Stephens' Detection of New Adverse Drug Reactions

763 Pages·2004·3.46 MB·English

by  John Talbot

Stephens’ Detection of
New Adverse Drug Reactions
Fifth Edition
Edited by
John Talbot
Director,GlobalDrugSafety,AstraZenecaR&DCharnwood,Loughborough,
Leicestershire,UK
Patrick Waller
ConsultantinPharmacovigilanceandPharmacoepidemiology,Southampton,UK

Stephens’ Detection of
New Adverse Drug Reactions
Fifth Edition

Stephens’ Detection of
New Adverse Drug Reactions
Fifth Edition
Edited by
John Talbot
Director,GlobalDrugSafety,AstraZenecaR&DCharnwood,Loughborough,
Leicestershire,UK
Patrick Waller
ConsultantinPharmacovigilanceandPharmacoepidemiology,Southampton,UK
Copyright#2004 JohnWiley&SonsLtd,TheAtrium,SourthernGate,Chichester,
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Contents
Foreword xi
Preface xiii
ListofContributors xv
1 Introduction 1
M.D.B.Stephens
Mercury 1
Introductiontopharmacovigilance 1
Thehistoryofpharmacovigilance 3
Under-reportingofadversedrugreactions 10
Incidenceofadversedrugreactions 17
Thefinancialcostofadversedrugreactions 30
Preventabilityofadversedrugreactions 35
Risk–benefitratio 35
Thechangingriskswithnewdrugs 44
Expressionofrisk 47
Theriskswearepreparedtotake 52
Definitions 57
Classificationofadversedrugreactions 58
Adversereactionprofile 60
Adverseeventsinapatient’slife 61
Symptomsinhealthypersons 62
Adversereactionstoplacebo 63
Infectiousnessofadversedrugreactions 67
Herbalmedicines 69
Somefinalfoodforthought 70
References 71
Furtherreading 88
2 AdverseDrugReactionsandInteractions:Mechanisms,RiskFactors,
Detection,ManagementandPrevention 92
P.Routledge
Introduction 92
Classificationofadversedrugreactions 92
RiskfactorsfortypeAadversereactions 93
RiskfactorsfortypeBadversereactions 101
Detectionofadversedrugreactions 106
Stephens’DetectionofNewAdverseDrugReactionsFifthEditioneditedbyJohnTalbotandPatrickWaller
#2004JohnWiley&Sons,Ltd ISBN:047084552X
vi CONTENTS
Managementofadversedrugreactions 108
Preventionofadversedrugreactions 109
Druginteractions 111
Conclusions 122
References 122
3 ToxicologyandAdverseDrugReactions 128
D.J.Snodin
Introduction 128
Toxicitytesting 128
Drugdevelopment 137
Datainterpretationandriskassessment 144
Adversedrugreactionsdetectedafterauthorization 150
Examplesoftoxicologicalinvestigationofadversedrugreactions 157
Conclusions 159
Acknowledgements 159
References 159
4 ClinicalTrials:CollectionofSafetyDataandEstablishingthe
AdverseDrugReactionProfile 167
J.C.C.Talbot,M.D.B.Stephens
Introduction 167
Adverseevents 168
Finalanalysisofdata 229
Inadequatereportingofsafetydatafromclinicaltrials 231
Conclusions 232
Futureaspirations 233
Acknowledgements 233
References 233
5 ClinicalLaboratorySafetyDatainDrugStudies 244
A.Craig
Introduction 244
Factorsthatinfluenceinterpretationofclinicallaboratorydata 245
Samplecollectionprocedure 252
Analyticalvariation 255
Referenceranges 256
Intra-individualbiologicalvariation 259
Safetytestingindrugdevelopment 261
Testselection 289
Exclusioncriteriaand‘paniclevels’ 290
Harmonizationofdatafromdifferentlaboratories 292
Dataanalysisandpresentation 294
Conclusion 298
References 298
CONTENTS vii
6 Statistics:AnalysisandPresentationofSafetyData 301
S.J.W.Evans
Introductionandbackground 301
Analysisandpresentationofdatafromtrials 305
Measuresthattaketimeintoaccount 308
Statisticaltestsutilizingtimesincestartoftreatment 310
Combiningdatafromseveraltrials:meta-analysis 312
Analysisandpresentationofdatafromobservationalstudies 312
Useofstatisticalmethodsforsignaldetectionwithspontaneousreports 316
Summaryandconclusions 325
Acknowledgements 326
References 326
7 CausalityandCorrelationinPharmacovigilance 329
S.A.W.Shakir
Introductionandhistoricalbackground 329
Thenotionsofnecessaryandsufficientcauses 330
Factorstobeconsideredincausalityassessment 330
Methodsforcausalityassessment 333
Whentoassesscausality 336
Assessingcausalityfrommultipleinformationsources:theBradford-Hillcriteria 337
Conclusion 342
References 342
8 ManagingDrugSafetyIssueswithMarketedProducts 345
P.C.Waller,H.H.Tilson
Introduction 345
Identificationofdrugsafetyissues 346
Investigation 356
Evaluation 359
Action 361
Communicatingaboutdrugsafety 364
Beyondcommunication:riskmanagement 369
Managingtheprocess 371
Conclusion:somethoughtsonthefuture 372
References 373
9 RegulatoryAspectsofPharmacovigilance 375
B.D.C.Arnold
Introduction 375
CouncilforInternationalOrganizationsofMedicalSciences 375
TheInternationalConferenceonHarmonization 379
TheEuropeanUnion 399
TheUnitedKingdom 419
France 424
Germany 428
UnitedStatesofAmerica 432
viii CONTENTS
Japan 443
Acknowledgements 448
References 449
Bibliography 449
10 LegalAspectsofPharmacovigilance 453
C.Bendall
Introduction 453
Legalresponsibilityforpharmacovigilance 454
Interpretinglegalprovisions 458
TherelationshipbetweenEuropeanCommunitypharmacovigilancelegislationand
guidelines 460
Nationalimplementation 461
UncertaintiesinEuropeanCommunityprovisions 463
Thepotentialimpactofthe2001reviewofpharmaceuticallegislation 468
Europeanpowersandproceduresintheeventofaproductsafetyissue 469
ReferraltotheCommitteeforProprietaryMedicinalProducts 471
Failurestomeetadversedrugreactionreportingrequirements 478
Consequencesoffailuretomeetrequirements 481
Safetyinresearchproducts 487
Personaldataprivacy 490
Reference 491
11 OperationalAspectsoftheDrugSafetyFunctionwithina
PharmaceuticalCompany 493
J.Steiner
Introduction 493
Overviewofthecase-handlingprocess 493
Specificsofthecase-handlingprocess 494
Periodicsafetyupdates 499
Staffingmodelsforthecase-handlingprocess 504
Technologyandthecase-handlingprocess 508
Qualitycontrolandthecase-handlingprocess 513
Trainingandthecase-handlingprocess 520
Externalpartnersandthecase-handlingprocess 525
Casedistributiontoexternalpartiesotherthanregulatoryauthorities 527
Conclusion:visionforthefuture 531
Acknowledgement 531
References 531
Furtherreading 532
12 DictionariesandCodinginPharmacovigilance 533
E.Brown
Introduction 533
Scopeofthischapter 534
Drugdictionaries 534
Adversedrugreactiondictionaries 537