Predictive biomarker enrichment designs in Phase II clinical trials
|
|
- Roy Flowers
- 5 years ago
- Views:
Transcription
1 Predictive biomarker enrichment designs in Phase II clinical trials Deepak Parashar and Nigel Stallard Statistics and Epidemiology Unit Warwick Medical School 05 June 2018 Deepak Parashar 05 June /16
2 Fixed Enrichment Designs Assess biomarker in F = (S, S) Biomarker + (S) Biomarker ( S) Trial Design (Single-arm/Randomise etc.) Off Study Goal: Hypothesis test in biomarker + subgroup S only. Issue: No comparator test in the complementary subgroup S. Is the biomarker predictive? Deepak Parashar 05 June /16
3 Adaptive Enrichment Designs Stage 1: Enrol F Interim Stage 2 STOP Enrich S Continue F Goal: Hypotheses test in S and F. Issue: While S is included in F, no explicit testing in S. Is the biomarker predictive? Deepak Parashar 05 June /16
4 Biomarker ve: To test or not to test? FDA Concerns 1 Design may not be efficient if drug has at least some activity in biomarker ve patients. 2 Effect in biomarker ve patients may never be known. 3 Study would provide no new clinical evidence w.r.t. biomarker ve patients. 4 Implications for Phase III Need for testing in biomarker + and biomarker ve subgroup Deepak Parashar 05 June /16
5 Example: Simon two-stage enrichment design Phase II targeted cancer therapy Determine whether drug has activity only in target population or the general population Outcome is (RECIST) tumour response Single-arm trial Enrichment adaptation (with testing in Biomarker ve) based on Simon two-stage design Jones et. al., Contemp. Clin. Trials 2007 Parashar et. al., Pharmaceut. Statistics 2016 Deepak Parashar 05 June /16
6 Hypotheses (Group-sequential) H 0 : p = p 0, H+ 0 : p+ = p + 0 H 1 : p = p 1, H+ 1 : p+ = p + 1 Assume p < p + Conclude efficacy in full population if we reject H 0 Conclude efficacy in biomarker positive if we reject H + 0 Deepak Parashar 05 June /16
7 Design Schematic Recruit Unselected (N 1, N 1 + ) Go decision Unselected (X 1 k ) Sufficient Response Unselected (X 1 k 1 ) Insufficient Response Unselected (X 1 < k 1 ) Route 1 Go decision Positives (X 1 + k e + ) Sufficient Response Positives (X 1 + k 1 + ) Insufficient Response Positives STOP Route 3 Stage 2 Stage 2 Enrichment Recruit Unselected (N 2, N 2 + ) Recruit Positives (N 2e + ) Go decision Unselected (X k ) Route 1 Cumulative Response Unselected (X < k ) Go decision Positives (X e + k e + ) Route 3 No-Go decision Route 2 Go decision Positives (X + k + ) No-Go decision Deepak Parashar 05 June /16
8 Question: Is the biomarker truly predictive? Suggestion: Randomised Clinical Trial testing in targeted and non-targeted subpopulations! Deepak Parashar 05 June /16
9 Notation h E h C θ S θ S HR S HR S hazard using the experimental drug hazard using the control drug log ( he S ) /hs C ) log (h S E /h S C hazard ratio of S hazard ratio of S HR S HR S θ < 0 experimental treatment more efficient than control θ 0 no improvement with experimental treatment Deepak Parashar 05 June /16
10 Randomised Enrichment Design for TTE Endpoints Enrol (S, S) Test H S : θ S 0 in S E better than C in S E not better than C in S Test H S : θ S 0 Stage 2:Enrol (S, S) in both arms Stop for futility E better than C in S E better than C in S Go Decision (S, S) E not better than C in S Stage2: Enrich S in both arms No further testing Go Decision S Go Decision S No further testing Deepak Parashar 05 June /16
11 Mehta et.al. (Statist. Med. 2014) Key points Based on CER approach (Müller and Schäfer) guarantees strong control of Type 1 error rate. Permits utilisation of all interim data. Hypotheses testing in subgroups S and S instead of F and S. Conditioning event at interim: pair of future logrank test statistic after observing events in S and S Irle and Schäfer: critical value for testing H S satisfies the CRP principle, and guarantees stochastic independence of the logrank test statistic. Triple (k, T, c) (Events, Logrank test statistic, Critical value for T to reject null) Deepak Parashar 05 June /16
12 Methodology Sketch (à la Mehta) Enrol (S, S) Interim: (k S I, T S I, c S I ), (k S I, T S I, c S I ) Stage 2: Continue (S, S) Stage 1 events continuing (incl. censored) Enrich S Planned / Final:(k S, T S, c S ) (k S I (k S I, T S I, T S I, c S I ), c S I ) (k S e, T S e, c S e ) Actual Analysis:( k S, T S, c S ) ( k I S, T I S, c I S) ( k S I, T S I, c S I ) ( k S e, T S e, c S e ) Go Decision (S, S) Go Decision S Go Decision S Deepak Parashar 05 June /16
13 CRP Principle Go Decision S Reject H S if T S e > c S e s.t. P( T e S > c e S T I S ) + P( }{{} T S > c S T I S ) }{{} enrichment non enrichment P(Te S > ce S T S I ) + P(T S > c S T S I ) }{{} fixeddesign Go Decision (S, S) Reject H S if T S > c S s.t. P( T S > c S T S I ) P(T S > c S T S I ) CER of 2-stage design bounded by the error rates of fixed design Deepak Parashar 05 June /16
14 Non-small cell lung cancer trial Clinical Setting: endpoint: Progression-free Survival sample size: 160 patients accrual rate: 15 patients/month interim analysis - after recruitment of 40 patients from each subgroup Target Hazard Ratio: HR S = 0.5 Biomarker prevalence rate: {0.30, 0.35, 0.40, 0.45} Familywise error rate: α = 0.05 Power: 1 β = 0.80 HR S HR S Deepak Parashar 05 June /16
15 Probability of concluding efficacy (HR S = 0.5) Close to the desired power in all cases a trial of 160 patients should provide sufficient evidence of efficacy in the biomarker-positive group. Deepak Parashar 05 June /16
16 Conclusions Efficient when HR S is small (0.5 to 0.6) and HR S is large (0.8 to 1): Predictive biomarker Obtain desired power for recommending an enriched Phase III trial. Copes well with slower recruitment rate as well as varying prevalence rates. Warwick - Roche MRC icase PhD Student starting Sept Deepak Parashar 05 June /16
17 Conclusions Efficient when HR S is small (0.5 to 0.6) and HR S is large (0.8 to 1): Predictive biomarker Obtain desired power for recommending an enriched Phase III trial. Copes well with slower recruitment rate as well as varying prevalence rates. Warwick - Roche MRC icase PhD Student starting Sept Deepak Parashar 05 June /16
The Roles of Short Term Endpoints in. Clinical Trial Planning and Design
The Roles of Short Term Endpoints in Clinical Trial Planning and Design Christopher Jennison Department of Mathematical Sciences, University of Bath, UK http://people.bath.ac.uk/mascj Roche, Welwyn Garden
More informationNCIC CTG New Investigators Course: Workshop II. Dongsheng Tu and Penelope Bradbury August 21-23, 2013
NCIC CTG New Investigators Course: Workshop II Dongsheng Tu and Penelope Bradbury August 21-23, 2013 Objectives Review practical aspects of the design of the phase II trial Discuss statistical considerations
More informationStatistical Challenges in Immunotherapy: Non Proportional Hazard Model. BBS / PSI CIT event 15-June-2017, Basel Claude BERGE, Roche
Statistical Challenges in Immunotherapy: Non Proportional Hazard Model BBS / PSI CIT event 15-June-2017, Basel Claude BERGE, Roche 1 Statistical Challenges Biomarker Efficacy Endpoint Study Design & Analysis
More informationAccelerating Phase II-III Oncology Drug Development Through the Use of Adaptive Designs
Accelerating Phase II-III Oncology Drug Development Through the Use of Adaptive Designs - Jonathan R. Smith, Ph.D. June 15th, 2004, DIA Annual Meeting, Washington Outline of Presentation Oncology Background
More informationPopulation Enrichment Designs Case Study of a Large Multinational Trial
Population Enrichment Designs Case Study of a Large Multinational Trial Harvard Schering-Plough Workshop Boston, 29 May 2009 Cyrus R. Mehta, Ph.D Cytel Corporation and Harvard School of Public Health email:
More informationIncorporating the direct assignment option into broader design frameworks
Incorporating the direct assignment option into broader design frameworks Ming-Wen An Sumithra J. Mandrekar, Daniel J. Sargent Lucy Lu Martin J. Edelman Vassar College, Poughkeepsie NY Mayo Clinic, Rochester
More informationCHL 5225 H Advanced Statistical Methods for Clinical Trials. CHL 5225 H The Language of Clinical Trials
CHL 5225 H Advanced Statistical Methods for Clinical Trials Two sources for course material 1. Electronic blackboard required readings 2. www.andywillan.com/chl5225h code of conduct course outline schedule
More information(Regulatory) views on Biomarker defined Subgroups
(Regulatory) views on Biomarker defined Subgroups Norbert Benda Disclaimer: Views expressed in this presentation are the author's personal views and not necessarily the views of BfArM Biomarker defined
More informationFundamental Clinical Trial Design
Design, Monitoring, and Analysis of Clinical Trials Session 1 Overview and Introduction Overview Scott S. Emerson, M.D., Ph.D. Professor of Biostatistics, University of Washington February 17-19, 2003
More informationPhase II trial designs and endpoints
Eti Estimating anti-tumour tit activity it Phase II trial designs and endpoints Margaret Hutka MD PhD The Royal Marsden Hospital GI & Lymphoma Unit London, UK margaret.hutka@rmh.nhs.uk www.royalmarsden.nhs.uk
More informationMedia Release. Basel, 17 May 2018
Media Release Basel, 17 May 2018 Phase III IMpower150 study showed Roche s Tecentriq and Avastin plus carboplatin and paclitaxel helped people with a specific type of metastatic lung cancer live significantly
More informationClinical Trial Design to Expedite Drug Development Mary W. Redman, Ph.D.
Clinical Trial Design to Expedite Drug Development Mary W. Redman, Ph.D. What do we mean by expediting drug development? Phase I Single Arm Phase II (expansion cohort) Randomized Phase II Phase III Necessary?
More informationAccelerating Innovation in Statistical Design
Implementing a National Cancer Clinical Trials System for the 21 st Century, Workshop #2 Session #5: Accelerating Innovation Through Effective Partnerships Accelerating Innovation in Statistical Design
More informationMultiplicity and other issues related to biomarker-based oncology trials ASA NJ Chapter
Multiplicity and other issues related to biomarker-based oncology trials ASA NJ Chapter Keaven M. Anderson, Christine K. Gause, Cong Chen Merck Research Laboratories November 11, 2016 With thanks to Eric
More information3. Fixed-sample Clinical Trial Design
3. Fixed-sample Clinical Trial Design Review of course organization 1. Scientific Setting 1.1 Introduction and overview 1.2 Phases of investigation 1.3 Case Study 2. From scientific setting to statistical
More informationSUPPLEMENTARY MATERIAL
SUPPLEMENTARY MATERIAL Supplementary Figure 1. Recursive partitioning using PFS data in patients with advanced NSCLC with non-squamous histology treated in the placebo pemetrexed arm of LUME-Lung 2. (A)
More informationMedia Release. Basel, 18 February 2017
Media Release Basel, 18 February 2017 Phase II study supports potential for Roche s TECENTRIQ (atezolizumab) plus Avastin (bevacizumab) for people with locally advanced or metastatic renal cell carcinoma
More informationBayesian Methods in Regulatory Science
Bayesian Methods in Regulatory Science Gary L. Rosner, Sc.D. Regulatory-Industry Statistics Workshop Washington, D.C. 13 September 2018 What is Regulatory Science? US FDA Regulatory Science is the science
More informationMedia Release. Basel, 26 March 2018
Media Release Basel, 26 March 2018 Phase III IMpower150 study showed Roche s TECENTRIQ (atezolizumab) and Avastin (bevacizumab) plus carboplatin and paclitaxel helped people with advanced lung cancer live
More informationCurrent Issues in Clinical Trials A Biostatistician s perspective
Current Issues in Clinical Trials A Biostatistician s perspective Centra de Recerca Matematica CRM Seminar 10 September 2015 BARCELONA CATALUNYA Urania Dafni National and Kapodistrian University of Athens
More informationPhase II Design. Kim N. Chi NCIC/NCIC-CTG NEW INVESTIGATORS CLINICAL TRIALS COURSE
Phase II Design Kim N. Chi NCIC/NCIC-CTG NEW INVESTIGATORS CLINICAL TRIALS COURSE Phase II Study Results Phase II Study Results Agenda Objectives of phase II trials Endpoints of phase II trials Statistical
More informationDecision Making in Confirmatory Multipopulation Tailoring Trials
Biopharmaceutical Applied Statistics Symposium (BASS) XX 6-Nov-2013, Orlando, FL Decision Making in Confirmatory Multipopulation Tailoring Trials Brian A. Millen, Ph.D. Acknowledgments Alex Dmitrienko
More informationDesign for Targeted Therapies: Statistical Considerations
Design for Targeted Therapies: Statistical Considerations J. Jack Lee, Ph.D. Department of Biostatistics University of Texas M. D. Anderson Cancer Center Outline Premise General Review of Statistical Designs
More informationNEED A SAMPLE SIZE? How to work with your friendly biostatistician!!!
NEED A SAMPLE SIZE? How to work with your friendly biostatistician!!! BERD Pizza & Pilots November 18, 2013 Emily Van Meter, PhD Assistant Professor Division of Cancer Biostatistics Overview Why do we
More informationPanitumumab: The KRAS Story. Chrissie Fletcher, MSc. BSc. CStat. CSci. Director Biostatistics, Amgen Ltd
Panitumumab: The KRAS Story Chrissie Fletcher, MSc. BSc. CStat. CSci. Director Biostatistics, Amgen Ltd Clinical Background: panitumumab in mcrc Panitumumab is a fully human IgG2 monoclonal antibody directed
More informationAdaptive Treatment Arm Selection in Multivariate Bioequivalence Trials
Adaptive Treatment Arm Selection in Multivariate Bioequivalence Trials June 25th 215 Tobias Mielke ICON Innovation Center Acknowledgments / References Presented theory based on methodological work regarding
More informationDesign and analysis of clinical trials
Design and analysis of clinical trials Lecture 3 1.Basic Design Considerations 2.Sample Size determinationa 3.Randomization 2018-01-31 Previous Lectures Definition of a clinical trial The drug development
More informationStatistical, clinical and ethical considerations when minimizing confounding for overall survival in cancer immunotherapy trials
Statistical, clinical and ethical considerations when minimizing confounding for overall survival in cancer immunotherapy trials Dominik Heinzmann, PhD Global Development Team Leader HER2 Associate Director
More informationEGFR inhibitors in NSCLC
Suresh S. Ramalingam, MD Associate Professor Director of Medical Oncology Emory University i Winship Cancer Institute EGFR inhibitors in NSCLC Role in 2nd/3 rd line setting Role in first-line and maintenance
More informationInterim Futility Monitoring When Assessing Immune Therapies With A Potentially Delayed Treatment Effect
Interim Futility Monitoring When Assessing Immune Therapies With A Potentially Delayed Treatment Effect Boris Freidlin Edward Korn National Cancer Institute Bethesda, MD Motivation Introduction of new
More informationSample-size re-estimation in Multiple Sclerosis trials
Novartis Basel, Switzerland Sample-size re-estimation in Multiple Sclerosis trials Heinz Schmidli PSI Meeting on Sample Size Re-Estimation London, November 2, 2016 Outline Multiple Sclerosis Sample size
More informationMedia Release. Basel, 7 May 2018
Media Release Basel, 7 May 2018 FDA grants priority review to Roche s cancer immunotherapy TECENTRIQ (atezolizumab) for initial treatment of people with a specific type of metastatic lung cancer Roche
More informationFrequentist Evaluation of Group Sequential Clinical Trial Designs
UW Biostatistics Working Paper Series 3-9-2005 Frequentist Evaluation of Group Sequential Clinical Trial Designs Scott S. Emerson University of Washington, semerson@u.washington.edu John M. Kittelson University
More informationDesign considerations for Phase II trials incorporating biomarkers
Design considerations for Phase II trials incorporating biomarkers Sumithra J. Mandrekar Professor of Biostatistics, Mayo Clinic Pre-Meeting Workshop Enhancing the Design and Conduct of Phase II Studies
More informationUse of Single-Arm Cohorts/Trials to Demonstrate Clinical Benefit for Breakthrough Therapies. Eric H. Rubin, MD Merck Research Laboratories
Use of Single-Arm Cohorts/Trials to Demonstrate Clinical Benefit for Breakthrough Therapies Eric H. Rubin, MD Merck Research Laboratories Outline Pembrolizumab P001 study - example of multiple expansion
More informationNegative Trials in RCC: Where Did We Go Wrong? Can We Do Better?
Negative Trials in RCC: Where Did We Go Wrong? Can We Do Better? 9 th European Kidney Cancer Symposium, Dublin, April 2014 Tim Eisen Tim Eisen - Disclosures Company Research Support Advisory Board Trial
More informationMedia Release. Basel, 07 December 2017
Media Release Basel, 07 December 2017 Phase III IMpower150 study showed Tecentriq (atezolizumab) and Avastin (bevacizumab) plus chemotherapy reduced the risk of disease worsening or death by 38 percent
More informationRandomized Clinical Trials
Randomized Clinical Trials p. 1/42 Randomized Clinical Trials Hematology/Oncology Lecture Series Elizabeth G. Hill, PhD Associate Professor of Biostatistics 17 November 2011 Randomized Clinical Trials
More informationMedia Release. Basel, 21 July 2017
Media Release Basel, 21 July 2017 CHMP recommends EU approval for Roche s TECENTRIQ (atezolizumab) in a specific type of metastatic lung and two types of metastatic bladder cancer TECENTRIQ as a potential
More informationEffective Implementation of Bayesian Adaptive Randomization in Early Phase Clinical Development. Pantelis Vlachos.
Effective Implementation of Bayesian Adaptive Randomization in Early Phase Clinical Development Pantelis Vlachos Cytel Inc, Geneva Acknowledgement Joint work with Giacomo Mordenti, Grünenthal Virginie
More informationPower & Sample Size. Dr. Andrea Benedetti
Power & Sample Size Dr. Andrea Benedetti Plan Review of hypothesis testing Power and sample size Basic concepts Formulae for common study designs Using the software When should you think about power &
More informationKaspar Rufibach (F. Hoffmann-La Roche) Joint work with Mouna Akacha (Novartis)
Treatment effect measures for time-to-event endpoints - Estimands and beyond Kaspar Rufibach (F. Hoffmann-La Roche) Joint work with Mouna Akacha (Novartis) Frankfurt, June 13 th, 2017 Problem statement
More informationDISCLOSURE SLIDE. ARGOS: research funding, scientific advisory board
INTERIM ANALYSIS OF THE PHASE 3 ADAPT TRIAL EVALUATING ROCAPULDENCEL-T (AGS-003), AN INDIVIDUALIZED IMMUNOTHERAPY FOR THE TREATMENT OF NEWLY-DIAGNOSED PATIENTS WITH METASTATIC RENAL CELL CARCINOMA (MRCC)
More informationPhase II Cancer Trials: When and How
Phase II Cancer Trials: When and How Course for New Investigators August 9-12, 2011 Learning Objectives At the end of the session the participant should be able to Define the objectives of screening vs.
More informationMedia Release. Basel, 6 th February 2018
Media Release Basel, 6 th February 2018 Phase III IMmotion151 study showed Roche's TECENTRIQ (atezolizumab) and Avastin (bevacizumab) reduced the risk of disease worsening or death by 26 percent in certain
More informationSample Size Reestimation in Non-Inferiority Trials. Heidelberg, Germany
Sample Size Reestimation in Non-Inferiority Trials Tim Friede 1 and Meinhard Kieser 2 1 Warwick Medical School, The University of Warwick, UK 2 Institute of Medical Biometry and Informatics, University
More informationRoche presents updated results for investigational cancer immunotherapy atezolizumab in advanced bladder cancer
Media Release Basel, 8 January 2016 Roche presents updated results for investigational cancer immunotherapy atezolizumab in advanced bladder cancer Higher expression of PD-L1 (programmed death-ligand 1)
More informationPhase II Cancer Trials: When and How
Phase II Cancer Trials: When and How Course for New Investigators August 21-23, 2013 Acknowledgment Elizabeth Eisenhauer for some slides! Learning Objectives At the end of the session the participant should
More informationPer the study design and a limitation of this analysis, swabs were not tested for HPV types 6
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 SUPPLEMENTARY MATERIAL Progression, regression, and clearance of HPV6/11 infections Per the study design and a limitation of this analysis, swabs
More informationDesign Concept for a Confirmatory Basket Trial
Design Concept for a Confirmatory Basket Trial Robert A. Beckman, MD 1 and Cong Chen, PhD 2 1 Professor of Oncology & of Biostatistics, Bioinformatics, and Biomathematics Lombardi Comprehensive Cancer
More informationMultiplicity Considerations in Confirmatory Subgroup Analyses
Multiplicity Considerations in Confirmatory Subgroup Analyses Frank Bretz European Statistical Meeting on Subgroup Analyses Brussels, November 30, 2012 Subgroup analyses Exploratory subgroup analyses are
More informationIntegrating Effectiveness and Safety Outcomes in the Assessment of Treatments
Integrating Effectiveness and Safety Outcomes in the Assessment of Treatments Jessica M. Franklin Instructor in Medicine Division of Pharmacoepidemiology & Pharmacoeconomics Brigham and Women s Hospital
More informationStudy Design and Analysis in Late-Stage Cancer Immunotherapy Trials
Study Design and Analysis in Late-Stage Cancer Immunotherapy Trials EMA-CDDF Joint Meeting, London, UK Tai-Tsang Chen, PhD Executive Director Global Biometrics Sciences Bristol-Myers Squibb Disclosure
More informationUsing Statistical Principles to Implement FDA Guidance on Cardiovascular Risk Assessment for Diabetes Drugs
Using Statistical Principles to Implement FDA Guidance on Cardiovascular Risk Assessment for Diabetes Drugs David Manner, Brenda Crowe and Linda Shurzinske BASS XVI November 9-13, 2009 Acknowledgements
More informationEuropean Commission approves Roche s Alecensa (alectinib) as first-line treatment in ALK-positive lung cancer
Media Release Basel, 21 December 2017 European Commission approves Roche s Alecensa (alectinib) as first-line treatment in ALK-positive lung cancer Alecensa provides a new treatment option for people with
More informationMedia Release. Basel, 20 March 2018
Media Release Basel, 20 March 2018 Phase III IMpower131 study showed Roche s TECENTRIQ (atezolizumab) plus chemotherapy (carboplatin and Abraxane) reduced the risk of disease worsening or death in the
More informationHeart rate lowering treatment in chronic heart failure
Heart rate lowering treatment in chronic heart failure Jaromir Hradec 3rd Dept. Med., Charles Univ., Prague Czech Republic Things we knew, things we did Things we have learnt, things we should do What
More informationRANDOMISED PHASE III STUDY OF ERLOTINIB VERSUS OBSERVATION IN PATIENTS WITH NO EVIDENCE OF DISEASE PROGRESSION AFTER FIRST LINE, PLATINUM-BASED
RANDOMISED PHASE III STUDY OF ERLOTINIB VERSUS OBSERVATION IN PATIENTS WITH NO EVIDENCE OF DISEASE PROGRESSION AFTER FIRST LINE, PLATINUM-BASED CHEMOTHERAPY FOR HIGH- RISK STAGE I AND STAGE II-IV OVARIAN
More informationBiost 524: Design of Medical Studies
Biost 524: Design of Medical Studies Lecture 7: Statistical Analysis Plan Susanne May, Ph.D. / Scott S. Emerson, M.D., Ph.D. Associate Professor / Professor of Biostatistics University of Washington Lecture
More informationSCHOOL OF MATHEMATICS AND STATISTICS
Data provided: Tables of distributions MAS603 SCHOOL OF MATHEMATICS AND STATISTICS Further Clinical Trials Spring Semester 014 015 hours Candidates may bring to the examination a calculator which conforms
More informationMedia Release. FDA grants Roche s Perjeta accelerated approval for use before surgery in people with HER2-positive early stage breast cancer
Media Release Basel, 1 October 2013 FDA grants Roche s Perjeta accelerated approval for use before surgery in people with HER2-positive early stage breast cancer The Perjeta regimen is the first treatment
More informationSynopsis. Study Phase and Title: Study Objectives: Overall Study Design
Synopsis Study Phase and Title: Study Objectives: Overall Study Design Phase III randomized sequential open-label study to evaluate the efficacy and safety of sorafenib followed by pazopanib versus pazopanib
More informationChoosing between different hormonal therapies. Rudy Van den Broecke UZ Ghent
Choosing between different hormonal therapies Rudy Van den Broecke UZ Ghent What is the golden standard in premenopausal hormonal sensitive early breast cancer? Ovarian Suppression alone 5 years Tamoxifen
More informationStatistical Challenges for Novel Technologies. Roseann M. White, MA Director of Pragmatic Clinical Trial Statistics Duke Clinical Research Institute
Statistical Challenges for Novel Technologies Roseann M. White, MA Director of Pragmatic Clinical Trial Statistics Duke Clinical Research Institute ISCTM 2016 Autumn Conference, Philadelphia, PA 27 September
More informationOverview of Standard Phase II Design Issues
Overview of Standard Phase II Design Issues Elizabeth Garrett-Mayer, PhD Associate Professor Hollings Cancer Center Medical University of South Carolina Primary Phase II Goals Phase II study aka Safety
More informationMedia Release. FDA grants Priority Review for Roche s Perjeta (pertuzumab) for adjuvant treatment of HER2-positive early breast cancer
Media Release Basel, 29 September 2017 FDA grants Priority Review for Roche s Perjeta (pertuzumab) for adjuvant treatment of HER2-positive early breast cancer Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced
More informationBayes-Verfahren in klinischen Studien
Bayes-Verfahren in klinischen Studien Dr. rer. nat. Joachim Gerß, Dipl.-Stat. joachim.gerss@ukmuenster.de Institute of Biostatistics and Clinical Research J. Gerß: Bayesian Methods in Clinical Trials 2
More informationJoint Modelling of Event Counts and Survival Times: Example Using Data from the MESS Trial
Joint Modelling of Event Counts and Survival Times: Example Using Data from the MESS Trial J. K. Rogers J. L. Hutton K. Hemming Department of Statistics University of Warwick Research Students Conference,
More informationRoche provides update on phase III study of TECENTRIQ (atezolizumab) in people with previously treated advanced bladder cancer
Media Release Basel, 10 May 2017 Roche provides update on phase III study of TECENTRIQ (atezolizumab) in people with previously treated advanced bladder cancer IMvigor211 study did not meet its primary
More informationCarcinosarcoma Trial rial in s a in rare malign rare mali ancy
Carcinosarcoma Trials in a rare malignancy BACKGROUND Rare and highly aggressive epithelial malignancies Biphasic tumors with epithelial and mesenchymal components Uterine carcinomas (UCS) uncommon with
More informationComparison of Futility Monitoring Methods Using RTOG Clinical Trials. Q. Ed Zhang, PhD
Comparison of Futility Monitoring Methods Using RTOG Clinical Trials Q. Ed Zhang, PhD 1 Futility Monitoring Definition: Monitoring for early determination that trial results will not be in favor of H 1
More informationClinical trial design issues and options for the study of rare diseases
Clinical trial design issues and options for the study of rare diseases November 19, 2018 Jeffrey Krischer, PhD Rare Diseases Clinical Research Network Rare Diseases Clinical Research Network (RDCRN) is
More informationConfirmatory subgroup analysis: Multiple testing approaches. Alex Dmitrienko Center for Statistics in Drug Development, Quintiles
Confirmatory subgroup analysis: Multiple testing approaches Alex Dmitrienko Center for Statistics in Drug Development, Quintiles JSM 2013 Outline Clinical trials with tailoring objectives Clinical trials
More informationAdjusting the Crossover Effect in Overall Survival Analysis Using a Rank Preserving Structural Failure Time Model: The Case of Sunitinib GIST Trial
Adjusting the Crossover Effect in Overall Survival Analysis Using a Rank Preserving Structural Failure Time Model: The Case of Sunitinib GIST Trial Xin Huang 1 and Qiang (Casey) Xu 2 1 Pfizer Oncology
More informationPackage seqdesign. April 27, Version 1.1 Date
Version 1.1 Date 2015-04-23 Package seqdesign April 27, 2015 Title Simulation and Group Sequential Monitoring of Randomized Two-Stage Treatment Efficacy Trials with Time-to-Event Endpoints Author Michal
More informationTargeted Agents as Maintenance Therapy. Karen Kelly, MD Professor of Medicine UC Davis Cancer Center
Targeted Agents as Maintenance Therapy Karen Kelly, MD Professor of Medicine UC Davis Cancer Center Disclosures Genentech Advisory Board Maintenance Therapy Defined Treatment Non-Progressing Patients Drug
More informationClinical and statistical considerations of bridging approaches to alternative dosing regimen or formulations
Clinical and statistical considerations of bridging approaches to alternative dosing regimen or formulations Dominik Heinzmann, PhD Global Development Team Leader Biostatistics Manager F. Hoffmann-La Roche,
More informationTRIALs of CDK4/6 inhibitor in women with hormone-receptor-positive metastatic breast cancer
TRIALs of CDK4/6 inhibitor in women with hormone-receptor-positive metastatic breast cancer Marta Bonotto Department of Oncology University Hospital of Udine TRIALs of CDK4/6 inhibitor in women with hormone-receptor-positive
More informationNoninferiority Clinical Trials
Noninferiority Clinical Trials Scott Evans Harvard University Brasilia, Brazil May 7, 2010 Special Obrigado Valdair Pinto, M.D. Interfarma Outline Rationale and Examples Design Assumptions Constancy Assay
More informationCost-effectiveness of ixazomib (Ninlaro ) for the Treatment of Adult Patients with Multiple Myeloma who have Received at Least One Prior Therapy
Cost-effectiveness of ixazomib (Ninlaro ) for the Treatment of Adult Patients with Multiple Myeloma who have Received at Least One Prior Therapy The NCPE has issued a recommendation regarding the cost-effectiveness
More informationContinuous Safety Monitoring of Excess Toxicity in Single Arm Early Phase Biomarker Driven Trials
Oregon Health & Science University OHSU Digital Commons Scholar Archive 4-2016 Continuous Safety Monitoring of Excess Toxicity in Single Arm Early Phase Biomarker Driven Trials Racky Daffe Follow this
More informationFDA approves Roche s Alecensa (alectinib) as first-line treatment for people with specific type of lung cancer
Media Release Basel, 07 November 2017 FDA approves Roche s Alecensa (alectinib) as first-line treatment for people with specific type of lung cancer Approval based on phase III results that showed Alecensa
More informationAccelerated approval of Perjeta for neoadjuvant use also converted to full approval
Media Release Basel, 21 December 2017 FDA approves Roche s Perjeta (pertuzumab) for adjuvant treatment of specific type of early breast cancer Accelerated approval of Perjeta for neoadjuvant use also converted
More informationThis clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data.
abcd Clinical Study for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis which is part of the clinical
More informationPTAC meeting held on 5 & 6 May (minutes for web publishing)
PTAC meeting held on 5 & 6 May 2016 (minutes for web publishing) PTAC minutes are published in accordance with the Terms of Reference for the Pharmacology and Therapeutics Advisory Committee (PTAC) and
More informationTrial design in the presence of non-exchangeable subpopulations
Trial design in the presence of non-exchangeable subpopulations Brian P. Hobbs, PhD Cancer Biostatistics Section Head in The Taussig Cancer Institute Associate Staff, Department of Quantitative Health
More informationImmunotherapy in the Adjuvant Setting for Melanoma: What You Need to Know
Immunotherapy in the Adjuvant Setting for Melanoma: What You Need to Know Jeffrey Weber, MD, PhD Laura and Isaac Perlmutter Cancer Center NYU Langone Medical Center New York, New York What Is the Current
More informationBayesian Response-Adaptive Designs for Basket Trials. Dana-Farber Cancer Institute, Boston, Massachusetts 2
Biometrics DOI: 0./biom. 0 0 0 0 Bayesian Response-Adaptive Designs for Basket Trials Steffen Ventz,,,* William T. Barry,, Giovanni Parmigiani,, and Lorenzo Trippa, Q Dana-Farber Cancer Institute, Boston,
More informationeluting Stents The SPIRIT Trials
Everolimus-eluting eluting Stents The SPIRIT Trials Gregg W. Stone, MD Columbia University Medical Center Cardiovascular Research Foundation Abbott XIENCE V Everolimus-eluting eluting Stent Everolimus
More informationIII Sessione I risultati clinici
10,30-13,15 III Sessione I risultati clinici Moderatori: Michele Maio - Valter Torri 10,30-10,45 Melanoma: anti CTLA-4 Vanna Chiarion Sileni Vanna Chiarion Sileni IOV-IRCCS,Padova Vanna.chiarion@ioveneto.it
More informationThe Role of Pathologic Complete Response (pcr) as a Surrogate Marker for Outcomes in Breast Cancer: Where Are We Now?
1 The Role of Pathologic Complete Response (pcr) as a Surrogate Marker for Outcomes in Breast Cancer: Where Are We Now? Terry Mamounas, M.D., M.P.H., F.A.C.S. Medical Director, Comprehensive Breast Program
More information1. Whether the risks of stent thrombosis (ST) and major adverse cardiovascular and cerebrovascular events (MACCE) differ from BMS and DES
1 Comparison of Ischemic and Bleeding Events After Drug- Eluting Stents or Bare Metal Stents in Subjects Receiving Dual Antiplatelet Therapy: Results from the Randomized Dual Antiplatelet Therapy (DAPT)
More informationCancer Biomarkers: Hope, Hype or Help. Does the past predict the future?
Cancer Biomarkers: Hope, Hype or Help. Does the past predict the future? ECMC Quality Assurance & Translational Science Network Group 10th Anniversary Symposium of the ECMC QATS Network Group London, May
More informationExperiences with interim trial monitoring, particularly with early stopped trials
Experiences with interim trial monitoring, particularly with early stopped trials 1 Robert J Glynn, ScD Divisions of Preventive Medicine and Pharmacoepidemiology & Pharmacoeconomics, Brigham & Women s
More informationBayesian Latent Subgroup Design for Basket Trials
Bayesian Latent Subgroup Design for Basket Trials Yiyi Chu Department of Biostatistics The University of Texas School of Public Health July 30, 2017 Outline Introduction Bayesian latent subgroup (BLAST)
More informationIs there a Cookbook for Oncology Clinical Trials?
Masterclass for Masters See beyond : An Oncology Brainstorm Ghent, 16th of September 2016 Is there a Cookbook for Oncology Clinical Trials? Dimitrios Zardavas MD Associate Scientific Director, Breast International
More informationEvolution of Early Phase Trials: Clinical Trial Design in the Modern Era
Evolution of Early Phase Trials: Clinical Trial Design in the Modern Era Shivaani Kummar, MD, FACP Professor of Medicine (Oncology) Director, Phase I Clinical Research Program Co-Director, Translational
More informationBasket Trials: Features, Examples, and Challenges
: Features, s, and Challenges Lindsay A. Renfro, Ph.D. Associate Professor of Research Division of Biostatistics University of Southern California ASA Biopharm / Regulatory / Industry Statistics Workshop
More informationThe update of the multiplicity guideline
The update of the multiplicity guideline Norbert Benda and Medical Devices (BfArM), Bonn Disclaimer: Views expressed in this presentation are the author's personal views and not necessarily the views of
More informationThe HERA Study Team. Presented by Ian E. Smith
Trastuzumab Following Adjuvant Chemotherapy in HER2-Positive Early Breast Cancer (HERA Trial): Disease-Free and Overall Survival after 2 Year Median Follow-Up The HERA Study Team Presented by Ian E. Smith
More information