ebook img

Proceedings of the Fourth Seattle Symposium in Biostatistics: Clinical Trials PDF

244 Pages·2013·2.488 MB·English
Save to my drive
Quick download
Download
Most books are stored in the elastic cloud where traffic is expensive. For this reason, we have a limit on daily download.

Preview Proceedings of the Fourth Seattle Symposium in Biostatistics: Clinical Trials

Lecture Notes in Statistics-Proceedings 1205 Editedby P.Bickel P.J.Diggle S.E.Fienberg U.Gather I.Olkin S.Zeger Forfurthervolumes: http://www.springer.com/series/8440 Thomas R. Fleming • Bruce S. Weir Editors Proceedings of the Fourth Seattle Symposium in Biostatistics: Clinical Trials 123 Editors ThomasR.Fleming BruceS.Weir DepartmentofBiostatistics DepartmentofBiostatistics UniversityofWashington UniversityofWashington Seattle,WA98195-7232,USA Seattle,WA98195-7232,USA ISSN1869-7240 ISBN978-1-4614-5244-7 ISBN978-1-4614-5245-4(eBook) DOI10.1007/978-1-4614-5245-4 SpringerNewYorkHeidelbergDordrechtLondon LibraryofCongressControlNumber:2012952276 ©SpringerScience+BusinessMediaNewYork2013 Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewholeorpartof thematerialisconcerned,specificallytherightsoftranslation,reprinting,reuseofillustrations,recitation, broadcasting,reproductiononmicrofilmsorinanyotherphysicalway,andtransmissionorinformation storageandretrieval,electronicadaptation,computersoftware,orbysimilarordissimilarmethodology nowknownorhereafterdeveloped.Exemptedfromthislegalreservationarebriefexcerptsinconnection with reviews or scholarly analysis or material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher’slocation,initscurrentversion,andpermissionforusemustalwaysbeobtainedfromSpringer. PermissionsforusemaybeobtainedthroughRightsLinkattheCopyrightClearanceCenter.Violations areliabletoprosecutionundertherespectiveCopyrightLaw. Theuseofgeneraldescriptivenames,registerednames,trademarks,servicemarks,etc.inthispublication doesnotimply,evenintheabsenceofaspecificstatement,thatsuchnamesareexemptfromtherelevant protectivelawsandregulationsandthereforefreeforgeneraluse. While the advice and information in this book are believed to be true and accurate at the date of publication,neithertheauthorsnortheeditorsnorthepublishercanacceptanylegalresponsibilityfor anyerrorsoromissionsthatmaybemade.Thepublishermakesnowarranty,expressorimplied,with respecttothematerialcontainedherein. Printedonacid-freepaper SpringerispartofSpringerScience+BusinessMedia(www.springer.com) Preface Continuing the tradition, once every half decade, of hosting a major biostatistical meeting, where thought leaders can gather to address scientific issues of current andcompellingimportance,theorganizingcommitteeandsponsorsheldtheFourth Seattle Symposium on Biostatistics on November 22 and 23, 2010. The topic area for this successful meeting was clinical trials, with focus on the use of biomarkers,issues in multi-regionalclinical trials, and identifying and addressing safetysignals.TheeventwassponsoredbyAxioResearch,Bristol-MyersSquibb, Genentech,NovartisandOnyxandwasco-sponsoredbytheUWSchoolofPublic Health and the Division of Public Health Sciences at the Fred HutchinsonCancer Research Center (FHCRC). The symposium featured keynote lectures by Robert O’Neill,RossPrenticeandRobertTemple,aswellasinvitedtalksbyJesseBerlin, Christy Chuang-Stein,David DeMets, Bill DuMouchel,Susan Ellenberg,Thomas Fleming, Laurence Freedman, Margaret Pepe, Steve Self, Richard Simon, Bruce Weir, John Whittaker and Janet Wittes. Invited panelists included Jesse Berlin, BruceBinkowitz,ChristyChuang-Stein,BillDuMouchel,SusanEllenberg,Thomas Fleming,HenryFuchs,DominicLabriola,RobertO’Neill,RobertTempleandJanet Wittes. There were 200 attendees at the symposium. In addition, more than 100 people attended short courses delivered on November 20 and 21, 2010. At these shortcourses,“StatisticalDesignofSequentialClinicalTrialsinR”wastaughtby ScottEmersonandDanGillen,“TheUseofGeneticMarkerDatainClinicalTrials” wastaughtbyBruceWeirandPatrickHeagerty,“DataMonitoringCommittees:A Practical Approach” was taught by Susan Ellenberg, Thomas Fleming and David DeMets, “Statistical Evaluationof Markers for Classification and Prediction”was taught by Margaret Pepe and “Practice Issues in the Conduct and Reporting of Large-ScaleClinicalTrials:TheWomen’sHealthInitiativeExperience”wastaught byGarnetAndersonandAndreaLeCroix. When the UW School of Public Health was formed in 1970, biostatistics as a discipline was veryyoung.In the subsequent40 years, boththe field and the UW Department of Biostatistics have evolved in many exciting ways. The department had only seven faculty when it moved from the School of Medicine to the new School of Public Health and Community Medicine in 1970. The faculty roster v vi Preface currentlylists 49 regular and research faculty and 34 adjunctand affiliate faculty. Ed Perrin was the Department Chair in 1970, succeeded by Donovan Thompson, Norman Breslow, Thomas Fleming and presently Bruce Weir. The faculty have beenactivelyinvolvedin methodologicalandcollaborativeresearchin additionto graduateteaching.ThechoiceofClinicalTrialsasthethemefortheFourthSeattle SymposiuminBiostatisticswasatributetothesignificantcontributionsmadebythe UWandFHCRCfacultytothisimportantareaofstatisticalscience. The Symposium Organizing Committee consisted of Susan Ellenberg, Scott Emerson, Nathalie Ezzet, Thomas Fleming (Chair), Henry Fuchs, Lee Hooks, DominicLabriola,MichaelOstland,RossPrenticeandBruceWeir.Thestaffofthe DepartmentofBiostatistics,especiallySandraCoke,providedgreatadministrative supporttothesymposium.TheUWSchoolofPublicHealthDeanHowardFrumkin, the Department Chair Bruce Weir and the Organizing Committee Chair Thomas Fleming delivered the opening remarks. The scientific sessions were chaired by Bruce Weir, Scott Emerson, Thomas Fleming, Lee Hooks, Henry Fuchs, Michael Ostland,SusanEllenberg,NathalieEzzetandDominicLabriola.Wearegratefulto the aforementionedpeople as well as all the speakersand participantsfor making thesymposiumagreatsuccess. Thisvolumecontainsmostofthepaperspresentedatthesymposium,aswellas someofthesciencepresentedattheshortcourses.Thesepapersencompassrecent methodologicaladvancesonseveralimportanttopics,summariesofthestateofthe artofmethodologyinkeyareasofclinicaltrials,aswellasinnovativeapplications ofthe existingtheoryandmethods.Thiscollectionservesas a referenceforthose workinginseveralkeyareasofclinicaltrials. Eachofthe12papersinthisvolumewasreferredbytwoorthreepeerreviewers, andtheircommentswereincorporatedbytheauthorsintothefinalversionsofthe papers. The referees are listed at the end of this book. We are indebted to them fortheirtimeandefforts.We alsoappreciatetheguidanceandassistancebyMarc SpringerofSpringer-Verlag. Contents Preface............................................................................. v PartI Biomarkers:RoleintheDesignandInterpretation ofClinicalTrials The RoleandPotentialofSurrogateOutcomesinClinical Trials:HaveWeMadeAnyProgressinthePastDecade?................... 3 DavidL.DeMets OntheUseofBiomarkerstoElucidateClinicalTrialResults: ExamplesfromtheWomen’sHealthInitiative ............................... 21 RossL.PrenticeandShanshanZhao OntheUseofBiomarkersinVaccineResearchandDevelopment......... 35 StevenG.Self PartII Biomarkers:IssuesinIndividualizedTherapy RecentDevelopmentsintheUseofClinicalTrialstoSupport IndividualizingTherapies:ARegulatoryPerspective ....................... 49 RobertT.O’Neill OncologyClinicalTrialsintheGenomicEra................................. 63 RichardSimonandJyothiSubramanian UsingSNPstoCharacterizeGeneticEffectsinClinicalTrials.............. 81 B.S.Weir PartIII IssuesinMulti-RegionalClinicalTrials WhyIsThisSubgroupDifferentfromAllOtherSubgroups? ThoughtsonRegionalDifferencesinRandomizedClinicalTrials ......... 95 JanetWittes vii viii Contents PartIV Safety QuantitativeRisk/BenefitAssessment:WhereAreWe?..................... 119 ChristyChuang-Stein IdentifyingandAddressingSafetySignalsinClinicalTrials: SomeIssuesandChallenges .................................................... 137 ThomasR.Fleming Past,Present,andFutureofDrugSafetyAssessment ....................... 157 RobertTemple PartV SpecialTopics Designing, Monitoring,and Analyzing GroupSequential ClinicalTrialsUsingtheRCTdesignPackageforR ........................ 177 DanielL.GillenandScottS.Emerson GeneticMarkersinClinicalTrials............................................. 209 B.S.WeirandP.J.Heagerty AddressesforContactAuthors(inthesameorderasthepapers).......... 247 Part I Biomarkers: Role in the Design and Interpretation of Clinical Trials The Role and Potential of Surrogate Outcomes in Clinical Trials: Have We Made Any Progress in the Past Decade? DavidL.DeMets Abstract Randomized clinical trials are the standard method for evaluating new interventionsorcomparingexistingones.Trialswhichuseclinicaloutcomesasthe primary outcome can be large, require lengthy follow-up, and can be expensive. For these reasons, researchers have sought to use intermediate outcomes such as biomarkersasasubstituteorsurrogatefortheclinicaloutcome.Overadecadeago, thispracticehadbecomecommon.FlemingandDeMets(AnnInternMed125:605– 613,1996)reportedmanycaseswheretheuseofabiomarkerasasurrogateoutcome failedtoreliablyassesstheeffectoftheintervention,insomecasesmissingharmful effectsincludingmortality.Recently,theInstituteofMedicine(IOM)reviewedthe state oftheartandcametosimilarconclusionsthatbiomarkershaveoftenproved to be unreliable as a surrogate [Committee on Qualifications of Biomarkers and SurrogateEndpointsinChronicDisease,MichaelC,BallJ(eds)(2010)Evaluation of biomarkers and surrogate endpoints in chronic disease. National Academies Press, Washington]. They proposed that biomarkers must meet certain criteria including analytic validity, strong correlation with the clinical outcome and the ability to capture the full effects of the intervention. The use of a biomarker as a surrogate must be done so in the context of its intended use, and done so with greatcaution.WhiletheIOMreportfurtherclarifiesthenecessaryrequirementsof a potentialbiomarkeras a surrogate, the reportstill recommendscaution in using surrogate outcomes in final phases of intervention evaluation as did Fleming and DeMets(AnnInternMed125:605–613,2004). D.L.DeMets((cid:2)) DepartmentofBiostatistics&MedicalInformatics,UniversityofWisconsin-Madison, 610WalnutStreet,Madison,WI,53726USA e-mail:[email protected] T.R.FlemingandB.S.Weir(eds.),ProceedingsoftheFourthSeattleSymposium 3 inBiostatistics:ClinicalTrials,LectureNotesinStatistics1205, DOI10.1007/978-1-4614-5245-4 1,©SpringerScienceCBusinessMediaNewYork2013

See more

The list of books you might like

Most books are stored in the elastic cloud where traffic is expensive. For this reason, we have a limit on daily download.