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Fixes #1755 aucr cmax r not calculated properly #2093

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merged 1 commit into from
Feb 15, 2022
Merged

Fixes #1755 aucr cmax r not calculated properly #2093

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4 changes: 2 additions & 2 deletions src/PKSim.Core/Model/Simulation.cs
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Original file line number Diff line number Diff line change
Expand Up @@ -444,11 +444,11 @@ public virtual void UpdateFromOriginalSimulation(Simulation originalSimulation)
}

/// <summary>
/// Returns the endtime of the simulation in kernel unit
/// Returns the end time of the simulation in kernel unit
/// </summary>
public virtual double? EndTime
{
get { return OutputSchema.Intervals.Select(x => x.EndTime.Value).Max(); }
get { return OutputSchema?.Intervals.Select(x => x.EndTime.Value).Max(); }
}

/// <summary>
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21 changes: 14 additions & 7 deletions src/PKSim.Core/Services/GlobalPKAnalysisTask.cs
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Original file line number Diff line number Diff line change
@@ -1,14 +1,14 @@
using System.Collections.Generic;
using System.Linq;
using PKSim.Assets;
using OSPSuite.Core.Domain;
using OSPSuite.Core.Domain.Data;
using OSPSuite.Core.Domain.Services;
using OSPSuite.Utility.Extensions;
using OSPSuite.Utility.Validation;
using PKSim.Assets;
using PKSim.Core.Mappers;
using PKSim.Core.Model;
using PKSim.Core.Model.Extensions;
using OSPSuite.Core.Domain;
using OSPSuite.Core.Domain.Data;
using OSPSuite.Core.Domain.Services;
using IParameterFactory = PKSim.Core.Model.IParameterFactory;

namespace PKSim.Core.Services
Expand Down Expand Up @@ -123,10 +123,10 @@ public GlobalPKAnalysis CalculateGlobalPKAnalysisFor(IEnumerable<Simulation> sim
continue;
}

var schemaItem = singleDosingItem(simulation, compound);
var pkValues = new List<IParameter>();
var bioAvailabilityCalculated = !double.IsNaN(bioAvailabilityValue);

var schemaItem = singleDosingItem(simulation, compound);
if (isIntravenous(schemaItem))
{
container.AddChildren(vssPlasma, vdPlasma, vssPhysChem, totalPlasmaCL);
Expand Down Expand Up @@ -319,17 +319,23 @@ private bool isMultipleOral(Simulation simulation, Compound compound)

private static bool isOral(ISchemaItem schemaItem)
{
if (schemaItem == null)
return false;

return schemaItem.ApplicationType == ApplicationTypes.Oral;
}

private static bool isIntravenous(ISchemaItem schemaItem)
{
if (schemaItem == null)
return false;

return schemaItem.ApplicationType == ApplicationTypes.Intravenous || schemaItem.ApplicationType == ApplicationTypes.IntravenousBolus;
}

private ApplicationType applicationTypeFor(Simulation simulation, Compound compound)
{
var numberOfApplications = schemaItemsFrom(simulation, compound).Count;
var numberOfApplications = simulation.AllApplicationParametersOrderedByStartTimeFor(compound.Name).Count;
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This is the only relevant difference, correct?
For a metabolite (which is not administered) number of applications was zero before; now it is number of applications of its parent drug, right?

By the way, I would rename the function AllApplicationParametersOrderedByStartTimeFor to something like AllOrderedApplicationStartTimes.
Because in AllApplicationParameters I would expect also all other application parameters like e.g. DrugMass, InfusionTime etc. (I had to look into the implementation of the function to understand what it does)

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ok but this is in core so not directly relevant to this problem. Please create an issue for this

For a metabolite (which is not administered) number of applications was zero before; now it is number of applications of its parent drug, right?

yes

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Issue created: Open-Systems-Pharmacology/OSPSuite.Core#1494
PR looks good for me

if (numberOfApplications == 1)
return ApplicationType.Single;

Expand All @@ -338,7 +344,8 @@ private ApplicationType applicationTypeFor(Simulation simulation, Compound compo

private ISchemaItem singleDosingItem(Simulation simulation, Compound compound)
{
return schemaItemsFrom(simulation, compound)[0];
//this may be null for compound created by metabolization process only
return schemaItemsFrom(simulation, compound).FirstOrDefault();
}

private IReadOnlyList<ISchemaItem> schemaItemsFrom(Simulation simulation, Compound compound)
Expand Down
40 changes: 26 additions & 14 deletions tests/PKSim.Tests/Core/GlobalPKAnalysisTaskSpecs.cs
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Original file line number Diff line number Diff line change
@@ -1,16 +1,16 @@
using System;
using System.Collections.Generic;
using FakeItEasy;
using OSPSuite.BDDHelper;
using OSPSuite.BDDHelper.Extensions;
using FakeItEasy;
using PKSim.Core.Mappers;
using PKSim.Core.Model;
using PKSim.Core.Services;
using OSPSuite.Core.Domain;
using OSPSuite.Core.Domain.Builder;
using OSPSuite.Core.Domain.Data;
using OSPSuite.Core.Domain.Formulas;
using OSPSuite.Core.Domain.Services;
using OSPSuite.Core.Domain.UnitSystem;
using PKSim.Core.Mappers;
using PKSim.Core.Model;
using PKSim.Core.Services;
using IParameterFactory = PKSim.Core.Model.IParameterFactory;
using IPKAnalysesTask = PKSim.Core.Services.IPKAnalysesTask;
using IPKCalculationOptionsFactory = PKSim.Core.Services.IPKCalculationOptionsFactory;
Expand All @@ -36,10 +36,12 @@ public abstract class concern_for_GlobalPKAnalysisTask : ContextSpecification<IG
protected PKValues _peripheralVenousBloodPK;
protected Species _species;
protected SimpleProtocol _protocol;
protected List<SchemaItem> _simulationSchemaItems;
private IInteractionTask _interactionTask;
protected Compound _compound;
private ICloner _cloner;
protected EventGroup _eventGroup;
private Container _application1;
protected Container _application2;

protected override void Context()
{
Expand All @@ -65,18 +67,28 @@ protected override void Context()

_compound = new Compound().WithName(_compoundName);
_compoundProperties = new CompoundProperties {Compound = _compound};
_simulationSchemaItems = new List<SchemaItem>();
_protocol = new SimpleProtocol();
_compoundProperties.ProtocolProperties.Protocol = _protocol;
A.CallTo(() => _protocolMapper.MapFrom(_protocol)).Returns(_simulationSchemaItems);

_simulation = new IndividualSimulation {Properties = new SimulationProperties()};

_simulation.Properties.AddCompoundProperties(_compoundProperties);
_simulation.AddUsedBuildingBlock(new UsedBuildingBlock("CompId", PKSimBuildingBlockType.Compound) {BuildingBlock = _compound});
_simulation.AddUsedBuildingBlock(new UsedBuildingBlock("IndividualId", PKSimBuildingBlockType.Individual) {BuildingBlock = _individual});
_simulation.DataRepository = new DataRepository {_venousBloodPlasma, _peripheralVenousBloodPlasma};

_simulation.SimulationSettings = new SimulationSettings();
_simulation.OutputSchema = new OutputSchema();
_simulation.OutputSchema.AddInterval(new OutputInterval{DomainHelperForSpecs.ConstantParameterWithValue(100).WithName(Constants.Parameters.END_TIME) });
_simulation.Model = new OSPSuite.Core.Domain.Model {Root = new Container()};
_eventGroup = new EventGroup();
_application1 = new Container().WithName("App1").WithContainerType(ContainerType.Application);
_application1.Add(new MoleculeAmount().WithName(_compoundName));
_application1.Add(DomainHelperForSpecs.ConstantParameterWithValue(10).WithName(Constants.Parameters.START_TIME));
_application2 = new Container().WithName("App2").WithContainerType(ContainerType.Application);
_application2.Add(DomainHelperForSpecs.ConstantParameterWithValue(10).WithName(Constants.Parameters.START_TIME));
_application2.Add(new MoleculeAmount().WithName(_compoundName));
_simulation.Model.Root.Add(_eventGroup);
_eventGroup.Add(_application1);
_venousBloodPK = new PKValues();
_venousBloodPK.AddValue(Constants.PKParameters.Vss, 10);
_venousBloodPK.AddValue(Constants.PKParameters.Vd, 11);
Expand Down Expand Up @@ -113,7 +125,7 @@ protected DataColumn CalculationColumnFor(BaseGrid baseGrid, string organ, strin
}
}

public class When_calculating_the_global_pk_analyes_parameter_such_as_VSS_VD_and_Plasma_CL_for_the_human_species : concern_for_GlobalPKAnalysisTask
public class When_calculating_the_global_pk_analyses_parameter_such_as_VSS_VD_and_Plasma_CL_for_the_human_species : concern_for_GlobalPKAnalysisTask
{
private GlobalPKAnalysis _results;

Expand Down Expand Up @@ -309,7 +321,9 @@ protected override void Context()
var startTime = DomainHelperForSpecs.ConstantParameterWithValue(3);
A.CallTo(() => schemaItem.Dose).Returns(inputDose);
A.CallTo(() => schemaItem.StartTime).Returns(startTime);
_simulationSchemaItems.Add(schemaItem);

A.CallTo(() => _protocolMapper.MapFrom(_protocol)).Returns(new []{schemaItem, });

}

protected override void Because()
Expand Down Expand Up @@ -361,8 +375,6 @@ protected override void Context()

A.CallTo(() => _globalPKAnalysisRunner.RunForDDIRatio(_simulation)).Returns(_ddiRatioSimulation);
A.CallTo(() => _pkAnalysisTask.CalculateFor(_ddiRatioSimulation, _peripheralVenousBloodPlasma)).Returns(new IndividualPKAnalysis(_peripheralVenousBloodPlasma, _pkAnalysis));
//single dosing
_simulationSchemaItems.Add(new SchemaItem());
}

protected override void Because()
Expand Down Expand Up @@ -444,7 +456,7 @@ protected override void Context()
A.CallTo(() => _globalPKAnalysisRunner.RunForDDIRatio(_simulation)).Returns(_ddiRatioSimulation);
A.CallTo(() => _pkAnalysisTask.CalculateFor(_ddiRatioSimulation, _peripheralVenousBloodPlasma)).Returns(new IndividualPKAnalysis(_peripheralVenousBloodPlasma, _pkAnalysis));
//multiple dosing
_simulationSchemaItems.AddRange(new[] {new SchemaItem(), new SchemaItem()});
_eventGroup.Add(_application2);
}

protected override void Because()
Expand Down