Biomarker Validation: Technological, Clinical and Commercial Aspects

267 Pages·2015·2.814 MB·English

by  Harald Seitz, Sarah Schumacher

Editedby
HaraldSeitzandSarahSchumacher
BiomarkerValidation
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EditedbyHaraldSeitzandSarahSchumacher
Biomarker Validation
Technological,ClinicalandCommercialAspects
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V
Contents
ListofContributors XI
Preface XV
1 Biomarkers–PastandFuture 1
SiegfriedNeumann
1.1 Introduction 1
1.2 DefinitionsofBiomarkers 2
1.3 BiomarkersinthePast 3
1.4 NovelMoleculesandStructuralClassesofBiomarkers
byNewTechnologies 7
1.5 BiomarkersinDrugResearch 9
1.6 CurrentDevelopmentandFutureTrendsforBiomarkers
inLaboratoryDiagnostics 12
1.6.1 BiomarkerTestValidation 12
1.6.2 CompanionDiagnosticsinClinicalPharmacology 14
1.6.3 BiomarkerMultivariateIndexAssays 16
1.6.4 RegulatoryPoliciesonBiomarkerTests 17
1.7 SummaryandOutlook 19
References 20
2 QuantitativeProteomicsTechniquesinBiomarkerDiscovery 23
ThiloBracht,DominikAndreMegger,WaelNaboulsi,CorinnaHenkel,
andBarbaraSitek
2.1 Introduction 23
2.1.1 GeneralConsiderations 24
2.2 2D-DifferenceGelElectrophoresis 27
2.3 MassSpectrometry-BasedProteomics 29
2.3.1 PrinciplesandInstrumentation 29
2.3.1.1 IonizationMethods 29
2.3.1.2 MassAnalyzers 30
2.3.2 Label-FreeProteinQuantification 30
2.3.2.1 AreaUnderCurve(AUC)orSignalIntensityMeasurement 30
2.3.2.2 SpectralCounting 31
VI Contents
2.3.3 Label-BasedProteomeAnalysis 31
2.4 MALDIMassSpectrometryImaging 33
2.5 Conclusion 36
References 36
3 BiomarkerQualification:ACompanyPointofView 39
MaximilianBreitner,KaïdreBendjama,andHüseyinFirat
3.1 Introduction 39
3.2 BiomarkerUses 40
3.3 BiomarkerTypes 41
3.4 Validationvs.Qualification 43
3.5 StrategicChoicesinBusinessModels 43
3.6 ValidationofAnalyticalMethods 44
3.6.1 CurrentlyApplicableGuidelinesfortheValidationofAnalytical
Methods 45
3.6.2 LaboratoryProficiency 46
3.6.3 EstablishmentofReferenceRangesforCandidateBiomarkers 46
3.7 ClinicalQualificationofCandidateBiomarkers 47
3.7.1 MethodologicalApproaches 47
3.7.2 StudySizeforBiomarkerPerformanceCharacterization 48
3.7.3 SampleQualityandBiobanking 50
3.7.3.1 SampleCollection 50
3.7.3.2 StorageofSample 51
3.7.3.3 ClinicalData(SampleAnnotation) 52
3.7.3.4 EthicalConsiderations 53
3.8 BiomarkerQualificationinthe‘omicsEra 53
3.9 AnExampleofaBiomarkerProvider 54
3.10 Conclusion 55
References 55
4 BiomarkerDiscoveryandMedicalDiagnosticImaging 59
AndreasP.SakkaandJamesR.Whiteside
4.1 Introduction 59
4.1.1 ImagingModalities 59
4.1.1.1 PositronEmissionTomography(PET) 59
4.1.1.2 SinglePhotonEmissionComputedTomography(SPECT) 60
4.1.1.3 ComputedTomography(CT) 60
4.1.1.4 MagneticResonanceImaging(MRI) 60
4.1.1.5 Ultrasound(US) 61
4.2 FactorstoConsiderinBiomarkerSelectionforImaging 61
4.3 DefiningtheInsertionPointoftheAssayandItsBusinessCase 62
4.4 PracticalInVitroMethodsUsedtoIdentifyBiomarkers 63
4.5 PreclinicalModels 64
4.5.1 ModelSpecies 64
Contents VII
4.5.2 InducingHumanDiseaseandRelevantBiomarker
Expression 64
4.5.3 GeneticManipulation 65
4.5.4 Pharmacological/ChemicalInduction 65
4.5.5 Xenografts:GraftingForeignCellsorTissues 66
4.5.6 PhysicalInduction 66
4.6 PreclinicalAnalysisTechniques 67
4.7 TranslationalConsiderationsandRestrictions 67
4.8 OtherUsesofPreclinicalModels 68
4.9 NuclearImagingInfrastructure 69
4.10 ImageProcessing 70
4.11 ConcludingRemarks 70
References 71
5 Breath:AnOftenOverlookedMediuminBiomarkerDiscovery 75
JonathanDBeauchampandJoachimDPleil
5.1 Introduction 75
5.1.1 BreathAnalysis:PastandPresent 76
5.2 BreathAnalysisStudies:Targets,Techniques,andApproaches 77
5.2.1 ExhaledBreathGas,Condensate,andAerosols 79
5.2.2 SamplingTechniquesandAnalyticalTools 80
5.2.3 DiscoveryVersusTargetedStudyApproaches 81
5.3 BiomarkerConfounders 83
5.3.1 SamplingImpact 83
5.3.1.1 OnlineBreathSamplingandDirectAnalysis 84
5.3.1.2 BreathSamplingforOfflineAnalysis 84
5.3.2 ContributionsfromtheExposome 85
5.4 BiomarkersinBreath 86
5.4.1 InorganicBreathBiomarkers 86
5.4.2 OrganicBiomarkersinBreath 87
5.5 OutlookforBreathAnalysis 88
Acknowledgments 90
References 90
6 HTAinPersonalizedMedicineTechnologies 95
FranzHessel
6.1 Introduction 95
6.2 HealthTechnologyAssessment(HTA) 96
6.3 ValidationandEvaluationofBiomarkerTests 99
6.4 HealthTechnologyAssessmentofPersonalizedMedicine
Technologies 100
6.5 ConcludingRemarks 104
References 105
VIII Contents
7 BoneRemodelingBiomarkers:NewActorsontheOldCardiovascular
Stage 107
CristinaVassalle,SilviaMaffei,andGiorgioIervasi
7.1 Introduction 107
7.2 CardiovascularDiseaseandOsteoporosis:CommonRiskFactors
andCommonPathophysiologicalMechanisms 108
7.3 BiomarkersofBoneHealthinCVD 112
7.3.1 CathepsinK 112
7.3.2 Tartrate-ResistantAcidPhosphatase 115
7.3.3 Sclerostin 115
7.3.4 FibroblastGrowthFactor23 116
7.3.5 Osteopontin 116
7.3.6 Osteocalcin 117
7.3.7 Osteoprotegerin 118
7.3.8 VitaminD 120
7.3.9 OtherFactors 121
7.3.10 GeneticFactors 123
7.4 Conclusion 125
References 128
8 IdentificationandValidationofBreastCancerBiomarkers 147
KoriJacksonandEdwardSauter
8.1 Introduction 147
8.2 CurrentDetectionandTreatmentModalities 148
8.2.1 Detection:InClinicalUse 148
8.2.1.1 PhysicalExamination 148
8.2.1.2 BreastImaging 148
8.2.2 Detection:BeingEvaluated 149
8.2.2.1 BodilyFluidAnalyses 150
8.2.3 Treatment:InClinicalUse 150
8.2.3.1 SurgeryandRadiation 150
8.2.3.2 SystemicTherapy 151
8.2.4 Treatment:BeingEvaluated/NewlyAvailable 153
8.2.4.1 BiomarkersinTissue:SingleMarkers 153
8.2.4.2 BiomarkersinTissue:GenePanels 154
8.3 CurrentBiomarkerLimitations 154
8.3.1 TumorHeterogeneity 154
8.3.2 TreatmentEffect 155
8.3.3 PrimaryVersusRecurrentTumor 155
8.4 FutureBiomarkerDiscoveryTargets 156
8.4.1 Autoantibodies 156
8.4.2 InflammatoryMarkers 156
8.4.3 DNAMethylation 157
8.4.4 BenignBreastDisease 157
8.4.5 Pregnancy-AssociatedBreastCancer 157