SlideShare a Scribd company logo
1 of 16
1
Adaptive Clinical Trial Designs:
Health Canada’s Regulatory
Perspective
Celia Lourenco, PhD
Bureau of Gastroenterology, Infection
And Viral Diseases
Health Canada - HPFB
• Reviews and authorises clinical trial applications for
pharmaceuticals, biologics, radiopharmaceuticals,
medical devices, and natural health products
• Reviews and authorises for sale pharmaceuticals,
biologics, radiopharmaceuticals, medical devices, and
natural health products
• Carries out pharmacovigilance in clinical trials and post-
market
2
3
Main regulatory concerns
• Design should be appropriate to answer the scientific
question of interest
• Sponsor must demonstrate control of Power and Type I
error rate over the entire clinical trial
• Operational bias – appropriate pre-planning and
measures are implemented to avoid operational bias
(e.g., randomization, blinding, secure electronic
systems, independent DSMBs, blinded steering
committees, etc.)
4
Adaptive Designs
• On Health Canada’s radar for several years (HC working
group formed in 2008)
• Many seen in clinical trial applications (CTAs)
• Some in new drug submissions (NDSs)
5
HC WG definition of
adaptive design
• An adaptive clinical trial design is a study design
planned prospectively that uses accumulating
data to decide how to modify aspects of an
ongoing study and that uses pre-specified,
validated, methodological approaches to
preserve the validity and integrity of the trial
Some examples in CTAs
• Adaptive randomization, drop or add arms
– Mainly in phase 2 trials
– Use of modeling and simulation
• Sample size re-estimation: phase 2 or 3
• Seamless design: phase 2/3, two-stage dose
selection
6
7
8
Some examples in NDSs
• Indacaterol: for treatment of COPD - Trial B2335S, a
26-week seamless adaptive design trial that included
an initial 2 week dose-ranging phase
• Gardasil 9: a vaccine indicated for the prevention of
infection caused by the Human Papillomavirus (HPV)
types 6, 11, 16, 18, 31, 33, 45, 52 and 58
– A Randomized, International, Double-Blinded (With In-
House Blinding), Controlled With GARDASIL™, Dose-
Ranging, Tolerability, Immunogenicity, and Efficacy Study of
a Multivalent Human Papillomavirus (HPV) L1 Virus-Like
Particle (VLP) Vaccine Administered to 16- to 26-Year-Old
Women
9
10
B2335s Trial Design
Gardasil 9 design
• From FDA’s review on FDA’s website:
– Phase 2b/3, with two parts
– Part A: ~1240 subjects were enrolled, equally randomized to
3 dose formulations of 9vHPV or qHPV
– Part B: one dose formulation of 9vHPV was selected for Part
B based on interim immunogenicity results, with ~13,380
subjects enrolled in Part B and equally randomized to the
selected dose formulation of 9vHPV or qHPV
11
Conclusion from case-studies
• Adaptive designs present increased complexity
• May be difficult to interpret, and make use of new
statistical tests/procedures
• Increase in use of Bayesian statistics, which involves a
different approach in statistical inference
• Increase use of simulation – time consuming to
validate and can be difficult to interpret what the results
mean
12
13
• Simulation provides the operating characteristics of the
trial design
• That is the description (a picture) of the likelihood
(probabilities) of how the trial will progress down the
different paths (planned possible adaptations) to
eventual completion or termination of the trial
Why and What of Simulation
14
• The sponsors should provide that picture
• Usually in well designed and planned trials, yes
• The question is should regulators look behind the picture
and actually check that it was done right?
– That means try to duplicate the simulation results
– Ask to submit codes, and check/replicate
Seeing that Picture
Conclusions & recommendations
• Continue to monitor adaptive designs, expect that the
topic will continue to evolve
• Pre-submission meetings are encouraged
• Optimize biostatistics and IT resources to deal with
emerging trends such as use of Bayesian statistics
• Provide support and encourage attendance of courses
and seminars on adaptive design
• Biostatistics consult sought (early) for pivotal Adaptive
Design trials in submissions
15
THANK YOU!

More Related Content

What's hot

Quality assessment in systematic literature review
Quality assessment in systematic literature reviewQuality assessment in systematic literature review
Quality assessment in systematic literature reviewJingjing Lin
 
Incorporating systematic reviews into other systematic reviews: Can we save t...
Incorporating systematic reviews into other systematic reviews: Can we save t...Incorporating systematic reviews into other systematic reviews: Can we save t...
Incorporating systematic reviews into other systematic reviews: Can we save t...Cochrane.Collaboration
 
Buu Tu resume
Buu Tu resume Buu Tu resume
Buu Tu resume Buu Tu
 
Dragalin Flexible Design
Dragalin Flexible DesignDragalin Flexible Design
Dragalin Flexible Designheominkyu
 
EBM Systematic Review Appraisal Template V1
EBM Systematic Review Appraisal Template V1EBM Systematic Review Appraisal Template V1
EBM Systematic Review Appraisal Template V1Imad Hassan
 
How to conduct a systematic review
How to conduct a systematic reviewHow to conduct a systematic review
How to conduct a systematic reviewDrNidhiPruthiShukla
 
Meta Analysis of Medical Device Data Applications for Designing Studies and R...
Meta Analysis of Medical Device Data Applications for Designing Studies and R...Meta Analysis of Medical Device Data Applications for Designing Studies and R...
Meta Analysis of Medical Device Data Applications for Designing Studies and R...NAMSA
 
Quiz lec 1& 2
Quiz lec 1& 2Quiz lec 1& 2
Quiz lec 1& 2Mpdodz
 
Buu tu resume
Buu tu resumeBuu tu resume
Buu tu resumeBuu Tu
 
Clahrc ps cmeeting_21st_sept2015_spacer_project_cc
Clahrc ps cmeeting_21st_sept2015_spacer_project_ccClahrc ps cmeeting_21st_sept2015_spacer_project_cc
Clahrc ps cmeeting_21st_sept2015_spacer_project_ccNIHR CLAHRC West Midlands
 

What's hot (18)

Quality assessment in systematic literature review
Quality assessment in systematic literature reviewQuality assessment in systematic literature review
Quality assessment in systematic literature review
 
Scott Harris
Scott HarrisScott Harris
Scott Harris
 
Incorporating systematic reviews into other systematic reviews: Can we save t...
Incorporating systematic reviews into other systematic reviews: Can we save t...Incorporating systematic reviews into other systematic reviews: Can we save t...
Incorporating systematic reviews into other systematic reviews: Can we save t...
 
Buu Tu resume
Buu Tu resume Buu Tu resume
Buu Tu resume
 
Dragalin Flexible Design
Dragalin Flexible DesignDragalin Flexible Design
Dragalin Flexible Design
 
Quantitative Synthesis I
Quantitative Synthesis IQuantitative Synthesis I
Quantitative Synthesis I
 
When to Select Observational Studies Quiz
When to Select Observational Studies QuizWhen to Select Observational Studies Quiz
When to Select Observational Studies Quiz
 
EBM Systematic Review Appraisal Template V1
EBM Systematic Review Appraisal Template V1EBM Systematic Review Appraisal Template V1
EBM Systematic Review Appraisal Template V1
 
Grading Strength of Evidence
Grading Strength of EvidenceGrading Strength of Evidence
Grading Strength of Evidence
 
How to conduct a systematic review
How to conduct a systematic reviewHow to conduct a systematic review
How to conduct a systematic review
 
Topic Refinement Quiz
Topic Refinement QuizTopic Refinement Quiz
Topic Refinement Quiz
 
Data Extraction Quiz
Data  Extraction QuizData  Extraction Quiz
Data Extraction Quiz
 
Meta Analysis of Medical Device Data Applications for Designing Studies and R...
Meta Analysis of Medical Device Data Applications for Designing Studies and R...Meta Analysis of Medical Device Data Applications for Designing Studies and R...
Meta Analysis of Medical Device Data Applications for Designing Studies and R...
 
Quiz lec 1& 2
Quiz lec 1& 2Quiz lec 1& 2
Quiz lec 1& 2
 
Assessing Quality of Individual Studies Quiz
Assessing Quality of Individual Studies QuizAssessing Quality of Individual Studies Quiz
Assessing Quality of Individual Studies Quiz
 
Multivariatetechniques01
Multivariatetechniques01Multivariatetechniques01
Multivariatetechniques01
 
Buu tu resume
Buu tu resumeBuu tu resume
Buu tu resume
 
Clahrc ps cmeeting_21st_sept2015_spacer_project_cc
Clahrc ps cmeeting_21st_sept2015_spacer_project_ccClahrc ps cmeeting_21st_sept2015_spacer_project_cc
Clahrc ps cmeeting_21st_sept2015_spacer_project_cc
 

Viewers also liked (13)

Comparison of stability testing requirements of ich with other
Comparison of stability testing requirements of ich with otherComparison of stability testing requirements of ich with other
Comparison of stability testing requirements of ich with other
 
ICH Stability testing of new drug substances and products QA (R2) - 2015
ICH Stability testing of new drug substances and products QA (R2) - 2015ICH Stability testing of new drug substances and products QA (R2) - 2015
ICH Stability testing of new drug substances and products QA (R2) - 2015
 
Preparing an IND Application: CMC
Preparing an IND Application: CMCPreparing an IND Application: CMC
Preparing an IND Application: CMC
 
CGMP for IND phase I products
CGMP  for IND phase I productsCGMP  for IND phase I products
CGMP for IND phase I products
 
Quality by Design : Control strategy
Quality by Design : Control strategyQuality by Design : Control strategy
Quality by Design : Control strategy
 
Ich guidelines seminar
Ich guidelines seminarIch guidelines seminar
Ich guidelines seminar
 
Regulatory agencies
Regulatory agenciesRegulatory agencies
Regulatory agencies
 
ICH
ICHICH
ICH
 
Ich guidelines
Ich guidelinesIch guidelines
Ich guidelines
 
USFDA NDA Vs BLA
USFDA NDA Vs BLAUSFDA NDA Vs BLA
USFDA NDA Vs BLA
 
So you think you know GCP ...
So you think you know GCP ...So you think you know GCP ...
So you think you know GCP ...
 
ICH GCP
ICH GCPICH GCP
ICH GCP
 
ICH GCP
ICH GCPICH GCP
ICH GCP
 

Similar to Cadth 2015 e4 lourenco adaptive design april 2015 final

Complex Innovative Trial Designs
Complex Innovative Trial DesignsComplex Innovative Trial Designs
Complex Innovative Trial DesignsFrancois MAIGNEN
 
Adaptive Clinical Trials: Enhancing Precision and Efficiency
Adaptive Clinical Trials: Enhancing Precision and EfficiencyAdaptive Clinical Trials: Enhancing Precision and Efficiency
Adaptive Clinical Trials: Enhancing Precision and EfficiencyClinosolIndia
 
Adaptive Study Designs
Adaptive Study DesignsAdaptive Study Designs
Adaptive Study DesignsAnirudha Potey
 
Advances in Clinical Trial Design: Adaptive and Platform Trials
Advances in Clinical Trial Design: Adaptive and Platform TrialsAdvances in Clinical Trial Design: Adaptive and Platform Trials
Advances in Clinical Trial Design: Adaptive and Platform TrialsClinosolIndia
 
Advances in Clincal Trial Design- Adaptive and Platform Trials
Advances in Clincal Trial Design- Adaptive and Platform TrialsAdvances in Clincal Trial Design- Adaptive and Platform Trials
Advances in Clincal Trial Design- Adaptive and Platform TrialsClinosolIndia
 
Current Trends in Clinical Trial Design and Execution
Current Trends in Clinical Trial Design and Execution Current Trends in Clinical Trial Design and Execution
Current Trends in Clinical Trial Design and Execution ClinosolIndia
 
trial and protocol design
trial and protocol design trial and protocol design
trial and protocol design Rohit K.
 
Protocol Design & Development: What You Need to Know to Ensure a Successful S...
Protocol Design & Development: What You Need to Know to Ensure a Successful S...Protocol Design & Development: What You Need to Know to Ensure a Successful S...
Protocol Design & Development: What You Need to Know to Ensure a Successful S...Brook White, PMP
 
Role of Biostatistics in Clinical Trials
Role of Biostatistics in Clinical TrialsRole of Biostatistics in Clinical Trials
Role of Biostatistics in Clinical TrialsClinosolIndia
 
The Blueprint for Success for Effective and Efficient Clinical Protocols.pptx
The Blueprint for Success for Effective and Efficient Clinical Protocols.pptxThe Blueprint for Success for Effective and Efficient Clinical Protocols.pptx
The Blueprint for Success for Effective and Efficient Clinical Protocols.pptxMMS Holdings
 
Aug2015 zivana tezak analytical validation
Aug2015 zivana tezak analytical validationAug2015 zivana tezak analytical validation
Aug2015 zivana tezak analytical validationGenomeInABottle
 
Strategy to incorporate pharmacoeconomics into pharmacotherapy
Strategy to incorporate pharmacoeconomics into pharmacotherapy Strategy to incorporate pharmacoeconomics into pharmacotherapy
Strategy to incorporate pharmacoeconomics into pharmacotherapy Ravi Kumar Yadav
 
Study Design in Bioequivalence Studies.pptx
Study Design in Bioequivalence Studies.pptxStudy Design in Bioequivalence Studies.pptx
Study Design in Bioequivalence Studies.pptxGauravPatil763872
 
dkNET Webinar: Choosing Sample Sizes for Multilevel and Longitudinal Studies ...
dkNET Webinar: Choosing Sample Sizes for Multilevel and Longitudinal Studies ...dkNET Webinar: Choosing Sample Sizes for Multilevel and Longitudinal Studies ...
dkNET Webinar: Choosing Sample Sizes for Multilevel and Longitudinal Studies ...dkNET
 
Operational research
Operational researchOperational research
Operational researchjyotinayak44
 
Final navigating multiple clinical trial requirements for the us
Final navigating multiple clinical trial requirements for the usFinal navigating multiple clinical trial requirements for the us
Final navigating multiple clinical trial requirements for the usBhaswat Chakraborty
 
Redefining the Gold Standard
Redefining the Gold StandardRedefining the Gold Standard
Redefining the Gold StandardCovance
 
resume-stael-dumesle - SD - update
resume-stael-dumesle - SD - updateresume-stael-dumesle - SD - update
resume-stael-dumesle - SD - updateStael Dumesle
 

Similar to Cadth 2015 e4 lourenco adaptive design april 2015 final (20)

Complex Innovative Trial Designs
Complex Innovative Trial DesignsComplex Innovative Trial Designs
Complex Innovative Trial Designs
 
Adaptive Clinical Trials: Enhancing Precision and Efficiency
Adaptive Clinical Trials: Enhancing Precision and EfficiencyAdaptive Clinical Trials: Enhancing Precision and Efficiency
Adaptive Clinical Trials: Enhancing Precision and Efficiency
 
Adaptive Study Designs
Adaptive Study DesignsAdaptive Study Designs
Adaptive Study Designs
 
Advances in Clinical Trial Design: Adaptive and Platform Trials
Advances in Clinical Trial Design: Adaptive and Platform TrialsAdvances in Clinical Trial Design: Adaptive and Platform Trials
Advances in Clinical Trial Design: Adaptive and Platform Trials
 
Advances in Clincal Trial Design- Adaptive and Platform Trials
Advances in Clincal Trial Design- Adaptive and Platform TrialsAdvances in Clincal Trial Design- Adaptive and Platform Trials
Advances in Clincal Trial Design- Adaptive and Platform Trials
 
Current Trends in Clinical Trial Design and Execution
Current Trends in Clinical Trial Design and Execution Current Trends in Clinical Trial Design and Execution
Current Trends in Clinical Trial Design and Execution
 
trial and protocol design
trial and protocol design trial and protocol design
trial and protocol design
 
Protocol Design & Development: What You Need to Know to Ensure a Successful S...
Protocol Design & Development: What You Need to Know to Ensure a Successful S...Protocol Design & Development: What You Need to Know to Ensure a Successful S...
Protocol Design & Development: What You Need to Know to Ensure a Successful S...
 
Role of Biostatistics in Clinical Trials
Role of Biostatistics in Clinical TrialsRole of Biostatistics in Clinical Trials
Role of Biostatistics in Clinical Trials
 
The Blueprint for Success for Effective and Efficient Clinical Protocols.pptx
The Blueprint for Success for Effective and Efficient Clinical Protocols.pptxThe Blueprint for Success for Effective and Efficient Clinical Protocols.pptx
The Blueprint for Success for Effective and Efficient Clinical Protocols.pptx
 
Aug2015 zivana tezak analytical validation
Aug2015 zivana tezak analytical validationAug2015 zivana tezak analytical validation
Aug2015 zivana tezak analytical validation
 
Strategy to incorporate pharmacoeconomics into pharmacotherapy
Strategy to incorporate pharmacoeconomics into pharmacotherapy Strategy to incorporate pharmacoeconomics into pharmacotherapy
Strategy to incorporate pharmacoeconomics into pharmacotherapy
 
Study Design in Bioequivalence Studies.pptx
Study Design in Bioequivalence Studies.pptxStudy Design in Bioequivalence Studies.pptx
Study Design in Bioequivalence Studies.pptx
 
dkNET Webinar: Choosing Sample Sizes for Multilevel and Longitudinal Studies ...
dkNET Webinar: Choosing Sample Sizes for Multilevel and Longitudinal Studies ...dkNET Webinar: Choosing Sample Sizes for Multilevel and Longitudinal Studies ...
dkNET Webinar: Choosing Sample Sizes for Multilevel and Longitudinal Studies ...
 
Operational research
Operational researchOperational research
Operational research
 
Clinical trial design
Clinical trial designClinical trial design
Clinical trial design
 
Final navigating multiple clinical trial requirements for the us
Final navigating multiple clinical trial requirements for the usFinal navigating multiple clinical trial requirements for the us
Final navigating multiple clinical trial requirements for the us
 
4 Dr Jian Wang Health Canada
4 Dr Jian Wang   Health Canada4 Dr Jian Wang   Health Canada
4 Dr Jian Wang Health Canada
 
Redefining the Gold Standard
Redefining the Gold StandardRedefining the Gold Standard
Redefining the Gold Standard
 
resume-stael-dumesle - SD - update
resume-stael-dumesle - SD - updateresume-stael-dumesle - SD - update
resume-stael-dumesle - SD - update
 

More from CADTH Symposium

Cadth symp breakfast 4 Update to Guidelines for the Economic Evaluation of He...
Cadth symp breakfast 4 Update to Guidelines for the Economic Evaluation of He...Cadth symp breakfast 4 Update to Guidelines for the Economic Evaluation of He...
Cadth symp breakfast 4 Update to Guidelines for the Economic Evaluation of He...CADTH Symposium
 
Cadth 2015 e1 deal prader willi cadth
Cadth 2015 e1 deal prader willi cadthCadth 2015 e1 deal prader willi cadth
Cadth 2015 e1 deal prader willi cadthCADTH Symposium
 
Cadth 2015 e2 dd systemic review-ohtac aug13-2013_2
Cadth 2015 e2 dd systemic review-ohtac aug13-2013_2Cadth 2015 e2 dd systemic review-ohtac aug13-2013_2
Cadth 2015 e2 dd systemic review-ohtac aug13-2013_2CADTH Symposium
 
Cadth 2015 e6 husereau rwe cadth
Cadth 2015 e6 husereau rwe cadthCadth 2015 e6 husereau rwe cadth
Cadth 2015 e6 husereau rwe cadthCADTH Symposium
 
Cadth 2015 e4 fields slides for adaptive panel final
Cadth 2015 e4 fields slides for adaptive panel finalCadth 2015 e4 fields slides for adaptive panel final
Cadth 2015 e4 fields slides for adaptive panel finalCADTH Symposium
 
Cadth 2015 e4 mcelwee cadth 041415 fnl
Cadth 2015 e4 mcelwee cadth 041415 fnlCadth 2015 e4 mcelwee cadth 041415 fnl
Cadth 2015 e4 mcelwee cadth 041415 fnlCADTH Symposium
 
Cadth 2015 e4 thorlund innovative trial designs in medical decision making
Cadth 2015 e4 thorlund innovative trial designs in medical decision makingCadth 2015 e4 thorlund innovative trial designs in medical decision making
Cadth 2015 e4 thorlund innovative trial designs in medical decision makingCADTH Symposium
 
Cadth 2015 e1 2015 04 cadth v2.0
Cadth 2015 e1 2015 04 cadth v2.0Cadth 2015 e1 2015 04 cadth v2.0
Cadth 2015 e1 2015 04 cadth v2.0CADTH Symposium
 
Cadth 2015 e4 adaptive design april 2015 final lourenco
Cadth 2015 e4 adaptive design april 2015 final lourencoCadth 2015 e4 adaptive design april 2015 final lourenco
Cadth 2015 e4 adaptive design april 2015 final lourencoCADTH Symposium
 
Cadth symposium 2015 d3 pr os va. generic measures cadth 14th april 2015
Cadth symposium 2015 d3 pr os va. generic measures cadth 14th april 2015Cadth symposium 2015 d3 pr os va. generic measures cadth 14th april 2015
Cadth symposium 2015 d3 pr os va. generic measures cadth 14th april 2015CADTH Symposium
 
Cadth 2015 d5 symposium 2015 endonodal trials - version 2
Cadth 2015 d5 symposium 2015   endonodal trials - version 2Cadth 2015 d5 symposium 2015   endonodal trials - version 2
Cadth 2015 d5 symposium 2015 endonodal trials - version 2CADTH Symposium
 
Cadth 2015 e5 ad panel discussion af
Cadth 2015 e5 ad panel discussion   afCadth 2015 e5 ad panel discussion   af
Cadth 2015 e5 ad panel discussion afCADTH Symposium
 
Cadth 2015 e5 noac ad symposium_panel_14apr2015
Cadth 2015 e5 noac ad symposium_panel_14apr2015Cadth 2015 e5 noac ad symposium_panel_14apr2015
Cadth 2015 e5 noac ad symposium_panel_14apr2015CADTH Symposium
 
Cadth 2015 b1 slides allan grill-pcodr-cadth_symposium2015presentationfinal
Cadth 2015 b1 slides allan grill-pcodr-cadth_symposium2015presentationfinalCadth 2015 b1 slides allan grill-pcodr-cadth_symposium2015presentationfinal
Cadth 2015 b1 slides allan grill-pcodr-cadth_symposium2015presentationfinalCADTH Symposium
 
Cadth 2015 breakfast 2 excel hta tools presentation final
Cadth 2015 breakfast 2 excel hta tools presentation   finalCadth 2015 breakfast 2 excel hta tools presentation   final
Cadth 2015 breakfast 2 excel hta tools presentation finalCADTH Symposium
 
Cadth 2015 d7 burgess cadth 2015 20150414
Cadth 2015 d7 burgess cadth 2015 20150414Cadth 2015 d7 burgess cadth 2015 20150414
Cadth 2015 d7 burgess cadth 2015 20150414CADTH Symposium
 
Cadth 2015 d7 presentation 2015 14 apr15
Cadth 2015 d7 presentation 2015 14 apr15Cadth 2015 d7 presentation 2015 14 apr15
Cadth 2015 d7 presentation 2015 14 apr15CADTH Symposium
 
Cadth 2015 d4 lidia engel final
Cadth 2015 d4 lidia engel finalCadth 2015 d4 lidia engel final
Cadth 2015 d4 lidia engel finalCADTH Symposium
 
Cadth 2015 d2 procurement oral presentation-vf
Cadth 2015 d2 procurement oral presentation-vfCadth 2015 d2 procurement oral presentation-vf
Cadth 2015 d2 procurement oral presentation-vfCADTH Symposium
 

More from CADTH Symposium (20)

Cadth symp breakfast 4 Update to Guidelines for the Economic Evaluation of He...
Cadth symp breakfast 4 Update to Guidelines for the Economic Evaluation of He...Cadth symp breakfast 4 Update to Guidelines for the Economic Evaluation of He...
Cadth symp breakfast 4 Update to Guidelines for the Economic Evaluation of He...
 
Cadth 2015 e1 deal prader willi cadth
Cadth 2015 e1 deal prader willi cadthCadth 2015 e1 deal prader willi cadth
Cadth 2015 e1 deal prader willi cadth
 
Cadth 2015 e2 dd systemic review-ohtac aug13-2013_2
Cadth 2015 e2 dd systemic review-ohtac aug13-2013_2Cadth 2015 e2 dd systemic review-ohtac aug13-2013_2
Cadth 2015 e2 dd systemic review-ohtac aug13-2013_2
 
Cadth 2015 e3 eq5 d
Cadth 2015 e3  eq5 dCadth 2015 e3  eq5 d
Cadth 2015 e3 eq5 d
 
Cadth 2015 e6 husereau rwe cadth
Cadth 2015 e6 husereau rwe cadthCadth 2015 e6 husereau rwe cadth
Cadth 2015 e6 husereau rwe cadth
 
Cadth 2015 e4 fields slides for adaptive panel final
Cadth 2015 e4 fields slides for adaptive panel finalCadth 2015 e4 fields slides for adaptive panel final
Cadth 2015 e4 fields slides for adaptive panel final
 
Cadth 2015 e4 mcelwee cadth 041415 fnl
Cadth 2015 e4 mcelwee cadth 041415 fnlCadth 2015 e4 mcelwee cadth 041415 fnl
Cadth 2015 e4 mcelwee cadth 041415 fnl
 
Cadth 2015 e4 thorlund innovative trial designs in medical decision making
Cadth 2015 e4 thorlund innovative trial designs in medical decision makingCadth 2015 e4 thorlund innovative trial designs in medical decision making
Cadth 2015 e4 thorlund innovative trial designs in medical decision making
 
Cadth 2015 e1 2015 04 cadth v2.0
Cadth 2015 e1 2015 04 cadth v2.0Cadth 2015 e1 2015 04 cadth v2.0
Cadth 2015 e1 2015 04 cadth v2.0
 
Cadth 2015 e4 adaptive design april 2015 final lourenco
Cadth 2015 e4 adaptive design april 2015 final lourencoCadth 2015 e4 adaptive design april 2015 final lourenco
Cadth 2015 e4 adaptive design april 2015 final lourenco
 
Cadth symposium 2015 d3 pr os va. generic measures cadth 14th april 2015
Cadth symposium 2015 d3 pr os va. generic measures cadth 14th april 2015Cadth symposium 2015 d3 pr os va. generic measures cadth 14th april 2015
Cadth symposium 2015 d3 pr os va. generic measures cadth 14th april 2015
 
Cadth 2015 d5 symposium 2015 endonodal trials - version 2
Cadth 2015 d5 symposium 2015   endonodal trials - version 2Cadth 2015 d5 symposium 2015   endonodal trials - version 2
Cadth 2015 d5 symposium 2015 endonodal trials - version 2
 
Cadth 2015 e5 ad panel discussion af
Cadth 2015 e5 ad panel discussion   afCadth 2015 e5 ad panel discussion   af
Cadth 2015 e5 ad panel discussion af
 
Cadth 2015 e5 noac ad symposium_panel_14apr2015
Cadth 2015 e5 noac ad symposium_panel_14apr2015Cadth 2015 e5 noac ad symposium_panel_14apr2015
Cadth 2015 e5 noac ad symposium_panel_14apr2015
 
Cadth 2015 b1 slides allan grill-pcodr-cadth_symposium2015presentationfinal
Cadth 2015 b1 slides allan grill-pcodr-cadth_symposium2015presentationfinalCadth 2015 b1 slides allan grill-pcodr-cadth_symposium2015presentationfinal
Cadth 2015 b1 slides allan grill-pcodr-cadth_symposium2015presentationfinal
 
Cadth 2015 breakfast 2 excel hta tools presentation final
Cadth 2015 breakfast 2 excel hta tools presentation   finalCadth 2015 breakfast 2 excel hta tools presentation   final
Cadth 2015 breakfast 2 excel hta tools presentation final
 
Cadth 2015 d7 burgess cadth 2015 20150414
Cadth 2015 d7 burgess cadth 2015 20150414Cadth 2015 d7 burgess cadth 2015 20150414
Cadth 2015 d7 burgess cadth 2015 20150414
 
Cadth 2015 d7 presentation 2015 14 apr15
Cadth 2015 d7 presentation 2015 14 apr15Cadth 2015 d7 presentation 2015 14 apr15
Cadth 2015 d7 presentation 2015 14 apr15
 
Cadth 2015 d4 lidia engel final
Cadth 2015 d4 lidia engel finalCadth 2015 d4 lidia engel final
Cadth 2015 d4 lidia engel final
 
Cadth 2015 d2 procurement oral presentation-vf
Cadth 2015 d2 procurement oral presentation-vfCadth 2015 d2 procurement oral presentation-vf
Cadth 2015 d2 procurement oral presentation-vf
 

Recently uploaded

Call Girls Faridabad Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Faridabad Just Call 9907093804 Top Class Call Girl Service AvailableCall Girls Faridabad Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Faridabad Just Call 9907093804 Top Class Call Girl Service AvailableDipal Arora
 
All Time Service Available Call Girls Marine Drive 📳 9820252231 For 18+ VIP C...
All Time Service Available Call Girls Marine Drive 📳 9820252231 For 18+ VIP C...All Time Service Available Call Girls Marine Drive 📳 9820252231 For 18+ VIP C...
All Time Service Available Call Girls Marine Drive 📳 9820252231 For 18+ VIP C...Arohi Goyal
 
Call Girls Nagpur Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Nagpur Just Call 9907093804 Top Class Call Girl Service AvailableCall Girls Nagpur Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Nagpur Just Call 9907093804 Top Class Call Girl Service AvailableDipal Arora
 
Top Rated Bangalore Call Girls Mg Road ⟟ 9332606886 ⟟ Call Me For Genuine S...
Top Rated Bangalore Call Girls Mg Road ⟟   9332606886 ⟟ Call Me For Genuine S...Top Rated Bangalore Call Girls Mg Road ⟟   9332606886 ⟟ Call Me For Genuine S...
Top Rated Bangalore Call Girls Mg Road ⟟ 9332606886 ⟟ Call Me For Genuine S...narwatsonia7
 
Call Girls Bangalore Just Call 8250077686 Top Class Call Girl Service Available
Call Girls Bangalore Just Call 8250077686 Top Class Call Girl Service AvailableCall Girls Bangalore Just Call 8250077686 Top Class Call Girl Service Available
Call Girls Bangalore Just Call 8250077686 Top Class Call Girl Service AvailableDipal Arora
 
Premium Call Girls In Jaipur {8445551418} ❤️VVIP SEEMA Call Girl in Jaipur Ra...
Premium Call Girls In Jaipur {8445551418} ❤️VVIP SEEMA Call Girl in Jaipur Ra...Premium Call Girls In Jaipur {8445551418} ❤️VVIP SEEMA Call Girl in Jaipur Ra...
Premium Call Girls In Jaipur {8445551418} ❤️VVIP SEEMA Call Girl in Jaipur Ra...parulsinha
 
Night 7k to 12k Chennai City Center Call Girls 👉👉 7427069034⭐⭐ 100% Genuine E...
Night 7k to 12k Chennai City Center Call Girls 👉👉 7427069034⭐⭐ 100% Genuine E...Night 7k to 12k Chennai City Center Call Girls 👉👉 7427069034⭐⭐ 100% Genuine E...
Night 7k to 12k Chennai City Center Call Girls 👉👉 7427069034⭐⭐ 100% Genuine E...hotbabesbook
 
(👑VVIP ISHAAN ) Russian Call Girls Service Navi Mumbai🖕9920874524🖕Independent...
(👑VVIP ISHAAN ) Russian Call Girls Service Navi Mumbai🖕9920874524🖕Independent...(👑VVIP ISHAAN ) Russian Call Girls Service Navi Mumbai🖕9920874524🖕Independent...
(👑VVIP ISHAAN ) Russian Call Girls Service Navi Mumbai🖕9920874524🖕Independent...Taniya Sharma
 
O898O367676 Call Girls In Ahmedabad Escort Service Available 24×7 In Ahmedabad
O898O367676 Call Girls In Ahmedabad Escort Service Available 24×7 In AhmedabadO898O367676 Call Girls In Ahmedabad Escort Service Available 24×7 In Ahmedabad
O898O367676 Call Girls In Ahmedabad Escort Service Available 24×7 In AhmedabadGENUINE ESCORT AGENCY
 
Call Girls Visakhapatnam Just Call 8250077686 Top Class Call Girl Service Ava...
Call Girls Visakhapatnam Just Call 8250077686 Top Class Call Girl Service Ava...Call Girls Visakhapatnam Just Call 8250077686 Top Class Call Girl Service Ava...
Call Girls Visakhapatnam Just Call 8250077686 Top Class Call Girl Service Ava...Dipal Arora
 
Premium Call Girls Cottonpet Whatsapp 7001035870 Independent Escort Service
Premium Call Girls Cottonpet Whatsapp 7001035870 Independent Escort ServicePremium Call Girls Cottonpet Whatsapp 7001035870 Independent Escort Service
Premium Call Girls Cottonpet Whatsapp 7001035870 Independent Escort Servicevidya singh
 
Call Girls Kochi Just Call 8250077686 Top Class Call Girl Service Available
Call Girls Kochi Just Call 8250077686 Top Class Call Girl Service AvailableCall Girls Kochi Just Call 8250077686 Top Class Call Girl Service Available
Call Girls Kochi Just Call 8250077686 Top Class Call Girl Service AvailableDipal Arora
 
Call Girls Dehradun Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Dehradun Just Call 9907093804 Top Class Call Girl Service AvailableCall Girls Dehradun Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Dehradun Just Call 9907093804 Top Class Call Girl Service AvailableDipal Arora
 
VIP Service Call Girls Sindhi Colony 📳 7877925207 For 18+ VIP Call Girl At Th...
VIP Service Call Girls Sindhi Colony 📳 7877925207 For 18+ VIP Call Girl At Th...VIP Service Call Girls Sindhi Colony 📳 7877925207 For 18+ VIP Call Girl At Th...
VIP Service Call Girls Sindhi Colony 📳 7877925207 For 18+ VIP Call Girl At Th...jageshsingh5554
 
Call Girls Coimbatore Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Coimbatore Just Call 9907093804 Top Class Call Girl Service AvailableCall Girls Coimbatore Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Coimbatore Just Call 9907093804 Top Class Call Girl Service AvailableDipal Arora
 
Best Rate (Patna ) Call Girls Patna ⟟ 8617370543 ⟟ High Class Call Girl In 5 ...
Best Rate (Patna ) Call Girls Patna ⟟ 8617370543 ⟟ High Class Call Girl In 5 ...Best Rate (Patna ) Call Girls Patna ⟟ 8617370543 ⟟ High Class Call Girl In 5 ...
Best Rate (Patna ) Call Girls Patna ⟟ 8617370543 ⟟ High Class Call Girl In 5 ...Dipal Arora
 
Call Girls Gwalior Just Call 8617370543 Top Class Call Girl Service Available
Call Girls Gwalior Just Call 8617370543 Top Class Call Girl Service AvailableCall Girls Gwalior Just Call 8617370543 Top Class Call Girl Service Available
Call Girls Gwalior Just Call 8617370543 Top Class Call Girl Service AvailableDipal Arora
 
VIP Hyderabad Call Girls Bahadurpally 7877925207 ₹5000 To 25K With AC Room 💚😋
VIP Hyderabad Call Girls Bahadurpally 7877925207 ₹5000 To 25K With AC Room 💚😋VIP Hyderabad Call Girls Bahadurpally 7877925207 ₹5000 To 25K With AC Room 💚😋
VIP Hyderabad Call Girls Bahadurpally 7877925207 ₹5000 To 25K With AC Room 💚😋TANUJA PANDEY
 
Call Girls Haridwar Just Call 8250077686 Top Class Call Girl Service Available
Call Girls Haridwar Just Call 8250077686 Top Class Call Girl Service AvailableCall Girls Haridwar Just Call 8250077686 Top Class Call Girl Service Available
Call Girls Haridwar Just Call 8250077686 Top Class Call Girl Service AvailableDipal Arora
 

Recently uploaded (20)

Call Girls Faridabad Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Faridabad Just Call 9907093804 Top Class Call Girl Service AvailableCall Girls Faridabad Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Faridabad Just Call 9907093804 Top Class Call Girl Service Available
 
All Time Service Available Call Girls Marine Drive 📳 9820252231 For 18+ VIP C...
All Time Service Available Call Girls Marine Drive 📳 9820252231 For 18+ VIP C...All Time Service Available Call Girls Marine Drive 📳 9820252231 For 18+ VIP C...
All Time Service Available Call Girls Marine Drive 📳 9820252231 For 18+ VIP C...
 
Call Girls Nagpur Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Nagpur Just Call 9907093804 Top Class Call Girl Service AvailableCall Girls Nagpur Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Nagpur Just Call 9907093804 Top Class Call Girl Service Available
 
Top Rated Bangalore Call Girls Mg Road ⟟ 9332606886 ⟟ Call Me For Genuine S...
Top Rated Bangalore Call Girls Mg Road ⟟   9332606886 ⟟ Call Me For Genuine S...Top Rated Bangalore Call Girls Mg Road ⟟   9332606886 ⟟ Call Me For Genuine S...
Top Rated Bangalore Call Girls Mg Road ⟟ 9332606886 ⟟ Call Me For Genuine S...
 
Call Girls Bangalore Just Call 8250077686 Top Class Call Girl Service Available
Call Girls Bangalore Just Call 8250077686 Top Class Call Girl Service AvailableCall Girls Bangalore Just Call 8250077686 Top Class Call Girl Service Available
Call Girls Bangalore Just Call 8250077686 Top Class Call Girl Service Available
 
Premium Call Girls In Jaipur {8445551418} ❤️VVIP SEEMA Call Girl in Jaipur Ra...
Premium Call Girls In Jaipur {8445551418} ❤️VVIP SEEMA Call Girl in Jaipur Ra...Premium Call Girls In Jaipur {8445551418} ❤️VVIP SEEMA Call Girl in Jaipur Ra...
Premium Call Girls In Jaipur {8445551418} ❤️VVIP SEEMA Call Girl in Jaipur Ra...
 
Night 7k to 12k Chennai City Center Call Girls 👉👉 7427069034⭐⭐ 100% Genuine E...
Night 7k to 12k Chennai City Center Call Girls 👉👉 7427069034⭐⭐ 100% Genuine E...Night 7k to 12k Chennai City Center Call Girls 👉👉 7427069034⭐⭐ 100% Genuine E...
Night 7k to 12k Chennai City Center Call Girls 👉👉 7427069034⭐⭐ 100% Genuine E...
 
(👑VVIP ISHAAN ) Russian Call Girls Service Navi Mumbai🖕9920874524🖕Independent...
(👑VVIP ISHAAN ) Russian Call Girls Service Navi Mumbai🖕9920874524🖕Independent...(👑VVIP ISHAAN ) Russian Call Girls Service Navi Mumbai🖕9920874524🖕Independent...
(👑VVIP ISHAAN ) Russian Call Girls Service Navi Mumbai🖕9920874524🖕Independent...
 
Call Girls in Gagan Vihar (delhi) call me [🔝 9953056974 🔝] escort service 24X7
Call Girls in Gagan Vihar (delhi) call me [🔝  9953056974 🔝] escort service 24X7Call Girls in Gagan Vihar (delhi) call me [🔝  9953056974 🔝] escort service 24X7
Call Girls in Gagan Vihar (delhi) call me [🔝 9953056974 🔝] escort service 24X7
 
O898O367676 Call Girls In Ahmedabad Escort Service Available 24×7 In Ahmedabad
O898O367676 Call Girls In Ahmedabad Escort Service Available 24×7 In AhmedabadO898O367676 Call Girls In Ahmedabad Escort Service Available 24×7 In Ahmedabad
O898O367676 Call Girls In Ahmedabad Escort Service Available 24×7 In Ahmedabad
 
Call Girls Visakhapatnam Just Call 8250077686 Top Class Call Girl Service Ava...
Call Girls Visakhapatnam Just Call 8250077686 Top Class Call Girl Service Ava...Call Girls Visakhapatnam Just Call 8250077686 Top Class Call Girl Service Ava...
Call Girls Visakhapatnam Just Call 8250077686 Top Class Call Girl Service Ava...
 
Premium Call Girls Cottonpet Whatsapp 7001035870 Independent Escort Service
Premium Call Girls Cottonpet Whatsapp 7001035870 Independent Escort ServicePremium Call Girls Cottonpet Whatsapp 7001035870 Independent Escort Service
Premium Call Girls Cottonpet Whatsapp 7001035870 Independent Escort Service
 
Call Girls Kochi Just Call 8250077686 Top Class Call Girl Service Available
Call Girls Kochi Just Call 8250077686 Top Class Call Girl Service AvailableCall Girls Kochi Just Call 8250077686 Top Class Call Girl Service Available
Call Girls Kochi Just Call 8250077686 Top Class Call Girl Service Available
 
Call Girls Dehradun Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Dehradun Just Call 9907093804 Top Class Call Girl Service AvailableCall Girls Dehradun Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Dehradun Just Call 9907093804 Top Class Call Girl Service Available
 
VIP Service Call Girls Sindhi Colony 📳 7877925207 For 18+ VIP Call Girl At Th...
VIP Service Call Girls Sindhi Colony 📳 7877925207 For 18+ VIP Call Girl At Th...VIP Service Call Girls Sindhi Colony 📳 7877925207 For 18+ VIP Call Girl At Th...
VIP Service Call Girls Sindhi Colony 📳 7877925207 For 18+ VIP Call Girl At Th...
 
Call Girls Coimbatore Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Coimbatore Just Call 9907093804 Top Class Call Girl Service AvailableCall Girls Coimbatore Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Coimbatore Just Call 9907093804 Top Class Call Girl Service Available
 
Best Rate (Patna ) Call Girls Patna ⟟ 8617370543 ⟟ High Class Call Girl In 5 ...
Best Rate (Patna ) Call Girls Patna ⟟ 8617370543 ⟟ High Class Call Girl In 5 ...Best Rate (Patna ) Call Girls Patna ⟟ 8617370543 ⟟ High Class Call Girl In 5 ...
Best Rate (Patna ) Call Girls Patna ⟟ 8617370543 ⟟ High Class Call Girl In 5 ...
 
Call Girls Gwalior Just Call 8617370543 Top Class Call Girl Service Available
Call Girls Gwalior Just Call 8617370543 Top Class Call Girl Service AvailableCall Girls Gwalior Just Call 8617370543 Top Class Call Girl Service Available
Call Girls Gwalior Just Call 8617370543 Top Class Call Girl Service Available
 
VIP Hyderabad Call Girls Bahadurpally 7877925207 ₹5000 To 25K With AC Room 💚😋
VIP Hyderabad Call Girls Bahadurpally 7877925207 ₹5000 To 25K With AC Room 💚😋VIP Hyderabad Call Girls Bahadurpally 7877925207 ₹5000 To 25K With AC Room 💚😋
VIP Hyderabad Call Girls Bahadurpally 7877925207 ₹5000 To 25K With AC Room 💚😋
 
Call Girls Haridwar Just Call 8250077686 Top Class Call Girl Service Available
Call Girls Haridwar Just Call 8250077686 Top Class Call Girl Service AvailableCall Girls Haridwar Just Call 8250077686 Top Class Call Girl Service Available
Call Girls Haridwar Just Call 8250077686 Top Class Call Girl Service Available
 

Cadth 2015 e4 lourenco adaptive design april 2015 final

  • 1. 1 Adaptive Clinical Trial Designs: Health Canada’s Regulatory Perspective Celia Lourenco, PhD Bureau of Gastroenterology, Infection And Viral Diseases
  • 2. Health Canada - HPFB • Reviews and authorises clinical trial applications for pharmaceuticals, biologics, radiopharmaceuticals, medical devices, and natural health products • Reviews and authorises for sale pharmaceuticals, biologics, radiopharmaceuticals, medical devices, and natural health products • Carries out pharmacovigilance in clinical trials and post- market 2
  • 3. 3 Main regulatory concerns • Design should be appropriate to answer the scientific question of interest • Sponsor must demonstrate control of Power and Type I error rate over the entire clinical trial • Operational bias – appropriate pre-planning and measures are implemented to avoid operational bias (e.g., randomization, blinding, secure electronic systems, independent DSMBs, blinded steering committees, etc.)
  • 4. 4 Adaptive Designs • On Health Canada’s radar for several years (HC working group formed in 2008) • Many seen in clinical trial applications (CTAs) • Some in new drug submissions (NDSs)
  • 5. 5 HC WG definition of adaptive design • An adaptive clinical trial design is a study design planned prospectively that uses accumulating data to decide how to modify aspects of an ongoing study and that uses pre-specified, validated, methodological approaches to preserve the validity and integrity of the trial
  • 6. Some examples in CTAs • Adaptive randomization, drop or add arms – Mainly in phase 2 trials – Use of modeling and simulation • Sample size re-estimation: phase 2 or 3 • Seamless design: phase 2/3, two-stage dose selection 6
  • 7. 7
  • 8. 8
  • 9. Some examples in NDSs • Indacaterol: for treatment of COPD - Trial B2335S, a 26-week seamless adaptive design trial that included an initial 2 week dose-ranging phase • Gardasil 9: a vaccine indicated for the prevention of infection caused by the Human Papillomavirus (HPV) types 6, 11, 16, 18, 31, 33, 45, 52 and 58 – A Randomized, International, Double-Blinded (With In- House Blinding), Controlled With GARDASIL™, Dose- Ranging, Tolerability, Immunogenicity, and Efficacy Study of a Multivalent Human Papillomavirus (HPV) L1 Virus-Like Particle (VLP) Vaccine Administered to 16- to 26-Year-Old Women 9
  • 11. Gardasil 9 design • From FDA’s review on FDA’s website: – Phase 2b/3, with two parts – Part A: ~1240 subjects were enrolled, equally randomized to 3 dose formulations of 9vHPV or qHPV – Part B: one dose formulation of 9vHPV was selected for Part B based on interim immunogenicity results, with ~13,380 subjects enrolled in Part B and equally randomized to the selected dose formulation of 9vHPV or qHPV 11
  • 12. Conclusion from case-studies • Adaptive designs present increased complexity • May be difficult to interpret, and make use of new statistical tests/procedures • Increase in use of Bayesian statistics, which involves a different approach in statistical inference • Increase use of simulation – time consuming to validate and can be difficult to interpret what the results mean 12
  • 13. 13 • Simulation provides the operating characteristics of the trial design • That is the description (a picture) of the likelihood (probabilities) of how the trial will progress down the different paths (planned possible adaptations) to eventual completion or termination of the trial Why and What of Simulation
  • 14. 14 • The sponsors should provide that picture • Usually in well designed and planned trials, yes • The question is should regulators look behind the picture and actually check that it was done right? – That means try to duplicate the simulation results – Ask to submit codes, and check/replicate Seeing that Picture
  • 15. Conclusions & recommendations • Continue to monitor adaptive designs, expect that the topic will continue to evolve • Pre-submission meetings are encouraged • Optimize biostatistics and IT resources to deal with emerging trends such as use of Bayesian statistics • Provide support and encourage attendance of courses and seminars on adaptive design • Biostatistics consult sought (early) for pivotal Adaptive Design trials in submissions 15