Principles and Practice of Pharmaceutical Medicine, Third Edition

787 Pages·2010·18.66 MB·English

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Principles and
Practice of
Pharmaceutical
Medicine
EDITED BY
Lionel D. Edwards
PresidentPharmaProPlusInc.NewJersey,andAdjunctProfessor,
TempleUniversity,SchoolofPharmacy,Philadelphia,USA
Anthony W. Fox
EBDGroupInc.,California,USAandMunich,Germany,andAdjunctAssociateProfessor,
SkaggsSPPS,UniversityofCalifornia,SanDiego,USA
Peter D. Stonier
SchoolofBiomedical&HealthSciences,King’sCollegeLondon,UK
THIRD EDITION
A John Wiley & Sons, Ltd., Publication
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Thiseditionfirstpublished2011,(cid:1)C 2011byBlackwellPublishingLtd.
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LibraryofCongressCataloging-in-PublicationData
Principlesandpracticeofpharmaceuticalmedicine/editedbyLionelD.
Edwards,AnthonyW.Fox,PeterD.Stonier.–3rded.
p.;cm.
Includesbibliographicalreferencesandindex.
ISBN978-1-4051-9472-3
1.Drugdevelopment. 2.Drugs–Research. 3.Pharmacology. I.Edwards,LionelD. II.Fox,AnthonyW.,
1956- III.Stonier,P.D.
[DNLM:1.DrugEvaluation. 2.DrugIndustry–organization&administration. QV736]
RM301.25.P75 2010
615(cid:2).19–dc22
2010027197
AcataloguerecordforthisbookisavailablefromtheBritishLibrary.
Setin9/12ptMeridienbyAptara(cid:1)R Inc.,NewDelhi,India
PrintedinSingapore
1 2011
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Contents
Contributors,vii
PrefacetotheFirstEdition,x
PrefacetotheSecondEdition,xi
PrefacetotheThirdEdition,xii
AbouttheEditors,xiii
Section I Overview of Pharmaceutical Medicine
1 ThePracticeandPractitionersofPharmaceuticalMedicine,3
AnthonyW.Fox
2 PharmaceuticalMedicineasaMedicalSpecialty,6
MichaelD.Young&PeterD.Stonier
3 ClinicalResearchEducationandTrainingforBiopharmaceuticalStaff,22
PeterMarks&SheilaGwizdak
Section II Drug Discovery and Development
4 DrugDiscovery:DesignandDevelopment,39
RonaldR.Cobb&LeslieJ.Molony
5 TranslationalMedicine,PharmaceuticalPhysicians,Patients,andPayers,47
RobertSands&DouglasRoy
6 Pharmaceutics,58
AnthonyW.Fox
7 NonclinicalToxicology,68
FrederickReno
8 InformedConsent,79
AnthonyW.Fox
9 PhaseI:TheFirstOpportunityforExtrapolationfromAnimalDatatoHuman
Exposure,84
StephenH.Curry,HelenH.DeCory,&JohanGabrielsson
10 PhaseIIandPhaseIIIClinicalStudies,107
AnthonyW.Fox
11 PhaseIVDrugDevelopment:Post-marketingStudies,124
LisaR.Johnson-Pratt
iii
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iv Contents
12 SiteManagement,131
BarryMiskin
13 GoodClinicalPractices,142
LionelD.Edwards
14 QualityAssurance,QualityControlandAudit,163
RitaHattemer-Apostel
15 TheUniqueRoleofOver-the-CounterMedicine,182
PaulStarkey
Section III Special Populations and Required Special Studies
16 DrugResearchinOlderPatients,197
LionelD.Edwards
17 DrugDevelopmentResearchinWomen,207
LionelD.Edwards
18 ClinicalResearchinChildren,226
LionelD.Edwards
19 RacialandEthnicIssuesinDrugRegulation,233
LionelD.Edwards,J-M.Husson,E.Labbe´,C.Naito,M.PapalucaAmati,S.Walker,
R.L.,Williams,&H.Yasurhara
20 SpecialPopulations:HepaticandRenalFailure,250
AnthonyW.Fox
21 DrugInteractions,255
AnthonyW.Fox&Anne-RuthvanTroostenburg
22 OrphanDrugs,264
BertSpilker
23 QTIntervalProlongationandDrugDevelopment,275
BruceH.Morimoto&AnthonyW.Fox
Section IV Applied Aspects
24 BiotechnologyProductsandTheirDevelopment,289
DavidA.Shapiro&AnthonyW.Fox
25 HealthEconomics,301
DanielC.Malone,EdwardP.Armstrong,&MirzaI.Rahman
26 Pharmacoeconomics:EconomicandHumanisticOutcomes,315
RaymondJ.Townsend,JaneT.Osterhaus,&J.GregoryBoyer
27 PharmacoepidemiologyandthePharmaceuticalPhysician,326
HughH.Tilson
28 StatisticalPrinciplesandApplicationinBiopharmaceuticalResearch,336
DanAnbar
29 DataManagement,368
T.Y.Lee,MichaelMinor,&LionelD.Edwards
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Contents v
30 PatientCompliance:Pharmionics,ANewDiscipline,379
Dr.Jean-MichelMe´try
31 MonitoringDrugConcentrationsinClinicalPractice,388
AnthonyW.Fox
32 Generics,393
GabrielLopez&ThomasHoxie
33 ComplementaryMedicines,399
AnthonyW.Fox
Section V Drug Regulation
34 UnitedStatesRegulations,409
WilliamKennedy&LionelDEdwards
35 SpecialUSRegulatoryProcedures:Emergencyand“Compassionate”INDsand
AcceleratedProductApprovals,422
AnthonyW.Fox
36 TheDevelopmentofHumanMedicinesControlinEuropefromClassicalTimesto
the21stCentury,430
JohnP.Griffin
37 MedicinesRegulationintheEuropeanUnion,456
A-R.vanTroostenburg&G.Tabusso
38 JapaneseRegulations,509
EtienneLabbe´
39 DrugRegistrationandPricingintheMiddleEast,528
EddaFreidank-Mueschenborn&AnjaKo¨nig
40 China’sRegulatedPharmaceuticalMarket,535
YanYanLiStarkey
41 India’sNewErainPharmaceuticals,551
DarshanKulkarni
Section VI Medical Services
42 MedicalAffairs,571
GregoryP.Geba
43 DrugLabeling,582
AnthonyW.Fox
44 DataMining,587
MirzaI.Rahman&RobbertP.vanManen
45 RiskManagementinProductApprovalandMarketing,601
AnthonyW.Fox
46 PublishingClinicalStudies,608
AnthonyW.Fox
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vi Contents
47 OrganizingandPlanningLocal,Regional,National,andInternationalMeetingsand
Conferences,616
ZofiaDziewanowska&LindaPackard
48 WhenThingsGoWrong:DrugWithdrawalsfromtheMarket,620
RonaldD.Mann
49 InternationalTrials:SuccessfulPlanningandConduct,625
KatieP.J.Wood
Section VII Legal and Ethical Aspects of Pharmaceutical Medicine
50 IntroductiontoBioethicsforPharmaceuticalProfessionals,637
AndrewJ.Fletcher
51 PharmaceuticalMedicineandtheLaw,645
SarahCroft
52 FraudandMisconductinClinicalResearch,655
JaneBarrett
Section VIII Business Aspects
53 TheMultinationalCorporations:CulturalChallenges,theLegal/Regulatory
FrameworkandtheMedico-commercialEnvironment,669
R.Drucker&R.GrahamHughes
54 AdvertisingandMarketing,676
JonathanBelsey
55 PharmaceuticalProductLiability,688
HanW.Choi&JaeHongLee
56 Patents,703
GabrielLopez
57 OutsourcingClinicalDrugDevelopmentActivitiestoContractResearch
Organizations(CROs):CriticalSuccessFactors,716
JohnR.Vogel
58 TheImpactofManagedCareontheUSPharmaceuticalIndustry,739
RobertJ.Chaponis,ChristineHanson-Divers,&MarilynJ.Wells
Appendix:UsefulWebLinks,762
Index,764
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Contributors
Anbar,Dan Dziewanowska,Zofia
DANAPharmaceuticalConsulting,Inc.,NJ,USA NewDrugAssociates,Inc.,LaJolla,CA,USA
Email:[email protected] Email:zofi[email protected]
Armstrong,Edward Fletcher,AndrewJ.
PharmacyPracticeandScience,CollegeofPharmacy, TempleUniversitySchoolofPharmacy,PHARM-QA/RA,
UniversityofArizona,USA Philadelphia,PA,USA
Email:andrew.fl[email protected]
Barrett,Jane
Gawsworth,Cheshire,UK Freidank-Mueschenborn,Edda
Email:[email protected] Bungalowsiedlung1B,D-17406Rankwitz,Germany
Belsey,Jonathan Gabrielsson,Johan
JBMedicalLtd,Sudbury,Suffolk,UK AstraZenecaAB,Gothenburg,Sweden
Email:[email protected]
Geba,GregoryP.
Boyer,J.Gregory ClinicalDevelopment,MedImmune,LLC,Gaithersburg,MD
AccreditationCouncilforPharmacyEducation, Email:[email protected]
Chicago,ILL,USA
Griffin,JohnP.
Chaponis,RobertJ. AsklepieionConsultancyLtd,Welwyn,Hertfordshire,UK
Novartis,Parsippany,NJ,USA Email:[email protected]
Email:[email protected]
SheilaGwizdak
Choi,HanW. PfizerInc.,NewLondon,CT,USA
OracleInvestmentManagement,Inc.,Greenwich,CT,USA
Email:[email protected] Hanson-Divers,Christine
AstraZeneca,Cary,NC,USA
Cobb,RonaldR.
Hattemer-Apostel,Rita
RiverWoodBioConsultingInc.,Gainesville,FL,USA
VerdandiAG,8049Zurich,Switzerland
Email:[email protected]
Email:[email protected]
Croft,Sarah
Hoxie,Thomas
Shook,HardyandBaconInternationalLLP,London,UK
Hoxie&AssociatesLLC,Millburn,NJ,USA
Email:[email protected]
Husson,Jean-Marc
Curry,Stephen,H.
Paris,France
UniversityofRochester,Rochester,NY,USA
Email:[email protected] Hughes,R.Graham
ConsultantinPharmaceuticalDevelopment,Merlimont,
DeCory,HelenH. France
BauschandLombInc.,Rochester,NY,USA
Johnson-Pratt,LisaR.
Drucker,R. BrynMawr,PA,USA
TechnomarkLifeSciencesLLP,Durham,NC,USA Email:[email protected]
vii
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viii Contributors
Kennedy,William Morimoto,BruceH.
AllonTherapeuticsInc.,RedwoodCity,CA,USA
Email:[email protected]
Ko¨nig,Anja
EngelhardArzneimittelAG,Niederdorfelden,Germany
Naito,C.
Kulkarni,Darshan TeikyoUniversity,Tokyo,Japan
TheKulkarniLawFirm,Philadelphia,PA,USA
Email:[email protected] Osterhaus,JaneT.
WasatchHealthOutcomes,ParkCity,UT,USA
Labbe´,Etienne Email:[email protected]
UCBS.A.,Brussels,Belgium
Packard,Linda
Lee,JaeHong AmericanAcademyofPharmaceuticalPhysicians,Research
Morrison&FoersterLLP,SanDiego,CA,USA TrianglePark,NC,USA
Email:[email protected]
PapalucaAmati,Marisa
Lee,T.Y. EuropeanAgencyfortheEvaluationofMedicinalProducts,
ClinicalDevelopmentandAsianVentures,Kendle London,UK
InternationalInc.,Cincinnati,OH,USA
Rahman,MirzaI.
Lopez,Gabriel HealthEconomicsandReimbursement,EvidenceBased
BaskingRidge,NJ,USA Medicine,Ortho-ClinicalDiagnostics,Inc.,Rochester,
Email:[email protected] NY,USA
Email:[email protected]
Malone,Daniel
PharmacyPracticeandScience,CollegeofPharmacy, Reno,Fred(retired)
UniversityofArizona,USA MerrittIsland,FL,USA
vanManen,Robbert Roy,Douglas
HealthEconomicsandClinicalOutcomesResearch,Medical DivisionofPathwayMedicine,MedicalSchool,Universityof
Affairs,CentocorInc.,Horsham,PA,USA Edinburgh,Edinburgh,UK
Sands,Robert
Mann,Ronald
Sanofi-aventis,Cambridge,MA,USA
UniversityofSouthampton,Hants,UK
Email:rob.sands@sanofi-aventis.com
Email:[email protected]
Shapiro,DavidA.
Marks,Peter
InterceptPharmaceuticals,SanDiego,CA,USA
PfizerLimited,Sandwich,Kent,UK
Email:[email protected]
Email:Peter.Marks@pfizer.com
Spilker,Bert
Me´try,Jean-Michel(Deceased)
BertSpilkerAssociates,Bethesda,MD,USA
Email:[email protected]
Minor,Michael
ClinicalDevelopmentandAsianVentures,Kendle
Starkey,PaulW.
InternationalInc., Cincinnati,OH,USA
MerckConsumerCare,WhitehouseStation,NJ,USA
Email:[email protected]
Miskin,Barry
DepartmentofSurgery,NovaSoutheasternUniversity,
Starkey,YanYanLi
CollegeofOsteopathicMedicine,FortLauderdale–Davie,
GlaxoSmithKlineConsumerHealthcare,Parsippany,NJ,USA
Florida,USA
Email:[email protected]
Email:[email protected]
Tabusso,Giuliana
Molony,LeslieJ.
Milan,Italy
TransgeneronTherapeutics,Inc.,Gainesville,FL,USA
Email:[email protected]
Email:[email protected]
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Contributors ix
Tilson,HughH. Wells,MarilynJ.
SchoolofPublicHealth,UniversityofNorthCarolina, EastStroudsburgUniversity,EastStroudsburg,PA,USA
ChapelHill,NC,USA
Email:[email protected] Williams,RogerL.
USPharmacopia,Rockville,MD,USA
Townsend,RaymondJ.
ElanPharmaceuticals,SanDiego,CA,USA Wood,KatieP.J.
Email:[email protected] FosterCity,CA,USA
Email:[email protected]
vanTroostenburg,Anne-Ruth
Yasurhara,H.
TakedaGroupR&D,London,UK
TeikyoUniversity,Tokyo,Japan
Email:[email protected]
Young,Michael
Vogel,John
MDYAssociates,Philadelphia,PA,USA
JohnR.VogelAssociatesInc.,Kihei,HI,USA
Email:[email protected]
Email:[email protected]
Walker,Stuart
CentreforMedicinesResearch,InternationalInstitutefor
RegulatoryScience,LondonUK
Email:[email protected]
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Preface to the First Edition
Pharmaceutical medicine is a relatively new, but pastfewyears,amongwhomwehaveparticularly
rapidly growing, academic discipline. As these stressed(!)MichaelDavis,DeborahReece,Hannah
trends continue into the 21st century, pharma- Bradley,LewisDerrick,andHilaryRowe.
ceutical physicians are increasingly regarding con- Lastly,wewouldliketothankourfamilies,and
sultancy work and contract research organization friends, who have withstood the frequent tele-
(CRO)affiliationasgoodcareeropportunities,and phone calls, e-mails, and meetings, often late into
now recognize the need for continuing education thenight.Indeed,toallwhomadethisprojectpos-
andtraininginthisbroadspectrumdiscipline. sible,bothauthorsandnon-authors,wethankyou.
As editors, we would like to thank our contrib- Wearecertainthatthisspecialty,andourpatients,
utorsfortheirexpertise,theirdedication,andtheir even though we may help them vicariously, will
vision. We would like to thank and acknowledge benefitbecauseofyourcontributions.
theworkandcounselofourcolleagueRobertBell,
MD, PhC, who helped us greatly during the early AndrewFletcher
partofthisproject.Wewouldalsoliketothankand LionelEdwards
acknowledge the enormous help, encouragement, TonyFox
andpatienceoftheteamatJohnWiley&Sons,Ltd, PeterStonier
UK,withwhomwehaveworkedcloselyoverthese
x