Coursedescription:Thegoal ofthis courseisto laya solidfoundationonethical,statisticalandlogisticalissuesaboutdesigningandanalyzingclinicaltrials.Theemphasisisonimportantmethodsofdesigningandanalyzingresponseadaptiveclinicaltrials.TopicsincludePhasellltrialrandomization,selectionbias,responseadaptivedesigns andtheirinference,largesampleinference,practicalissuesandopenproblemsPrerequisites:Goodknowledgeonprobabilityandstochasticprocesses,includinglimittheoremsandmartingaleslikelihoodbasedinferenceand asymptoticstatistics.福NIVERSITMANToaXikui Wang (University of Manitoba)Statistical Decision Analysis20134/198
Course description: The goal of this course is to lay a solid foundation on ethical, statistical and logistical issues about designing and analyzing clinical trials. The emphasis is on important methods of designing and analyzing response adaptive clinical trials. Topics include Phase III trial randomization, selection bias, response adaptive designs and their inference, large sample inference, practical issues and open problems. Prerequisites: Good knowledge on probability and stochastic processes, including limit theorems and martingales, likelihood based inference and asymptotic statistics. Xikui Wang (University of Manitoba) Statistical Decision Analysis 2013 4 / 198
Referencebooks:Clinicaltrialdesign-Bayesianandfrequentistadaptivemethods,byG.Yin,JohnWileyandSons,2012Randomizationinclinicaltrials-theoryandpractice,byW.FRosenbergerandJ.M.Lachin,JohnWileyandSons,2o02Thetheoryofresponse-adaptiverandomization inclinicaltrials,byF.HuandW.F.Rosenberger,JohnWileyandSons,2006Introductiontostatisticalmethodsforclinicaltrials,eds.byT.D.CookandD.L.DeMets,ChapmanandHall/CRC,2o08Evaluatingclinicalresearch(2nded.),byB.D.FurbergandC.D. Furberg, Springer, 2007Controversialstatisticalissuesinclinicaltrials,byS-C.Chow,ChapmanandHall,2011福UNIVERSITMANTToaKikui Wang (University of Manitoba)Statistical Decision Analysis20135/198
Reference books: Clinical trial design - Bayesian and frequentist adaptive methods, by G. Yin, John Wiley and Sons, 2012. Randomization in clinical trials - theory and practice, by W.F. Rosenberger and J.M. Lachin, John Wiley and Sons, 2002 The theory of response-adaptive randomization in clinical trials, by F. Hu and W.F. Rosenberger, John Wiley and Sons, 2006 Introduction to statistical methods for clinical trials, eds. by T.D. Cook and D.L. DeMets, Chapman and Hall/CRC, 2008 Evaluating clinical research (2nd ed.), by B.D. Furberg and C.D. Furberg, Springer, 2007 Controversial statistical issues in clinical trials, by S-C. Chow, Chapman and Hall, 2011 Xikui Wang (University of Manitoba) Statistical Decision Analysis 2013 5 / 198
Referencepapers:OX.Wang(2013).Banditprocessesandresponseadaptiveclinicaltrials:theartof explorationversusexploitation.MethodsandApplicationsof Statistics inClinicalTrialsVolume2:Planning,Analysis,andInferentialMethodsX.LiandX.Wang(2013).Responseadaptivedesignswithmisclassifiedresponses.CommunicationsinStatistics-TheoryandMethods42:2071-2083.X.LiandX.Wang(2012).Variance-penalizedresponse-3adaptiverandomization withmismeasurement.JournalofStatisticalPlanningandInference142:2128-2135.Y.Yi and Xikui Wang (2011). Comparison of Wald, score,and likelihoodratiotestsforresponseadaptivedesignsJournalofStatisticalTheoryandApplications10:553-569D.Tolussoand X.Wang (2011).Interval estimation for5responseadaptiveclinicaltrials.ComputationalStatisticsIVERSITLMANITONandDataAnalysis55:725-730.GkuiWang(Universityof Manitoba)Statistical Decision Analysis20136/198
Reference papers: 1 X. Wang (2013). Bandit processes and response adaptive clinical trials: the art of exploration versus exploitation. Methods and Applications of Statistics in Clinical Trials, Volume 2: Planning, Analysis, and Inferential Methods 2 X. Li and X. Wang (2013). Response adaptive designs with misclassified responses. Communications in Statistics - Theory and Methods 42: 2071-2083. 3 X.Li and X. Wang (2012). Variance-penalized responseadaptive randomization with mismeasurement. Journal of Statistical Planning and Inference 142: 2128-2135. 4 Y. Yi and Xikui Wang (2011). Comparison of Wald, score, and likelihood ratio tests for response adaptive designs. Journal of Statistical Theory and Applications 10: 553-569. 5 D. Tolusso and X. Wang (2011). Interval estimation for response adaptive clinical trials. Computational Statistics and Data Analysis 55: 725-730. Xikui Wang (University of Manitoba) Statistical Decision Analysis 2013 6 / 198
Referencepapers:OY.YiandXikuiWang(2009).Responseadaptivedesignswithavariance-penalizedcriterion.BiometricalJournal51:763-773.Y.YiandXikuiWang(2008).Asymptotically efficientestimationinresponseadaptivetrials.Journalof StatisticalPlanningandInference138:2899-2905.Y.YiandXikuiWang(2007).Statisticalinferenceof3adaptivedesignswithbinaryresponses.CommunicationsinStatistics-TheoryandMethods36:1643-1653.Y.YiandXikuiWang(2007).Goodness-of-fittestforresponseadaptivedesigns.StatisticsandProbabilityLetters77:1014-1020.D.PullmanandX.Wang(2001).Adaptivedesigns,5informed consent,and the ethics ofresearch.Controlled鞋UNIVERSITClinicalTrials22:203-210IMANITOSXikuiWang(UniversityofManitoba)Statistical Decision Analysis20137/198
Reference papers: 1 Y. Yi and Xikui Wang (2009). Response adaptive designs with a variance-penalized criterion. Biometrical Journal 51: 763-773. 2 Y. Yi and Xikui Wang (2008). Asymptotically efficient estimation in response adaptive trials. Journal of Statistical Planning and Inference 138: 2899-2905. 3 Y. Yi and Xikui Wang (2007). Statistical inference of adaptive designs with binary responses. Communications in Statistics - Theory and Methods 36: 1643-1653. 4 Y. Yi and Xikui Wang (2007). Goodness-of-fit test for response adaptive designs. Statistics and Probability Letters 77: 1014-1020. 5 D. Pullman and X. Wang (2001). Adaptive designs, informed consent, and the ethics of research. Controlled Clinical Trials 22: 203-210. Xikui Wang (University of Manitoba) Statistical Decision Analysis 2013 7 / 198
医药使人生病Medicinemakespeopleill数学使人悲伤mathematicsmakesthemsadand theology makes them sinful.神学使人有罪MartinLuther(1483-1546)NIVERSITMANITONXikui Wang (University of Manitoba)Statistical Decision Analysis20138/198
Medicine makes people ill, mathematics makes them sad and theology makes them sinful. 医药使人生病 数学使人悲伤 神学使人有罪 Martin Luther (1483 - 1546) Xikui Wang (University of Manitoba) Statistical Decision Analysis 2013 8 / 198