Clinical Trials in Rheumatoid Arthritis and Osteoarthritis

323 Pages·2008·11.6 MB·English

Clinical Trials in Rheumatoid
Arthritis and Osteoarthritis
SeriesEditors
DerekPearson,BSc,PhD ColinG.Miller,PhD,FICR
JointServiceManager SeniorVicePresident
MedicalPhysics&ClinicalEngineering MedicalAffairs
Department Bio-ImagingTechnologiesInc.
NottinghamUniversityHospitalsNHS 826Newtown-YardleyRoad
Trust Newtown,PA18940
CityHospitalsCampus USA
HucknallNG51PB
UK
OtherTitlesinThisSeries
ClinicalTrialsinOsteoporosis(2ndEdition)
DerekPearsonandColinG.Miller
ClinicalTrialsinRheumatoidArthritisandOsteoarthritis
DavidM.ReidandColinG.Miller
•
David M. Reid Colin G. Miller
Editors
Clinical Trials in Rheumatoid
Arthritis and Osteoarthritis
123
Editors
DavidM.Reid,MBChB,MD,FRCP ColinG.Miller,BSc,PhD,FICR
DepartmentofMedicineandTherapeutics Bio-ImagingTechnologiesInc.
UniversityofAberdeen Newtown,PA,USA
Aberdeen,UK
ISBN:978-1-85233-874-9 e-ISBN:978-1-84628-742-8
DOI:10.1007/978-1-84628-742-8
BritishLibraryCataloguinginPublicationData
Clinicaltrialsinrheumatoidarthritisandosteoarthritis
1.Rheumatoidarthritis-Treatment2.Osteoarthritis-
Treatment3.Clinicaltrials
I.Reid,David,1951-II.Miller,ColinG.,1960-
616.7’22060724
ISBN-13:9781852338749
LibraryofCongressControlNumber:2007937490
(cid:2)c2008Springer-VerlagLondonLimited
Apart from any fair dealing for the purposes of research or private study, or criticism or review, as
permittedundertheCopyright,DesignsandPatentsAct1988,thispublicationmayonlybereproduced,
storedortransmitted,inanyformorbyanymeans,withthepriorpermissioninwritingofthepublish-
ers,orinthecaseofreprographicreproductioninaccordancewiththetermsoflicencesissuedbythe
CopyrightLicensingAgency.Enquiriesconcerningreproductionoutsidethosetermsshouldbesentto
thepublishers.
Theuseofregisterednames,trademarks,etc.inthispublicationdoesnotimply,evenintheabsenceofa
specificstatement,thatsuchnamesareexemptfromtherelevantlawsandregulationsandthereforefree
forgeneraluse.
Productliability:Thepublishercangivenoguaranteeforinformationaboutdrugdosageandapplication
thereofcontainedinthisbook.Ineveryindividualcasetherespectiveusermustcheckitsaccuracyby
consultingotherpharmaceuticalliterature.
Printedonacid-freepaper
987654321
SpringerScience+BusinessMedia
springer.com
Contents
Contributors ..................................................... vii
1 Introduction ................................................... 1
DavidM.ReidandColinG.Miller
2 Historical and Current Perspectives on Management of
OsteoarthritisandRheumatoidArthritis.......................... 5
ShirishDubeyandAdewaleO.Adebajo
3 DevelopmentofBiologicalTherapiesforInflammatoryArthritis..... 37
NeilBasu
4 StudyDesignandEndPointsforRheumatoidArthritisTrials ....... 51
PieterGeusensandColinG.Miller
5 Study Design and End Points in Ankylosing Spondylitis
ClinicalTrials.................................................. 69
DésiréevanderHeijde
6 TrialDesignandOutcomesinOsteoarthritis....................... 81
NigelArden
7 EthicalConsiderations .......................................... 91
DerekPearsonandColinG.Miller
8 OrganizationoftheClinicalTrialbytheSponsor ..................113
ColinG.Miller
9 OrganizationoftheTrialattheInvestigatorSite ...................123
JulieShotton,DavidM.Reid,andColinG.Miller
10 RoleoftheImagingCoreLaboratoryinRheumatoidArthritisand
OsteoarthritisClinicalTrials.....................................135
MarkD.EndresandAnnaM.Baratelle
11 BiochemicalMarkersofRheumatoidArthritisandOsteoarthritis:
ClinicalUtilityandPracticalConsiderations.......................151
MarioR.EhlersandElizabethT.Leary
v
vi Contents
12 DataAnalysisandPresentation:WritingaPaperforPublication ....171
DerekPearson
13 RadiographicImagingEndPointsinRheumatoidArthritisTrials....201
AnnaM.BaratelleandDésiréevanderHeijde
14 RadiographyinClinicalTrialsInvestigatingOsteoarthritis..........223
CornelisvanKuijk
15 Use of Quantitative Magnetic Resonance Imaging in the
Cross-SectionalandLongitudinalEvaluationofStructuralChanges
inKneeOsteoarthritisPatients...................................235
Jean-Pierre Raynauld, Johanne Martel-Pelletier, François Abram,
andJean-PierrePelletier
16 BiochemicalMarkersasSurrogateEndPointsofJointDisease ......249
L.StefanLohmanderandDavidR.Eyre
17 RoleofGeneticsandGenomicsinClinicalTrialsinOsteoarthritis
andRheumatoidArthritis .......................................275
StuartH.Ralston
18 Cost-Effectiveness of New Biologics for Rheumatoid Arthritis
andOsteoarthritis ..............................................289
YolandaBravoVergelandDavidTorgerson
Abbreviations......................................................309
Index .............................................................311
Contributors
AdewaleO.Adebajo,MBBS,MSc,FRCP
HonorarySeniorLecturer,AcademicRheumatologyGroup,UniversityofSheffield,
SheffieldUK
FrançoisAbram,PhD
ArthroVisionInc.,Montreal,Canada
NigelArden,MBBS,MSc,MD
Senior Lecturer in Rheumatology, MRC Unit, Southampton General Hospital,
Southampton,UK
AnnaM.Baratelle,ASRT,(R)(MR)
Clinical Imaging Lead, Centocor, Malvern, Pennsylvania, USA. Previously,
Director, Business Development and Clinical Education, Bio-Imaging
Technologies,Inc.,Newtown,Pennsylvania,USA
NeilBasu,MBChB(Hons),MRCP(UK)
SpecialistRegistrar,NHSGrampian,AberdeenRoyalInfirmary,Aberdeen,UK
YolandaBravoVergel,BA,MA,MSc
ResearchFellow,CentreforHealthEconomics,UniversityofYork,York,UK
ShirishDubey,MB,BS,MRCP(Ireland),DMedEd
PreviouslyClinicalLecturerinRheumatologyandMedicalEducation,Academic
UnitofMedicalEducation,UniversityofSheffield,Sheffield,UK
MarioR.Ehlers,MD,PhD
ChiefMedicalOfficer,PacificBiometrics,Inc.,Seattle,Washington,USA
MarkD.Endres,BS,CNMT
VicePresident,GlobalBusinessDevelopment,Bio-ImagingTechnologies,Inc.,
Newtown,Pennsylvania,USA
DavidR.Eyre,BS,PhD
Department of Orthopaedics and Sports Medicine, University of Washington,
Seattle,Washington,USA
PieterGeusens,MD,PhD
DepartmentofRheumatology,UniversityHospital,Maastricht,TheNetherlands
andBiomedicalResearchInstitute,UniversityHasselt,Diepenbeek,Belgium
vii
viii Contributors
ElizabethT.Leary,PhD
ChiefScientificOfficer,PacificBiometrics,Inc.,Seattle,Washington,USA
L.StefanLohmander,MD,PhD
Institute of Clinical Sciences, Department of Orthopaedics, Lund University
Hospital,Lund,Sweden
JohanneMartel-Pelletier,PhD
Osteoarthritis Research Unit, Notre-Dame Hospital, University of Montreal
HospitalCentre(CHUM),Montreal,Canada
ColinG.Miller,BSc,PhD,FICR
SeniorVicePresident,MedicalAffairs,Bio-ImagingTechnologiesInc.,Newtown,
Pennsylvania,USA
DerekPearson,BSc,PhD
ClinicalDirector,MedicalPhysics,CityHospital,Nottingham,UK
Jean-PierrePelletier,MD
Osteoarthritis Research Unit, Notre-Dame Hospital, University of Montreal
HospitalCentre(CHUM),Montreal,Canada
StuartH.Ralston,MD,FRCP,FMedSci,FRSE
HeadofSchoolofMolecularandClinicalMedicine&ProfessorofRheumatology,
MolecularMedicineCentre,UniversityofEdinburgh,Edinburgh,UK
Jean-PierreRaynauld,MD,FRCPC
Osteoarthritis Research Unit, Notre-Dame Hospital, University of Montreal
HospitalCentre(CHUM),Montreal,Canada
DavidM.Reid,MBChB,MD,FRCPedin,FRCPlon
Professor of Rheumatology, Head of Department of Medicine & Therapeutics,
UniversityofAberdeen,Aberdeen,UK
JulieShotton,BSc
PreviouslySeniorResearchNurse,OsteoporosisResearchUnit,Departmentof
Medicine&Therapeutics,UniversityofAberdeen,Aberdeen,UK
DavidTorgerson,MSc,PhD
DirectorofYorkTrialsUnit,DepartmentofHealthSciences,UniversityofYork,
York,UK
DésiréevanderHeijde,MD,PhD
Professor of Rheumatology, Leiden University Medical Center, Department
ofRheumatology,Leiden,TheNetherlands
CornelisvanKuijk,MD,PhD
DepartmentofRadiology,VUUniversityMedicalCenter,Amsterdam,
TheNetherlands
Chapter1
Introduction
DavidM.ReidandColinG.Miller
Why a Book About Clinical Trials in Rheumatoid Arthritis
andOsteoarthritis?
From an etiology of disease perspective, a book on rheumatoid arthritis (RA) and
osteoarthritis(OA)isastrangecombination;however,fromaclinicaltrialperspec-
tive,theprimaryendpointsareverysimilar.Theprimaryendpointsinbothdisease
states are imaging and serum or urine biomarkers as recognized by the U.S. Food
andDrugAdministration(FDA)TheFDAguidancedocumentsforOA[1]referto
the RA guidance documents for the imaging end points [2]. During the writing of
thisbook,theOsteoarthritisResearchSocietyInternational(OARSI)hasteamedup
withtheOutcomesMeasuresandEvaluationinRheumatoidArthritisClinicalTrials
(OMERACT)tocreatetheOMERACT-OARSIworkinggroup.Thisisanobvious
recognitionofsimilarendpointsofthediseasestates.
TheevolutionofthetrialsinRAandOAisataninterestingpointintime.There
have been a number of successful therapeutic disease-modifying agents that have
been developed and are now on the market for RA. The same is not true for OA,
where at the time of writing there have been no successful FDA submissions for
a disease modifying osteoarthritis anti-rheumatic drug (DMOARD), partly due to
a lack of compounds and partly due to the challenges of running the trials. With
RA,thereisnowastandardpatternandexpectationforperformingthesetrialswith
threeanti-TNF-(cid:2)andoneanti-B-cellmonoclonalantibodyproductsonthemarket
in a number of indications and many more to follow. For OA, the one large trial
testingapotentialDMOAD,usingthebisphosphonaterisedronate[3],sadlymissed
its primary end point. There are now a handful of studies evaluating glucosamine
andchondroitinsulfateinboththeUnitedStatesandEurope[4,5].Thefirstresults
are not only suggestive of a potential positive outcome but also more importantly
demonstratethatwithcarefulcontrols,astudyinOAlookingatjointspacenarrow-
ingcanbeachieved(seeChapter14).
D.M.Reid
Professor of Rheumatology, Head of Department of Medicine & Therapeutics, University of
Aberdeen,Aberdeen,UK
D.M.Reid,C.G.Miller(eds.),ClinicalTrialsinRheumatoidArthritisandOsteoarthritis, 1
(cid:2)c Springer-VerlagLondonLimited2008