study for the specified language
___<references>		1:1	References to related publications
______<reference>	string	0:∞	Reference to a specific article or publication
<comments>	Comments	1:1	Comments about the drug’s header

DFS-0006

A head shall contain exactly one drug, one study and one comments.

DFS-0007

A drug shall contain exactly one atcs, one activeSubstances, one drugName, one drugDescriptions and one tdmStrategy.

DFS-0008

In drug, the list atcs shall contain at least one atc.

DFS-0009

In drug, an atc shall be a non empty string corresponding to a valid ATC format.

DFS-0010

In drug, the list activeSubstances shall contain at least one activeSubstance.

DFS-0011

In drug, an activeSubstance shall be a non empty string.

DFS-0012

In drug, the list drugName shall contain at least one name.

DFS-0013

In drug, the list drugDescriptions shall contain at least one desc.

DFS-0014

In drug, the list tdmStrategy shall contain at least one text.

DFS-0015

A study shall contain exactly one studyName, one studyAuthors, one description and one references.

DFS-0016

In study, an studyAuthors shall be a non empty string.

DFS-0017

In study, an studyName shall contain at least one name.

DFS-0018

A description follows the rules of a translatedDescs. It shall contain at least one desc, and only desc tags.

DFS-0019

In study, a reference shall have an attribute type that can be any of the following values:

plain
bibtex
doi

Drug model¶

The drug model embeds all information required for the various computations.

drugModel content¶
Tag name	Format	Occ.	Description
<drugModel>			Everything needed for any calculation
____<drugId>	string	1:1	Unique identifier of the drug
____<drugModelId>	string	1:1	Identifier of the model described in the file
____<domain>	Domain	1:1	Usage domain for this model. TB
____<covariates>	Covariates	1:1	List of covariates used by the model
____<activeMoieties>	ActiveMoieties	1:1	List of active moieties. TB
____<analyteGroups>	Analyte groups	1:1	List of groups of analytes
____<formulationAndRoutes>	Formulation and route	1:1	List of formulation and routes of administration
____<timeConsiderations>	Time considerations	1:1	Some information about time, such as halflife
____<comments>	Comments	1:1	General comments on the model

DFS-0020

A drug model shall contain exactly one drugId, one drugModelId, one domain, one covariates, one activeMoieties, one analyteGroups, one formulationAndRoutes, one timeConsiderations, and one comments.

DFS-0021

A drugId shall be a non empty string.

DFS-0022

A drugModelId shall be a non empty string.

Domain¶

domain content¶
Tag name	Format	Occ.	Description
<description>		1:1	The translated descriptions of the domain
___<desc>	string	1:∞	Description of the domain for the specified language
<constraints>	string	1:1	List of constraints allowing the model to be used
___<constraint>	Constraint	0:∞	A constraint for using the model
______<constraintType>	ConstraintType	1:1	Importance of the constraint: soft or hard
______<errorMessage>		1:1	The translated error message for the constraint
_________<text>	string	1:∞	Error message in the specified language
______<requiredCovariates>		1:1	List of required covariates for checking this constraint
_________<covariateId>	string	1:∞	Id of a covariate required by this constraint
______<checkOperation>	Operation	1:1	formula used to check the validity of covariates
______<comments>	Comments	1:1	Comments conserning the constraint

DFS-0023

A domain shall contain exactly one description and one constraints.

DFS-0024

A constraint shall contain exactly one constraintType, one errorMessage, one requiredCovariates, one checkOperation, and one comments.

DFS-0025

A constraintType is any of the following:

soft
hard

DFS-0026

An errorMessage shall contain at least one text.

DFS-0027

A requiredCovariates shall contain at least one covariateId.

DFS-0028

A covariateId found in a requiredCovariates list shall exist as a covariateId in a covariate.

DFS-0029

A checkOperation is an operation, and shall be validated as an operation.

Operation¶

An operation is used at many places within the file, with different tags refering to it.

DFS-0030

An operation shall contain one of the following:

softFormula
hardFormula
multiFormula

and a comments.

DFS-0031

A softFormula shall contain one inputs and one code.

DFS-0032

An inputs shall contain any number of input.

DFS-0033

An input shall contain one id and one type.

DFS-0034

In an input, an id shall reference an existing covariateId present in a covariate.

DFS-0035

In an input, a type is any of the following:

int
double
bool

DFS-0036

A hardFormula contains a single identifier, from a predefined list:

To be defined

DFS-0037

A multiFormula contains at least one softFormula or hardFormula. It can then contain any number of these items, in any order.

Covariate¶

A covariate represents an information about the patient that can be useful for computations.

covariates content¶
Tag name	Format	Occ.	Description
<covariate>		0:∞	Description of a covariate
____<covariateId>	string	1:1	The covariate’s unique identifier
____<covariateName>		1:1	The translated covariate’s names
_______<name>	string	1:∞	Name of the covariate for the specified language
____<description>		1:1	The translated covariate’s descriptions
_______<desc>	string	1:∞	Description of the covariate for the specified language
____<unit>	string	1:1	The covariate’s unit
____<covariateType>	covariateType	1:1	The covariate’s type
____<dataType>	covariateDataType	1:1	The covariate’s type
____<interpolationType>	interpolationType	1:1	The covariate’s type
____<refreshPeriod>		0:1	The refresh period for the covariate value
________<unit>		1:1	The unit of the refresh period
________<value>		1:1	The duration of the refresh period
____<covariateValue>	stdAprioriValue	1:1	The covariate’s value, that can be modified by other covariates
____<validation>	ref:validation	1:1	Potential validation function for the covariate value
____<comments>	Comments	1:1	Comments about the covariate

DFS-0038

A covariates shall contain any number of covariate, but only covariate tags.

DFS-0039

A covariate shall contain exactly one covariateId, one covariateName, one description, one unit, one covariateType, one dataType, one interpolationType, one covariateValue, one validation and one comments.

DFS-0040

A covariateId, in a covariate, shall be an non-empty string.

DFS-0041

A covariateName follows the rules of a translatedNames.

DFS-0043

In a covariate, a unit is any valid unit, as described in Unit.

DFS-0044

In a covariate, if the covariateType is a sex, then the unit shall be empty or -.

If the covariateType is ageInYears, then the unit shall be y.

If the covariateType is ageInMonths, then the unit shall be mon.

If the covariateType is ageInWeeks, then the unit shall be w.

If the covariateType is ageInDays, then the unit shall be d.

If the covariateType is dose, then the unit shall be a valid Weight unit.

DFS-0045

In a covariate, if the covariateId is bodyweight, then the unit shall be a Weight unit.

If the covariateId is temperature, then the unit shall be a Temperature unit.

TODO : Add validations for known covariateIds.

DFS-0046

A dataType is any of the following:

int
double
bool

DFS-0047

A covariateType is any of the following:

standard
sex
ageInYears
ageInMonths
ageInWeeks
ageInDays
dose

DFS-0048

A interpolationType is any of the following:

direct
linear

Two other values are valid, but not yet supported by the software.

DFS-0049

In a covariate, if interpolationType is not direct, then there should be a refreshPeriod in covariate.

DFS-0050

A refreshPeriod shall contain one unit and one value.

DFS-0051

In a refreshPeriod, the unit shall be a valid Time unit.

DFS-0052

In a refreshPeriod, the value shall be a valid strictly positive floating point number.

DFS-0053

A validation tag shall contain an errorMessage, an operation, and a comments.

Active moiety¶

An active moiety corresponds to an active substance of the medical drug. A drug model can be composed of more than one active moiety, but this case is not very common. The activeMoietyId uniquely identifies the active moiety. In case of a single analyte drug model it is usually convenient to share the same Id as the analyte.

activeMoiety content¶
Tag name	Format	Occ.	Description
<activeMoiety>			An active moiety
____<activeMoietyid>	string	1:1	active moiety unique identifier
____<activeMoietyName>		1:1	The translated active moiety’s names
_______<name>	string	1:∞	Name of the active moiety for the specified language
____<unit>	string	1:1	The active moiety’s unit
____<analyteIdList>		1:1	The list of analytes influencing this active moiety
_______<analyteId>	string	1:∞	The Id of an analyte required to compute this active moiety
____<analytesToMoietyFormula>	Operation	1:1	The formula for calculating the active moiety concentration based on the analytes
____<targets>	Targets	1:1	A list of targets
________<target>	Targets	0:∞	A target to be reached

DFS-0055

An activeMoieties shall contain at least one activeMoiety, and only activeMoiety tags.

DFS-0056

An activeMoiety shall contain one activeMoietyId, one activeMoietyName, one unit, one analyteIdList, one analytesToMoietyFormula, and one targets.

DFS-0057

An activeMoietyId shall be a non-empty string.

DFS-0058

An activeMoietyName is a translatedNames.

DFS-0059

In an activeMoiety the unit shall be a valid Concentration unit.

DFS-0060

An analyteIdList shall contain at least one analyteId, and only analyteId tags.

DFS-0061

In an analyteIdList, an analyteId shall be a non-empty string.

DFS-0062

An analytesToMoietyFormula is an operation.

Target¶

The targets of an active moiety are described in the <target> tag. It contains all the data about the targeted residual concentration, peak concentration and mean concentration.

target content¶
Tag name	Format	Occ.	Description
<target>			A target
____<targetType>	TargetType	1:1	Type of target, from an enumeration
____<targetValues>		1:1	The target values
________<unit>	string	1:1	The target unit
________<min>	stdAprioriValue	1:1	Minimum targeted value
________<max>	stdAprioriValue	1:1	Maximum targeted value
________<best>	stdAprioriValue	1:1	Best targeted value
________<toxicityAlarm>	stdAprioriValue	1:1	Threshold over which an alarm shall be triggered
________<inefficacyAlarm>	stdAprioriValue	1:1	Threshold under which an alarm shall be triggered
________<mic>		0:1	The MIC value, optional
____________<unit>	string	1:1	The MIC unit
____________<micValue>	stdAprioriValue	1:1	The MIC value
____<times>		0:1	Time targets when required by the target type
________<unit>	string	1:1	The time unit
________<min>	stdAprioriValue	1:1	Minimum targeted time
________<max>	stdAprioriValue	1:1	Maximum targeted time
________<best>	stdAprioriValue	1:1	Best targeted time
____<comments>	Comments	1:1	Comments about the target

DFS-0063

A targets shall only contain target tags.

DFS-0064

A target shall contain one targetType, one targetValues, 0 or 1 times (depending on the target type), and one comments.

If targetType is peak or peakDividedByMic, times is mandatory. Else it should not be present.

DFS-0065

A targetType shall be any of the following:

peak
residual
mean
auc
auc24
cumulativeAuc
aucOverMic
auc24OverMic
timeOverMic
aucDividedByMic
auc24DividedByMic
peakDividedByMic
residualDividedByMic
fractionTimeOverMic

DFS-0066

A targetValues shall contain one unit, one max, one min, one best, one toxicityAlarm, one inefficacyAlarm, and 0 or 1 mic, depending on the target type.

If targetType is aucOverMic, auc24OverMic, timeOverMic, aucDividedByMic, auc24DividedByMic, peakDividedByMic, residualDividedByMic, or fractionTimeOverMic mic is mandatory. Else it should not be present.

DFS-0067

In a target, if the targetType is peak, residual, mean, then the unit shall be a valid Concentration unit.

In a target, if the targetType is auc, auc24, cumulativeAuc, aucOverMic, auc24OverMic, then the unit shall be a valid Concentration Time unit.

In a target, if the targetType is timeOverMic, aucDividedByMic, then the unit shall be a valid Time unit.

In a target, if the targetType is peakDividedByMic, residualDividedByMic, or fractionTimeOverMic, then the unit shall be empty or “-“.

DFS-0068

A min is a stdAprioriValue.

DFS-0069

A max is a stdAprioriValue.

DFS-0070

A best is a stdAprioriValue.

DFS-0071

A toxicityAlarm is a stdAprioriValue.

DFS-0072

A inefficacyAlarm is a stdAprioriValue.

DFS-0160

In a targetValues, the default value of inefficacyAlarm shall be smaller of equal to the default value of min.

DFS-0161

In a targetValues, the default value of toxicityAlarm shall be greater or equal to the default value of max.

DFS-0154

In a targetValues, the default value of min shall be less or equal to the default value of best, the default value of best shall be less or equal to the default value of max.

DFS-0155

In a times, the default value of min shall be less or equal to the default value of best, the default value of best shall be less or equal to the default value of max.

DFS-0073

A times shall contain one unit, one min, one max, and one best.

DFS-0074

In a times, the unit shall be a valid Time unit.

Analyte group¶

analyteGroups content¶
Tag name	Format	Occ.	Description
<analyteGroups>		0:∞	List of groups of analytes
____<analyteGroup>	string	1:∞	A group a analytes
________<groupId>	string	1:1	A unique Id for the group of analytes
________<pkModelId>	string	1:1	The Id of the Pk Model to be used for computation related to this group
________<analytes>		1:1	The list of analytes of the group
____________<analyte>	Analyte	1:∞	An analyte
________<dispositionParameters>	ParameterSet	1:1	A set of disposition parameters
____________<parameters>		1:1	List of parameters
________________<parameter>	Parameter	1:∞	A disposition parameter
____________<correlations>	Correlations	1:1	correlation between disposition parameters

DFS-0075

An analytGroups shall contain at least one analyteGroup, and only analyteGroup tags.

DFS-0076

An analytGroup shall contain one groupId, one pkModelId, on analytes, and one dispositionParameters.

DFS-0077

An groupId shall be a non-empty string.

DFS-0078

A pkModelId identifies the PK model, and shall be one of the following (this list has to be updated when new models are added to Tucuxi):

“linear.1comp.macro”
“linear.1comp.micro”
“linear.2comp.macro”
“linear.2comp.macroRatios”
“linear.2comp.micro”
“linear.3comp.macro”
“linear.3comp.micro”
“linear.2comp.erlang1.macro”
“linear.2comp.erlang1.micro”
“linear.2comp.erlang2.macro”
“linear.2comp.erlang2.micro”
“linear.2comp.erlang3.macro”
“linear.2comp.erlang3.micro”
“linear.2comp.erlang4.macro”
“linear.2comp.erlang4.micro”
“linear.2comp.erlang5.macro”
“linear.2comp.erlang5.micro”
“linear.2comp.erlang6.macro”
“linear.2comp.erlang6.micro”
“michaelismenten.enzyme.1comp”

DFS-0079

A dispositionParameters is a parameterSet.

Analyte¶

analyte content¶
Tag name	Format	Occ.	Description
<analyte>			An analyte
____<analyteId>	string	1:1	The Id of the analyte
____<unit>	string	1:1	The unit used to do calculation with the analyte
____<molarMass>	string	1:1	The molar mass of the analyte
________<value>		1:1	Value of the molar mass
________<unit>	Analyte	1:∞	Unit of the molar mass
____<description>		1:1	The translated descriptions of the analyte
________<desc>	string	1:∞	Description of the analyte
____<errorModel>	Error model	1:1	The error model corresponding to this analyte
____<comments>	Comments	1:1	Comments about this analyte

DFS-0080

An analytes shall contain at least one analyte, and only analyte tags.

DFS-0081

An analyte shall contain one analyteId, one unit, one molarMass, one description, one errorModel, and one comments.

DFS-0082

In an analyte, the unit shall be a valid Concentration unit.

DFS-0083

A molarMass shall contain one value and one unit.

DFS-0084

In a molarMass, the value shall be a valid positive floating point number.

DFS-0085

In a molarMass, the unit shall be a Molar mass.

DFS-0086

In an analyte, an analyteId shall contain a non-empty string. This string shall be a valid analyteId defined in an activeMoiety.

DFS-0158

All analytes and active moieties have to share the same concentration unit. This constraint may be removed in a later version, but currently it has to be met.

Error model¶

errorModel content¶
Tag name	Format	Occ.	Description
<errorModel>			Some time considerations
____<errorModelType>	errorModelType	1:1	Type of error model, an enum
____<sigmas>		1:1	A list of sigmas
________<sigma>	stdAprioriValue	1:∞	A sigma used by the error model
____<comments>	Comments	1:1	Comments about the error model

DFS-0087

An errorModel shall contain one errorModelType, one sigmas and one comments.

DFS-0088

An errorModelType shall be any of the following:

additive
proportional
exponential
mixed
propexp
none

DFS-0089

In an errorModel, if the errorModelType is none, then sigmas shall be empty. If the errorModelType is mixed, then sigmas shall contain two sigma. If the errorModelType is additive, proportional, exponential or propexp, then sigmas shall contain one sigma.

DFS-0090

A sigma shall be a a stdAprioriValue with a default positive value.

Formulation and routes¶

formulationAndRoute content¶
Tag name	Format	Occ.	Description
<formulationAndRoute>			Formulation and route
____<formulationAndRouteId>	string	1:1	Id of the formulation and route
____<formulation>	string	1:1	the formulation. Taken from a dictionary
____<administrationName>	string	1:1	A free field to discriminate vendors
____<administrationRoute>	string	1:1	The route of administration, taken from a dictionary
____<absorptionModel>	absorptionModel	1:1	Id of the absorption model
____<dosages>	Dosages	1:1	Possible dosages
____<absorptionParameters>		1:1	Sets of absorption parameters
________<parameterSetAnalyteGroup>		0:∞	A set of absorption parameters for an analyte group
____________<analyteGroupId>	string	1:1	Id of the analyte group
____________<absorptionModel>	string	1:1	Id of the absorption model
____________<parameterSet>	ParameterSet	1:1	The absorption parameters

DFS-0091

A formulationAndRoutes shall contain at least one formulationAndRoute, and only formulationAndRoute tags.

DFS-0092

A formulationAndRoute shall contain one formulationAndRouteId, one formulation, one administrationName, one administrationRoute, one absorptionModel, one dosages, one absorptionParameters.

DFS-0093

A formulationAndRouteId shall be a non-empty string.

DFS-0094

A formulation shall be any of the following:

undefined
parenteralSolution
oralSolution
test

DFS-0095

An administrationName is any string.

DFS-0096

An administrationRoute shall be any of the following:

undefined
intramuscular
intravenousBolus
intravenousDrip
nasal
oral
rectal
subcutaneous
sublingual
transdermal
vaginal

DFS-0097

An absorptionModel shall be any of the following:

undefined
bolus
extra
extra.lag
infusion

DFS-0098

An absorptionParameters shall only contain parameterSetAnalyteGroup tags.

DFS-0099

A parameterSetAnalyteGroup shall contain one analyteGroupId, one absorptionModel, and one parameterSet.

DFS-0100

In a parameterSetAnalyteGroup, the analyteGroupId shall contain an Id that corresponds to an existing groupId in an ananyteGroup.

DFS-0101

In a parameterSetAnalyteGroup, the absorptionModel shall be a valid absorption model Id.

DFS-0159

In a formulationAndRoute, each parameterSetAnalyteGroup shall be using a different analyteGroupId. It means there should not be two groups of parameters for the same analyte group.

Dosages¶

dosages content¶
Tag name	Format	Occ.	Description
<dosages>			Available dosages associated with a formulation and route
____<standardTreatment>		0:1	A potential standard treatment
________<isFixedDuration>	bool	1:1	Has the treatment a fixed duration?
________<timeValue>		0:1	The duration of the fixed duration
____________<unit>		1:1	The unit of the duration
____________<value>		1:1	The duration value
____<analyteConversions>		1:1	List of analyte conversions
________<analyteConversion>		1:∞	Conversion from the quantity of drug to the quantity of analyte
____________<analyteId>	string	1:1	The Id of the analyte
____________<factor>	double	1:1	The factor to be multiplied to the drug quantity to obtain the analyte quantity
____<isLoadingDoseRecommended>	boolean	0:1	Is a loading dose recommended if the current dosage is too low?
____<isRestPeriodRecommended>	boolean	0:1	Is a rest period recommended if the current dosage is too high?
____<availableDoses>	AvailableDoses	1:1	Available doses
____<availableIntervals>	AvailableIntervals	1:1	Available intervals
____<availableInfusions>	AvailableInfusions	0:1	Available infusion times
____<comments>	Comments	1:1	Comments about the dosages

DFS-0102

A dosages shall have 0 or 1 standardTreatment, 0 or 1 isLoadingDoseRecommended, 0 or 1 isRestPeriodRecommended, one analyteConversions, one availableDoses, one availableIntervals, 0 or 1 availableInfusions and one comments.

If absorptionModel is infusion, there shall be one availableInfusions, else it shall not be present.

DFS-0103

A standardTreatment shall have one isFixedDuration.

DFS-0104

In a standardTreatment, if isFixedDuration is true, then there shall be a timeValue.

DFS-0105

A timeValue shall contain one unit and one value.

DFS-0106

In a timeValue, the unit shall be a valid Time unit.

DFS-0107

In a timeValue, the value shall be a valid positive floating point number.

DFS-0108

An analyteConversions shall contain at least one analyteConversion, and only analyteConversion tags.

DFS-0109

An analyteConversion shall contain one analyteId and one factor.

DFS-0110

In an analyteConversion, the analyteId shall be an identifier existing in an activeMoiety analyteId.

DFS-0111

A factor shall be a valid floating point number in the interval [0, 1].

DFS-0112

An availableDoses is an availableValues.

DFS-0113

In an availableDoses, the unit shall be a Weight unit.

DFS-0114

An availableIntervals is an availableValues.

DFS-0115

In an availableIntervals, the unit shall be a Time unit.

DFS-0116

An availableInfusions is an availableValues.

DFS-0117

In an availableInfusions, the unit shall be a Time unit.

AvailableValues¶

The available values are used for the doses, intervals and infusions. In the following example availableValues would be replaced by availableDoses, availableInfusions or availableIntervals.

availableValues content¶
Tag name	Format	Occ.	Description
<availableValues>			Available values
____<unit>		1:1	Unit of the values
____<default>	stdAprioriValue	1:1	Default value
____<rangeValues>		0:∞	Available values represented as a range
________<from>	stdAprioriValue	1:1	Starting value of the range
________<to>	stdAprioriValue	1:1	Ending value of the range
________<step>	stdAprioriValue	1:1	Step to be applied between from and to
____<fixedValues>		0:1	A list of fixed values
________<value>	double	1:1	A value

DFS-0118

An availableValues shall contain one unit, one default, any number of rangeValues, and 0 or 1 fixedValues.

DFS-0119

In an availableValues, default is an StdAprioriValue.

DFS-0120

A rangeValues shall contain one from, one to, and one step.

DFS-0121

In a rangeValues, from, to, and step are StdAprioriValue.

DFS-0122

In a rangeValues, from shall have a default value smaller than to.

DFS-0123

In a rangeValues, step shall have a strictly positive floating point number as default value.

DFS-0156

In a rangeValues, for the default values, step shall be strictly smaller than to - from.

DFS-0124

A fixedValues shall only contain value tags.

DFS-0125

In a fixedValues, a value shall contain a valid floating point number.

Time considerations¶

timeConsiderations content¶
Tag name	Format	Occ.	Description
<timeConsideration>			Some time considerations
____<halfLife>	halfLife	1:1	Half life of the drug
_______<unit>		1:1	Time unit of the half life
_______<duration>	stdAprioriValue	1:1	value of the half life
_______<multiplier>		1:1	Number of half lifes to reach steady state
_______<comments>	Comments	1:1	Comments about the half life
____<outdatedMeasure>	outdatedMeasure	1:1	Indication about the relevance of a measure
_______<unit>	string	1:1	Time unit
_______<duration>	stdAprioriValue	1:1	Time after which a measure shall be considered as irrelevant
_______<comments>	Comments	1:1	Comments about the outdate measure fields

DFS-0126

A timeConsiderations shall contain one halfLife and one outdatedMeasure.

DFS-0127

A halfLife shall contain one unit, one duration, one multiplier and one comments.

DFS-0128

In a halfLife, the unit shall be a valid Time unit.

DFS-0129

A duration is a StdAprioriValue.

DFS-0130

A duration default value shall be positive.

DFS-0131

A multiplier shall be a positive floating point number.

DFS-0132

An outdatedMeasure shall contain one unit, one duration and one comments.

DFS-0133

In an outdatedMeasure, the unit shall be a Time unit.

Parameters¶

parameterSet content¶
Tag name	Format	Occ.	Description
<parameterSet>		1:1	The absorption parameters
____<parameters>	Parameter	1:1	List of parameters
________<parameter>	Parameter	0:∞	A parameter
____<correlations>	Correlations	1:1	Correlations between absorption parameters or between absorption and disposition parameters
________<correlation>	Correlations	0:∞	Correlations between absorption parameters or between absorption and disposition parameters

DFS-0134

A parameterSet shall contain one parameters and one correlations.

DFS-0135

A parameters shall contain only parameter tags.

DFS-0136

A correlations shall contain only correlation tags.

Parameter structure:

parameter content¶
Tag name	Format	Occ.	Description
<parameter>			A Pk parameter
____<parameterId>	string	1:1	Id of the parameter
____<unit>	string	1:1	the unit of the parameter value
____<parameterValue>	stdAprioriValue	1:1	The parameter value and its optional apriori computation
____<bsv>	string	1:1	Between Subject Variability (BSV)
________<bsvType>	BsvType	1:1	Type of BSV
________<stdDevs>		0:1	A list of standard deviations
____________<stdDev>	double	1:∞	A standard deviation
____<validation>		1:1	A potential validation of the parameter value
________<errorMessage>		1:1	A translated list of error messages
____________<text>	string	1:∞	An error message, translated in a specific language
________<formula>	Operation	1:1	A formula to check the validity of the parameter
________<comments>	Comments	1:1	Comments about the validation
____<comments>	Comments	1:1	Comments about the parameter

DFS-0137

A parameter shall contain one parameterId, one unit, one parameterValue, one bsv, one validation, and one comments.

DFS-0138

A parameterId shall be a non-empty string.

DFS-0157

A parameterId shall be a parameter Id present in the selected Pk model.

The list of Pk models is as follows, with the potential parameter Ids. It is to be noted that not all parameters are mandatory, as the elimination parameters depend on the formulation and route.

pkModelParameters¶
pkModelId	Parameters
linear.1comp.macro	CL, V, Ka, F, Tlag
linear.2comp.macro	CL, V1, V2, Ka, F, Q, Tlag
linear.2comp.erlang1.macro	CL, V1, V2, Q, Ktr, F
linear.2comp.erlang1.micro	K12, K21, V1, Ke, Ktr, F
linear.2comp.erlang2.macro	CL, V1, V2, Q, Ktr, F
linear.2comp.erlang2.micro	K12, K21, V1, Ke, Ktr, F
linear.2comp.erlang3.macro	CL, V1, V2, Q, Ktr, F
linear.2comp.erlang3.micro	K12, K21, V1, Ke, Ktr, F
linear.2comp.erlang4.macro	CL, V1, V2, Q, Ktr, F
linear.2comp.erlang4.micro	K12, K21, V1, Ke, Ktr, F
linear.2comp.erlang5.macro	CL, V1, V2, Q, Ktr, F
linear.2comp.erlang5.micro	K12, K21, V1, Ke, Ktr, F
linear.2comp.erlang6.macro	CL, V1, V2, Q, Ktr, F
linear.2comp.erlang6.micro	K12, K21, V1, Ke, Ktr, F
michaelismenten.1comp	F, Ka, V, Km, Vmax
michaelismenten.2comp.macro	V1, Km, Vmax, V2, Q, F, Ka, Tlag
michaelismenten.2comp.micro	V1, Km, Vmax, K12, K21, F, Ka, Tlag
michaelismenten.2comp.vmaxamount.macro	V1, Km, Vmax, V2, Q, F, Ka, Tlag
michaelismenten.2comp.vmaxamount.micro	V1, Km, Vmax, K12, K21, F, Ka, Tlag
michaelismenten.enzyme.1comp	V, Km, Vmax, F, Ka, Kenz, Emax, ECmid, EDmid, DoseMid, Fmax, NN, MTT, AllmCL

DFS-0139

A parameterValue is a StdAprioriValue.

DFS-0140

A bsv shall contain one bsvType and one stdDevs.

DFS-0141

A bsvType is any of the following:

none
normal
lognormal
proportional
exponential
additive
logit

DFS-0142

An stdDevs shall contain zero stdDev if the bsvType is none, one stdDev else, and shall only contain stdDev tags.

DFS-0143

An stdDev shall be a valid positive floating point number.

Correlation structure:

Tag name	Format	Occ.	Description
<correlation>		0:∞	Description of the correlation
____<param1>	string	1:1	The first parameter’s ID
____<param2>	string	1:1	The second parameter’s ID
____<value>	double	1:1	The correlation’s value
____<comments>		1:1	Comments about the correlation

DFS-0145

A correlation shall contain one param1, one param2, one value, and one comments.

DFS-0146

A param1 shall reference an existing parameter Id of the model used.

DFS-0147

A param2 shall reference an existing parameter Id of the model used.

DFS-0148

In a correlation, param1 and param2 shall not be equal.

DFS-0149

In a correlation, value shall be a valid floating point number in the interval [-1,1].

StdAprioriValue¶

The StdAprioriValue is used at various places in the drug file.

DFS-0150

An stdAprioriValue shall contain one standardValue, and 0 or 1 aprioriComputation.

DFS-0151

A standardValue shall be a floating point number.

DFS-0152

An aprioriComputation is an Operation.

Unit¶

Weight unit¶

A valid weight unit is any of the following:

kg
g
mg
ug
µg
ng

Concentration unit¶

A valid concentration unit is any of the following:

g/l
mg/l
ug/l
µg/l
ng/l
g/dl
mg/dl
µg/dl
ug/dl
ng/dl
g/cl
mg/cl
µg/cl
ug/cl
ng/cl
g/ml
mg/ml
µg/ml
ug/ml
ng/ml

Temperature unit¶

A valid temperature unit is any of the following:

celsius

Flow rate unit¶

A valid flow rate unit is any of the following:

ml/min
l/min
ml/h
l/h

Mole Concentration unit¶

A valid mole concentration unit is any of the following:

kg/mol
g/mol
mg/mol
ug/mol
µg/mol
ug/umol
µg/umol
g/umol
kg/umol

Time unit¶

A valid time unit is any of the following:

y
month
d
h
min
s

Length unit¶

A valid length unit is any of the following:

m
cm
dm
mm
ft
in

Molar mass¶

A valid molar mass unit is any of the following:

g/mol
ug/mol
kg/mol
kg/umol

Concentration Time unit¶

A valid concentration times time unit is any of the following:

h*g/l
h*mg/l
h*ug/l
h*g/ml
h*mg/ml
h*ug/ml
g*h/l
mg*h/l
ug*h/l
g*h/ml
mg*h/ml
ug*h/ml
min*g/l
min*mg/l
min*ug/l
min*g/ml
min*mg/ml
min*ug/ml
g*min/l
mg*min/l
ug*min/l
g*min/ml
mg*min/ml
ug*min/ml

Empty unit¶

A valid absence of unit is any of the following:

empty string
“-”

Removed rules¶

The following rules have been removed.

DFS-0153

In a targetValues, the default value of inefficacyAlarm shall be smaller than the default value of toxicityAlarm.

Removed because redundant with other rules concerning inefficacy and toxicity.