SlideShare a Scribd company logo
Clinical Proof-of-Concept (POC)
Ashwin Gollerkeri, M.D.
OutlineOutline
 Exploratory Drug Development
 Defining POC Defining POC
 Improving Probability of Success with Greater
Emphasis on POCp
 Improving POC Through Better Patient Selection
 Practical Considerations of Patient Selection
Strategies
 Summary/conclusion
Exploratory Drug Development- Phase I/IIExploratory Drug Development Phase I/II
P li i l
Phase I
(Fi t i
Phase II
(P f f Ph III R i t tiPre-clinical (First-in-
Human)
(Proof-of-
Concept)
Phase III Registration
• Evaluate safety/PK
E l i f
• Establish POC
Inform phase 3
Phase 1 Phase II
S f t Effi (
• Inform phase 2
• Early signs of
efficacy
• Inform phase 2
• Inform phase 3
Endpoints
• Safety
• PK
• Efficacy (response
rates, time-to-event)
Outcomes
• Dose/regimen for
Phase 2 and beyond
• Efficacy sufficient for
Phase 3/ registration
Design • Dose-escalation
• Single-arm
• Randomized
Patient
population
• Unrestricted
• Restricted to
indication
Sample size • 30-50 • 75-150
Success Rates from First-in-Man to
RegistrationRegistration
Kola & Landis (2004) Nature Rev Drug Disc
Success Rates by Phase of DevelopmentSuccess Rates by Phase of Development
Kola & Landis (2004) Nature Rev Drug Disc
Cost of Drug Development by PhaseCost of Drug Development by Phase
Roy A (2012) Manhattan Institute
Defining POCDefining POC
 PhRMA recommendation:
“POC is the earliest point in drug development processPOC is the earliest point in drug development process
at which the weight of evidence suggests that it is
“reasonably likely” that the key attributes for success
are present and the key causes of failure absent”
 Varies by person, project, candidate, etc…
Goals by end of PoCGoals by end of PoC
P li i l
Phase I
(Fi t i
Phase II
(P f f Ph III R i t tiPre-clinical (First-in-
Human)
(Proof-of-
Concept)
Phase III Registration
• Establish POC
Inform phase 3
We’d like to know
• Inform phase 3
We d like to know
 Best dose and regimen (safety driven)
 Indications
 Administered in combination with what, if anything
 Patients who will respond
Pfizer Confidential │ 8
 Degree of efficacy
POC Essential ElementsPOC Essential Elements
 Define essential elements of target product profile
 Determine level of risk tolerance for POC Determine level of risk tolerance for POC
 Low weight of evidence when consequences of being
wrong are benign and benefits of speed are high
 High weight of evidence where consequences of wrong High weight of evidence where consequences of wrong
POC are severe
 Determine which elements of POC are already
“reasonably likely” on basis of prior information
 Determine which of the remaining elements are not
likely to be significant threats to the programlikely to be significant threats to the program
 Determine which of the still remaining elements
cannot be practically evaluated or changed
Decision Criteria for POCDecision Criteria for POC
 Based on outcome
 Set required effect size (∆) lower reference value Set required effect size (∆), lower reference value
(LRV) below which, drug would not have value
HR TV HR MAV
HR ≤ 0.63 &
0.63 0.80 1.00
PFS
Hazard ratio
HR ≤ 0.63 &
Upper bound of 90% CI < 1 &
Upper bound of 50% CI ≤ 0.80
GO to phase III NO GO
HR≥ 0.80
Re‐evaluate
1-sided
significance
level of 0.10
and 80%
power
GO to phase III NO GO
Examples of Oncology POC TrialsExamples of Oncology POC Trials
 Design
 Randomized in same patient population as phase
III/registration
 Standard-of-care (SOC) +/- Experimental compound
 Experimental compound vs. SOC
 Single- arm trial
 Compare with historical controls
 Endpointsp
 Same as endpoints which will be used in phase III/Registration
 Time-to-event (OS, PFS)
 PFS typically favored due to shorter trial; need to correlate withyp y ;
registrational endpoint (usually OS)
 Sample sizes
 Typically based on 1-sided α 0.05, 80% poweryp y , p
 75‐80 patients per arm of randomized study
Attrition of Last-Stage Drug DevelopmentAttrition of Last Stage Drug Development
Adapted from Arrowsmith 2011
Patient Selection Strategies to Reduce
Attrition in Phase 3Attrition in Phase 3
 Advantages to using biomarker to identify
patients likely to benefitpatients likely to benefit
 Smaller sample sizes required
 More expeditious path to reach Go/No Go to phase 3
 Less expensive
 Avoids treating patients with little opportunity of benefitting
 Success of biomarker selection dependent on: Success of biomarker selection dependent on:
 Prevalence of marker
 Effect size
 Clinical performance of diagnostic assay
Patient Selection StrategiesPatient Selection Strategies
 Prospectively select biomarker positive patients
 Requires confidence that biomarker is predictive of Requires confidence that biomarker is predictive of
outcome
 Need for clinical data in biomarker-negative patients
 Enrich for biomarker positive patients in otherwise all-
comers trial
 Retrospective analysis of response based on Retrospective analysis of response based on
biomarker
 Efficacy signal may be diluted by biomarker-negative
patients
 Adaptive designs to incorporate biomarker
information in Phase 2information in Phase 2
Patient Selection Strategies
 Incorporation of stratified medicine approach leads to increase in
eNPV versus all-comers
Patient Selection Strategies
• Increased eNPV when patient selection used
prospectively (e.g. trastuzumab)
• Negative effects of eNPV when patient
selection used retrospectively (e.g.
panitumumab)
Trusheim et. al. 2011
Evolution of Non-Small Cell Lung Cancer
TreatmentTreatment
Martin Reck , et. al., The Lancet, Volume 382, Issue 9893, 2013, 709 - 719
Reck et. al. 2013
Clinical Experience in 1st L NSCLC: All-
comers vs. patient selectioncomers vs. patient selection
Patient
Efficacy
Response Progression-free
Overall survival: mo
Population Treatment Sample Size Rate: % survival: mo
Overall survival: mo
Paclitaxel-
cisplatin
1599
23-25
(v. 12)
4.3-4.9
(v. 2.7)
9.3-10.0
(v. 7.4)
Gemcitabine- 2522
26 5.2 9.0
All-comers
cisplatin
2522
(v. 10) (v. 3.7) (v. 7.6)
Gefitinib
(EGFR-
inhibitor) +
31,093
41,037
51,059
No improvement v. chemotherapy
chemotherapy 61,172
EGFR-
mutated
Gefitinib
(EGFR-
inhibitor) v.
7261
71
(v. 47)
9.5
(v. 6.3)
21.6
(v. 21.9)
(15%
NSCLC)
chemotherapy
Erlotinib v.
chemotherapy
8174
65
(v. 16)
10.4
(v. 5.2)
22.9
(v. 19.5)
ALK- Crizotinib
65 7 7
rearranged
(5% NSCLC)
(ALK-inhibitor) 9347
65
(v. 20)
7.7
(v. 3.0)
Not available
1Taxol® package insert; 2Gemzar® package insert 3Giaccone et. al. (2004);  4Herbst et. al. (2004);  5Herbst et. al. (2005); 6Getzemeier et. al. (2007); 
7Iressa® package insert; 8Tarceva® package insert
Practical considerationsPractical considerations
 Need for sufficient patient samples
 CLIA-certified assays needed for patient selection CLIA-certified assays needed for patient selection
 Establishment of cut-offs for biomarker expression
 Prevalence of biomarker-positive population Prevalence of biomarker positive population
 Evidence for correlation between biomarker
expression and outcomep
 Seemless decision points if adaptive trial design
used
 Prevent extended slowing or stopping of enrollment
during study
Summary and ConclusionsSummary and Conclusions
 High cost of attrition in phase 3 setting is shifting
emphasis to better design of phase 2 trialsemphasis to better design of phase 2 trials
 Establishing appropriate POC in exploratory
development critical for improving probability of
success in phase 3
 Recent shift in oncology drug development toward
f ti ti t l ti i tt t tfocus on prospective patient selection in attempts to
address poor overall success rates
 Adaptive study designs being considered to Adaptive study designs being considered to
efficiently use biomarker data
 Practical considerations need to be addressed to
ensure success
ReferencesReferences
 Arrowsmith J. Phase II failures: 2008-2010. Nat Rev Drug Disc (2011);10:1
 Cartwright ME, Cohen S, Fleishaker JC, et. al. Proof of concept: a PhRMA position paper with
recommendations for best practice. Nature (2010);87;278
DiM i JA H RW G b ki HG Th i f i ti ti t f d DiMasi JA, Hansen RW, Grabowski HG. The price of innovation: new estimates of drug
development costs. J Health Econ (2003);22:151
 Gatzemeier U, Pluzanska A, Szczesna A, et. al. Phase III study of erlotinib in combination with
cisplatin and gemcitabine in advanced non-small-cell lung cancer: the Tarceva lung cancer
investigation trial. J Clin Oncol (2007);25;1545
G G S C G f Giaccone G, Herbst RS, Manegold C, et. al. Gefitinib in combination with gemcitabine and
cisplatin in advanced non-small-cell lung cancer: a phase III trial-INTACT 1. J Clin Oncol
(2004);22:777
 Herbst RS, Giaccone G, Schiller JH, et. al. Gefitinib in combination with paclitaxel and carboplatin
in advanced non-small cell lung cancer: a phase III trial- INTACT 2. J Clin Oncol (2004);22:785
 Herbst RS, Prager D, Hermann R, et. al. TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-
774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung
cancer. J Clin Oncol (2005);23:5892
 Kola I and Landis J. Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Disc
(2004);3:711
 Reck M, Heigner DF, Mak T, et. al. Management of non-small-cell lung cancer: recent
developments. Lancet (2013);382:709
 Roy SA. Stifling new cures: The true cost of lengthy clinical drug trials. Project FDA (2012).
Manhattan Institute for Policy Research. http://www.manhattan-institute.org/html/fda_05.htm
 Trusheim MR Burgess B Hu SX et al Quantifying factors for the success of stratified medicine Trusheim MR, Burgess B, Hu SX, et.al. Quantifying factors for the success of stratified medicine.
Nat Rev Drug Disc (2011);10:817

More Related Content

What's hot

Clinical Trials
Clinical TrialsClinical Trials
Clinical Trials
Menaal Kaushal
 
Good Clinical Practices
Good Clinical PracticesGood Clinical Practices
Good Clinical Practices
Karun Kumar
 
ICH GCP
ICH GCPICH GCP
Phases of clinical trial 11.9.14
Phases of clinical trial 11.9.14Phases of clinical trial 11.9.14
Phases of clinical trial 11.9.14
DR ANUP PETARE
 
Phase 0 and Phase 1 clinical trial
Phase 0 and Phase 1 clinical trialPhase 0 and Phase 1 clinical trial
Phase 0 and Phase 1 clinical trial
Dr. Yash Panchal
 
Fda med watch
Fda med watchFda med watch
Fda med watch
Sridhar S
 
New ct rule 2019
New ct rule 2019New ct rule 2019
Cinical trial protocol writing
Cinical trial protocol writingCinical trial protocol writing
Cinical trial protocol writing
Urmila Aswar
 
Drug and safety monitoring board
Drug and safety  monitoring boardDrug and safety  monitoring board
Drug and safety monitoring board
Ramakanth Gadepalli
 
Regulation Governing Clinical Trials In India,USA and Europe.
Regulation Governing Clinical Trials In India,USA and Europe.  Regulation Governing Clinical Trials In India,USA and Europe.
Regulation Governing Clinical Trials In India,USA and Europe.
KapilKumar198
 
Clinical Trials Introduction
Clinical Trials IntroductionClinical Trials Introduction
Clinical Trials Introductionbiinoida
 
Data & safety monitoring boards
Data & safety monitoring boardsData & safety monitoring boards
Data & safety monitoring boardsmadhuri miriyala
 
Clinical drug development
Clinical drug developmentClinical drug development
Clinical drug development
Prof. Dr. Basavaraj Nanjwade
 
Drug development process and clinical trial for UGs
Drug development process and clinical trial for UGsDrug development process and clinical trial for UGs
Drug development process and clinical trial for UGs
SameerKhasbage
 
Clinical trials
Clinical trialsClinical trials
Clinical trials
Siddhant Bansode
 
Clinical trials
Clinical  trialsClinical  trials
Clinical trials
Nilesh Siddhawar
 
Drug development process
Drug development processDrug development process
Drug development process
nasim arshadi
 
Phases 3,4 and 5 of clinical trials
Phases 3,4 and 5 of  clinical trialsPhases 3,4 and 5 of  clinical trials
Phases 3,4 and 5 of clinical trials
DrShrey Bhatia
 
Documentation clinical trial
Documentation clinical trialDocumentation clinical trial
Documentation clinical trial
ankit sharma
 

What's hot (20)

Clinical Trials
Clinical TrialsClinical Trials
Clinical Trials
 
Good Clinical Practices
Good Clinical PracticesGood Clinical Practices
Good Clinical Practices
 
ICH GCP
ICH GCPICH GCP
ICH GCP
 
Phases of clinical trial 11.9.14
Phases of clinical trial 11.9.14Phases of clinical trial 11.9.14
Phases of clinical trial 11.9.14
 
Preclinical trials
Preclinical trialsPreclinical trials
Preclinical trials
 
Phase 0 and Phase 1 clinical trial
Phase 0 and Phase 1 clinical trialPhase 0 and Phase 1 clinical trial
Phase 0 and Phase 1 clinical trial
 
Fda med watch
Fda med watchFda med watch
Fda med watch
 
New ct rule 2019
New ct rule 2019New ct rule 2019
New ct rule 2019
 
Cinical trial protocol writing
Cinical trial protocol writingCinical trial protocol writing
Cinical trial protocol writing
 
Drug and safety monitoring board
Drug and safety  monitoring boardDrug and safety  monitoring board
Drug and safety monitoring board
 
Regulation Governing Clinical Trials In India,USA and Europe.
Regulation Governing Clinical Trials In India,USA and Europe.  Regulation Governing Clinical Trials In India,USA and Europe.
Regulation Governing Clinical Trials In India,USA and Europe.
 
Clinical Trials Introduction
Clinical Trials IntroductionClinical Trials Introduction
Clinical Trials Introduction
 
Data & safety monitoring boards
Data & safety monitoring boardsData & safety monitoring boards
Data & safety monitoring boards
 
Clinical drug development
Clinical drug developmentClinical drug development
Clinical drug development
 
Drug development process and clinical trial for UGs
Drug development process and clinical trial for UGsDrug development process and clinical trial for UGs
Drug development process and clinical trial for UGs
 
Clinical trials
Clinical trialsClinical trials
Clinical trials
 
Clinical trials
Clinical  trialsClinical  trials
Clinical trials
 
Drug development process
Drug development processDrug development process
Drug development process
 
Phases 3,4 and 5 of clinical trials
Phases 3,4 and 5 of  clinical trialsPhases 3,4 and 5 of  clinical trials
Phases 3,4 and 5 of clinical trials
 
Documentation clinical trial
Documentation clinical trialDocumentation clinical trial
Documentation clinical trial
 

Viewers also liked

An example of a successful proof of concept
An example of a successful proof of conceptAn example of a successful proof of concept
An example of a successful proof of concept
ETLSolutions
 
Post-launch experiences from a locally developed internal proof of concept im...
Post-launch experiences from a locally developed internal proof of concept im...Post-launch experiences from a locally developed internal proof of concept im...
Post-launch experiences from a locally developed internal proof of concept im...
Sebastian Schumann
 
Proof of Concept - Prototype Agreement Jul 2011
Proof of Concept - Prototype Agreement Jul 2011Proof of Concept - Prototype Agreement Jul 2011
Proof of Concept - Prototype Agreement Jul 2011mvwickham78
 
OTN tour 2015 Oracle Enterprise Manager 12c – Proof of Concept
OTN tour 2015 Oracle Enterprise Manager 12c – Proof of ConceptOTN tour 2015 Oracle Enterprise Manager 12c – Proof of Concept
OTN tour 2015 Oracle Enterprise Manager 12c – Proof of Concept
Andrejs Vorobjovs
 
VMworld 2015: Conducting a Successful Virtual SAN Proof of Concept
VMworld 2015: Conducting a Successful Virtual SAN Proof of ConceptVMworld 2015: Conducting a Successful Virtual SAN Proof of Concept
VMworld 2015: Conducting a Successful Virtual SAN Proof of Concept
VMworld
 
Proof of Concept with Real Application Testing 12c
Proof of Concept with Real Application Testing 12cProof of Concept with Real Application Testing 12c
Proof of Concept with Real Application Testing 12c
Luis Marques
 
Optimizing Preclinical Proof of Concept
Optimizing Preclinical Proof of ConceptOptimizing Preclinical Proof of Concept
Optimizing Preclinical Proof of Concept
MaRS Discovery District
 
Twiliocon Europe 2013: From PoC to Production, Lessons Learnt, by Erol Ziya &...
Twiliocon Europe 2013: From PoC to Production, Lessons Learnt, by Erol Ziya &...Twiliocon Europe 2013: From PoC to Production, Lessons Learnt, by Erol Ziya &...
Twiliocon Europe 2013: From PoC to Production, Lessons Learnt, by Erol Ziya &...
eazynow
 
PoC: Using a Group Communication System to improve MySQL Replication HA
PoC: Using a Group Communication System to improve MySQL Replication HAPoC: Using a Group Communication System to improve MySQL Replication HA
PoC: Using a Group Communication System to improve MySQL Replication HA
Ulf Wendel
 
Case Study: Lessons from Newell Rubbermaid's SAP HANA Proof of Concept
Case Study: Lessons from Newell Rubbermaid's SAP HANA Proof of ConceptCase Study: Lessons from Newell Rubbermaid's SAP HANA Proof of Concept
Case Study: Lessons from Newell Rubbermaid's SAP HANA Proof of Concept
SAPinsider Events
 
Proof-Of-Concept
Proof-Of-ConceptProof-Of-Concept
Proof-Of-Concept
Diana Rangaves, PharmD, CEO
 
Accelerating Innovation: Proof of Concept Gap Fund Program Best Practices
Accelerating Innovation: Proof of Concept Gap Fund Program Best PracticesAccelerating Innovation: Proof of Concept Gap Fund Program Best Practices
Accelerating Innovation: Proof of Concept Gap Fund Program Best Practices
innovosource
 
IBM Predictive analytics IoT Presentation
IBM Predictive analytics IoT PresentationIBM Predictive analytics IoT Presentation
IBM Predictive analytics IoT PresentationIan Skerrett
 
Proof of Concept Workshop
Proof of Concept WorkshopProof of Concept Workshop
Proof of Concept Workshop
Danny Holtschke
 
Big Data Proof of Concept
Big Data Proof of ConceptBig Data Proof of Concept
Big Data Proof of Concept
RCG Global Services
 
How to Build a Proof of Concept
How to Build a Proof of Concept How to Build a Proof of Concept
How to Build a Proof of Concept
Michael Hamilton
 
Introduction to pre clinical screening of drugs
Introduction to pre clinical screening of drugsIntroduction to pre clinical screening of drugs
Introduction to pre clinical screening of drugs
Kanthlal SK
 

Viewers also liked (17)

An example of a successful proof of concept
An example of a successful proof of conceptAn example of a successful proof of concept
An example of a successful proof of concept
 
Post-launch experiences from a locally developed internal proof of concept im...
Post-launch experiences from a locally developed internal proof of concept im...Post-launch experiences from a locally developed internal proof of concept im...
Post-launch experiences from a locally developed internal proof of concept im...
 
Proof of Concept - Prototype Agreement Jul 2011
Proof of Concept - Prototype Agreement Jul 2011Proof of Concept - Prototype Agreement Jul 2011
Proof of Concept - Prototype Agreement Jul 2011
 
OTN tour 2015 Oracle Enterprise Manager 12c – Proof of Concept
OTN tour 2015 Oracle Enterprise Manager 12c – Proof of ConceptOTN tour 2015 Oracle Enterprise Manager 12c – Proof of Concept
OTN tour 2015 Oracle Enterprise Manager 12c – Proof of Concept
 
VMworld 2015: Conducting a Successful Virtual SAN Proof of Concept
VMworld 2015: Conducting a Successful Virtual SAN Proof of ConceptVMworld 2015: Conducting a Successful Virtual SAN Proof of Concept
VMworld 2015: Conducting a Successful Virtual SAN Proof of Concept
 
Proof of Concept with Real Application Testing 12c
Proof of Concept with Real Application Testing 12cProof of Concept with Real Application Testing 12c
Proof of Concept with Real Application Testing 12c
 
Optimizing Preclinical Proof of Concept
Optimizing Preclinical Proof of ConceptOptimizing Preclinical Proof of Concept
Optimizing Preclinical Proof of Concept
 
Twiliocon Europe 2013: From PoC to Production, Lessons Learnt, by Erol Ziya &...
Twiliocon Europe 2013: From PoC to Production, Lessons Learnt, by Erol Ziya &...Twiliocon Europe 2013: From PoC to Production, Lessons Learnt, by Erol Ziya &...
Twiliocon Europe 2013: From PoC to Production, Lessons Learnt, by Erol Ziya &...
 
PoC: Using a Group Communication System to improve MySQL Replication HA
PoC: Using a Group Communication System to improve MySQL Replication HAPoC: Using a Group Communication System to improve MySQL Replication HA
PoC: Using a Group Communication System to improve MySQL Replication HA
 
Case Study: Lessons from Newell Rubbermaid's SAP HANA Proof of Concept
Case Study: Lessons from Newell Rubbermaid's SAP HANA Proof of ConceptCase Study: Lessons from Newell Rubbermaid's SAP HANA Proof of Concept
Case Study: Lessons from Newell Rubbermaid's SAP HANA Proof of Concept
 
Proof-Of-Concept
Proof-Of-ConceptProof-Of-Concept
Proof-Of-Concept
 
Accelerating Innovation: Proof of Concept Gap Fund Program Best Practices
Accelerating Innovation: Proof of Concept Gap Fund Program Best PracticesAccelerating Innovation: Proof of Concept Gap Fund Program Best Practices
Accelerating Innovation: Proof of Concept Gap Fund Program Best Practices
 
IBM Predictive analytics IoT Presentation
IBM Predictive analytics IoT PresentationIBM Predictive analytics IoT Presentation
IBM Predictive analytics IoT Presentation
 
Proof of Concept Workshop
Proof of Concept WorkshopProof of Concept Workshop
Proof of Concept Workshop
 
Big Data Proof of Concept
Big Data Proof of ConceptBig Data Proof of Concept
Big Data Proof of Concept
 
How to Build a Proof of Concept
How to Build a Proof of Concept How to Build a Proof of Concept
How to Build a Proof of Concept
 
Introduction to pre clinical screening of drugs
Introduction to pre clinical screening of drugsIntroduction to pre clinical screening of drugs
Introduction to pre clinical screening of drugs
 

Similar to Clinical Proof of Concept (PoC)

Potential of phase II clinical trials in drug development
Potential of phase II clinical trials in drug developmentPotential of phase II clinical trials in drug development
Potential of phase II clinical trials in drug developmentBhaswat Chakraborty
 
Gene Profiling in Clinical Oncology - Slide 10 - H. Rugo - Why genomic tools ...
Gene Profiling in Clinical Oncology - Slide 10 - H. Rugo - Why genomic tools ...Gene Profiling in Clinical Oncology - Slide 10 - H. Rugo - Why genomic tools ...
Gene Profiling in Clinical Oncology - Slide 10 - H. Rugo - Why genomic tools ...European School of Oncology
 
Biomarker Discovery For Early Clin Dev Dublin Oct 2008
Biomarker Discovery For Early Clin Dev   Dublin Oct 2008Biomarker Discovery For Early Clin Dev   Dublin Oct 2008
Biomarker Discovery For Early Clin Dev Dublin Oct 2008
Mike Romanos
 
Health economic modelling in the diagnostics development process
Health economic modelling in the diagnostics development processHealth economic modelling in the diagnostics development process
Health economic modelling in the diagnostics development process
cheweb1
 
Colorectal Cancer Research & Treatment News - recap from the May 2014 ASCO co...
Colorectal Cancer Research & Treatment News - recap from the May 2014 ASCO co...Colorectal Cancer Research & Treatment News - recap from the May 2014 ASCO co...
Colorectal Cancer Research & Treatment News - recap from the May 2014 ASCO co...
Fight Colorectal Cancer
 
Jean Marc Nabholtz : Médicaments biologiques : Critères d’enregistrement et d...
Jean Marc Nabholtz : Médicaments biologiques : Critères d’enregistrement et d...Jean Marc Nabholtz : Médicaments biologiques : Critères d’enregistrement et d...
Jean Marc Nabholtz : Médicaments biologiques : Critères d’enregistrement et d...breastcancerupdatecongress
 
2015 11-26 ODDP2015 Course Oncology Drug Development, Amsterdam, Alain van Gool
2015 11-26 ODDP2015 Course Oncology Drug Development, Amsterdam, Alain van Gool2015 11-26 ODDP2015 Course Oncology Drug Development, Amsterdam, Alain van Gool
2015 11-26 ODDP2015 Course Oncology Drug Development, Amsterdam, Alain van Gool
Alain van Gool
 
Analyzing ASCO 2016: Developments, takeaways, and implications from the confe...
Analyzing ASCO 2016: Developments, takeaways, and implications from the confe...Analyzing ASCO 2016: Developments, takeaways, and implications from the confe...
Analyzing ASCO 2016: Developments, takeaways, and implications from the confe...
Pharma Intelligence
 
Antibiotic prophylaxis in sever Acute Panceriatitis
Antibiotic prophylaxis in sever Acute PanceriatitisAntibiotic prophylaxis in sever Acute Panceriatitis
Antibiotic prophylaxis in sever Acute PanceriatitisSaeed Al-Shomimi
 
Lyman_Reiner_Morrow_Crawford_annalsApril2015
Lyman_Reiner_Morrow_Crawford_annalsApril2015Lyman_Reiner_Morrow_Crawford_annalsApril2015
Lyman_Reiner_Morrow_Crawford_annalsApril2015Maureen Reiner
 
Clinical trial options for rare diseases
Clinical trial options for rare diseasesClinical trial options for rare diseases
Clinical trial options for rare diseases
Albert Farrugia
 
Improving Patient Outcomes With Cancer Immunotherapies Throughout the Lung Ca...
Improving Patient Outcomes With Cancer Immunotherapies Throughout the Lung Ca...Improving Patient Outcomes With Cancer Immunotherapies Throughout the Lung Ca...
Improving Patient Outcomes With Cancer Immunotherapies Throughout the Lung Ca...
PVI, PeerView Institute for Medical Education
 
2023 HR Positive / HER2-Negative early breast cancer consensus
2023 HR Positive / HER2-Negative early breast cancer consensus2023 HR Positive / HER2-Negative early breast cancer consensus
2023 HR Positive / HER2-Negative early breast cancer consensus
ssuserc11ccf
 
Tips-Tricks-Clinical-Trial-Endpoints.pdf
Tips-Tricks-Clinical-Trial-Endpoints.pdfTips-Tricks-Clinical-Trial-Endpoints.pdf
Tips-Tricks-Clinical-Trial-Endpoints.pdf
Nikhil Sebastian
 
NY Prostate Cancer Conference - M.H. Hussain - Session 7: Role of predictive ...
NY Prostate Cancer Conference - M.H. Hussain - Session 7: Role of predictive ...NY Prostate Cancer Conference - M.H. Hussain - Session 7: Role of predictive ...
NY Prostate Cancer Conference - M.H. Hussain - Session 7: Role of predictive ...European School of Oncology
 
Recent evidences in Breast cancer.
Recent evidences in Breast cancer.Recent evidences in Breast cancer.
Recent evidences in Breast cancer.
Dr. Abhishek Basu
 
Chemotherapy+with+or+without+gefitinib+in+patients+with+advanced+non small-ce...
Chemotherapy+with+or+without+gefitinib+in+patients+with+advanced+non small-ce...Chemotherapy+with+or+without+gefitinib+in+patients+with+advanced+non small-ce...
Chemotherapy+with+or+without+gefitinib+in+patients+with+advanced+non small-ce...Mina Max
 
Medical Students 2011 - J.B. Vermorken - INTRODUCTION TO CANCER TREATMENT - I...
Medical Students 2011 - J.B. Vermorken - INTRODUCTION TO CANCER TREATMENT - I...Medical Students 2011 - J.B. Vermorken - INTRODUCTION TO CANCER TREATMENT - I...
Medical Students 2011 - J.B. Vermorken - INTRODUCTION TO CANCER TREATMENT - I...European School of Oncology
 
Advances In Adjuvant Systemic Therapy Of Breast Cancer
Advances In Adjuvant Systemic Therapy Of Breast CancerAdvances In Adjuvant Systemic Therapy Of Breast Cancer
Advances In Adjuvant Systemic Therapy Of Breast Cancerfondas vakalis
 
Target Validation Academy Of Medical Sciences 1 Dec 2006
Target Validation   Academy Of Medical Sciences 1 Dec 2006Target Validation   Academy Of Medical Sciences 1 Dec 2006
Target Validation Academy Of Medical Sciences 1 Dec 2006
Mike Romanos
 

Similar to Clinical Proof of Concept (PoC) (20)

Potential of phase II clinical trials in drug development
Potential of phase II clinical trials in drug developmentPotential of phase II clinical trials in drug development
Potential of phase II clinical trials in drug development
 
Gene Profiling in Clinical Oncology - Slide 10 - H. Rugo - Why genomic tools ...
Gene Profiling in Clinical Oncology - Slide 10 - H. Rugo - Why genomic tools ...Gene Profiling in Clinical Oncology - Slide 10 - H. Rugo - Why genomic tools ...
Gene Profiling in Clinical Oncology - Slide 10 - H. Rugo - Why genomic tools ...
 
Biomarker Discovery For Early Clin Dev Dublin Oct 2008
Biomarker Discovery For Early Clin Dev   Dublin Oct 2008Biomarker Discovery For Early Clin Dev   Dublin Oct 2008
Biomarker Discovery For Early Clin Dev Dublin Oct 2008
 
Health economic modelling in the diagnostics development process
Health economic modelling in the diagnostics development processHealth economic modelling in the diagnostics development process
Health economic modelling in the diagnostics development process
 
Colorectal Cancer Research & Treatment News - recap from the May 2014 ASCO co...
Colorectal Cancer Research & Treatment News - recap from the May 2014 ASCO co...Colorectal Cancer Research & Treatment News - recap from the May 2014 ASCO co...
Colorectal Cancer Research & Treatment News - recap from the May 2014 ASCO co...
 
Jean Marc Nabholtz : Médicaments biologiques : Critères d’enregistrement et d...
Jean Marc Nabholtz : Médicaments biologiques : Critères d’enregistrement et d...Jean Marc Nabholtz : Médicaments biologiques : Critères d’enregistrement et d...
Jean Marc Nabholtz : Médicaments biologiques : Critères d’enregistrement et d...
 
2015 11-26 ODDP2015 Course Oncology Drug Development, Amsterdam, Alain van Gool
2015 11-26 ODDP2015 Course Oncology Drug Development, Amsterdam, Alain van Gool2015 11-26 ODDP2015 Course Oncology Drug Development, Amsterdam, Alain van Gool
2015 11-26 ODDP2015 Course Oncology Drug Development, Amsterdam, Alain van Gool
 
Analyzing ASCO 2016: Developments, takeaways, and implications from the confe...
Analyzing ASCO 2016: Developments, takeaways, and implications from the confe...Analyzing ASCO 2016: Developments, takeaways, and implications from the confe...
Analyzing ASCO 2016: Developments, takeaways, and implications from the confe...
 
Antibiotic prophylaxis in sever Acute Panceriatitis
Antibiotic prophylaxis in sever Acute PanceriatitisAntibiotic prophylaxis in sever Acute Panceriatitis
Antibiotic prophylaxis in sever Acute Panceriatitis
 
Lyman_Reiner_Morrow_Crawford_annalsApril2015
Lyman_Reiner_Morrow_Crawford_annalsApril2015Lyman_Reiner_Morrow_Crawford_annalsApril2015
Lyman_Reiner_Morrow_Crawford_annalsApril2015
 
Clinical trial options for rare diseases
Clinical trial options for rare diseasesClinical trial options for rare diseases
Clinical trial options for rare diseases
 
Improving Patient Outcomes With Cancer Immunotherapies Throughout the Lung Ca...
Improving Patient Outcomes With Cancer Immunotherapies Throughout the Lung Ca...Improving Patient Outcomes With Cancer Immunotherapies Throughout the Lung Ca...
Improving Patient Outcomes With Cancer Immunotherapies Throughout the Lung Ca...
 
2023 HR Positive / HER2-Negative early breast cancer consensus
2023 HR Positive / HER2-Negative early breast cancer consensus2023 HR Positive / HER2-Negative early breast cancer consensus
2023 HR Positive / HER2-Negative early breast cancer consensus
 
Tips-Tricks-Clinical-Trial-Endpoints.pdf
Tips-Tricks-Clinical-Trial-Endpoints.pdfTips-Tricks-Clinical-Trial-Endpoints.pdf
Tips-Tricks-Clinical-Trial-Endpoints.pdf
 
NY Prostate Cancer Conference - M.H. Hussain - Session 7: Role of predictive ...
NY Prostate Cancer Conference - M.H. Hussain - Session 7: Role of predictive ...NY Prostate Cancer Conference - M.H. Hussain - Session 7: Role of predictive ...
NY Prostate Cancer Conference - M.H. Hussain - Session 7: Role of predictive ...
 
Recent evidences in Breast cancer.
Recent evidences in Breast cancer.Recent evidences in Breast cancer.
Recent evidences in Breast cancer.
 
Chemotherapy+with+or+without+gefitinib+in+patients+with+advanced+non small-ce...
Chemotherapy+with+or+without+gefitinib+in+patients+with+advanced+non small-ce...Chemotherapy+with+or+without+gefitinib+in+patients+with+advanced+non small-ce...
Chemotherapy+with+or+without+gefitinib+in+patients+with+advanced+non small-ce...
 
Medical Students 2011 - J.B. Vermorken - INTRODUCTION TO CANCER TREATMENT - I...
Medical Students 2011 - J.B. Vermorken - INTRODUCTION TO CANCER TREATMENT - I...Medical Students 2011 - J.B. Vermorken - INTRODUCTION TO CANCER TREATMENT - I...
Medical Students 2011 - J.B. Vermorken - INTRODUCTION TO CANCER TREATMENT - I...
 
Advances In Adjuvant Systemic Therapy Of Breast Cancer
Advances In Adjuvant Systemic Therapy Of Breast CancerAdvances In Adjuvant Systemic Therapy Of Breast Cancer
Advances In Adjuvant Systemic Therapy Of Breast Cancer
 
Target Validation Academy Of Medical Sciences 1 Dec 2006
Target Validation   Academy Of Medical Sciences 1 Dec 2006Target Validation   Academy Of Medical Sciences 1 Dec 2006
Target Validation Academy Of Medical Sciences 1 Dec 2006
 

More from Cytel USA

From the clinic to the cfo adaptive trials and financial decision making
From the clinic to the cfo   adaptive trials and financial decision makingFrom the clinic to the cfo   adaptive trials and financial decision making
From the clinic to the cfo adaptive trials and financial decision makingCytel USA
 
Eugm 2012 unknown - incivex drug development process overview road to findi...
Eugm 2012   unknown - incivex drug development process overview road to findi...Eugm 2012   unknown - incivex drug development process overview road to findi...
Eugm 2012 unknown - incivex drug development process overview road to findi...Cytel USA
 
Eugm 2012 pritchett - application of adaptive sample size re-estimation in ...
Eugm 2012   pritchett - application of adaptive sample size re-estimation in ...Eugm 2012   pritchett - application of adaptive sample size re-estimation in ...
Eugm 2012 pritchett - application of adaptive sample size re-estimation in ...Cytel USA
 
Eugm 2012 oneill - perspective on the current environment for adaptive clin...
Eugm 2012   oneill - perspective on the current environment for adaptive clin...Eugm 2012   oneill - perspective on the current environment for adaptive clin...
Eugm 2012 oneill - perspective on the current environment for adaptive clin...Cytel USA
 
Eugm 2012 mehta - future plans for east - 2012 eugm
Eugm 2012   mehta - future plans for east - 2012 eugmEugm 2012   mehta - future plans for east - 2012 eugm
Eugm 2012 mehta - future plans for east - 2012 eugmCytel USA
 
Eugm 2012 jemiai - introduction to east architect
Eugm 2012   jemiai - introduction to east architectEugm 2012   jemiai - introduction to east architect
Eugm 2012 jemiai - introduction to east architectCytel USA
 
Eugm 2012 gaydos - design and analysis approaches to evaluate cardiovascula...
Eugm 2012   gaydos - design and analysis approaches to evaluate cardiovascula...Eugm 2012   gaydos - design and analysis approaches to evaluate cardiovascula...
Eugm 2012 gaydos - design and analysis approaches to evaluate cardiovascula...Cytel USA
 
Eugm 2012 demets - clinical trials and the impact of regulations
Eugm 2012   demets - clinical trials and the impact of regulationsEugm 2012   demets - clinical trials and the impact of regulations
Eugm 2012 demets - clinical trials and the impact of regulationsCytel USA
 
Eugm 2011 pocock - dm cs-and-adaptive-trials
Eugm 2011   pocock - dm cs-and-adaptive-trialsEugm 2011   pocock - dm cs-and-adaptive-trials
Eugm 2011 pocock - dm cs-and-adaptive-trialsCytel USA
 
Eugm 2011 mehta - execution of adaptive trials operational considerations
Eugm 2011   mehta - execution of adaptive trials operational considerationsEugm 2011   mehta - execution of adaptive trials operational considerations
Eugm 2011 mehta - execution of adaptive trials operational considerationsCytel USA
 
Eugm 2011 mehta - adaptive designs for phase 3 oncology trials
Eugm 2011   mehta - adaptive designs for phase 3 oncology trialsEugm 2011   mehta - adaptive designs for phase 3 oncology trials
Eugm 2011 mehta - adaptive designs for phase 3 oncology trialsCytel USA
 
EUGM 2011 | JEMIAI
EUGM 2011 | JEMIAIEUGM 2011 | JEMIAI
EUGM 2011 | JEMIAI
Cytel USA
 
EUGM 2011 | JEHL | group sequential designs with 2 time to event endpoints
EUGM 2011 | JEHL | group sequential designs with 2 time to event endpointsEUGM 2011 | JEHL | group sequential designs with 2 time to event endpoints
EUGM 2011 | JEHL | group sequential designs with 2 time to event endpoints
Cytel USA
 
EUGM 2011| Fretault | Use of bayesian approach in phase ii
EUGM 2011| Fretault | Use of bayesian approach in phase iiEUGM 2011| Fretault | Use of bayesian approach in phase ii
EUGM 2011| Fretault | Use of bayesian approach in phase ii
Cytel USA
 
EUGM 2011 | DAY | Experiences with interim analyses and dm cs
EUGM 2011 | DAY | Experiences with interim analyses and dm csEUGM 2011 | DAY | Experiences with interim analyses and dm cs
EUGM 2011 | DAY | Experiences with interim analyses and dm cs
Cytel USA
 
EUGM 2011 | DARCHY | Deployment & use of east within sanofi r & d
EUGM 2011 | DARCHY | Deployment & use of east within sanofi r & dEUGM 2011 | DARCHY | Deployment & use of east within sanofi r & d
EUGM 2011 | DARCHY | Deployment & use of east within sanofi r & d
Cytel USA
 
EUGM 2014 | BEKELE | Adaptive Dose Finding Using Toxicity Probability Intervals
EUGM 2014 | BEKELE | Adaptive Dose Finding Using Toxicity Probability IntervalsEUGM 2014 | BEKELE | Adaptive Dose Finding Using Toxicity Probability Intervals
EUGM 2014 | BEKELE | Adaptive Dose Finding Using Toxicity Probability Intervals
Cytel USA
 
EUGM 2014 | BOLOGNESE | Case Studies of Phase 2 Adaptive Dose-Finding Trials
EUGM 2014 | BOLOGNESE | Case Studies of Phase 2 Adaptive Dose-Finding TrialsEUGM 2014 | BOLOGNESE | Case Studies of Phase 2 Adaptive Dose-Finding Trials
EUGM 2014 | BOLOGNESE | Case Studies of Phase 2 Adaptive Dose-Finding Trials
Cytel USA
 
A Bayesian Industry Approach to Phase 1 Combination Trials in Oncology
A Bayesian Industry Approach to Phase 1 Combination Trials in OncologyA Bayesian Industry Approach to Phase 1 Combination Trials in Oncology
A Bayesian Industry Approach to Phase 1 Combination Trials in Oncology
Cytel USA
 
2012-05-30 EUGM | GAYDOS | Design & Analysis Approaches to Evaluate Cardiovas...
2012-05-30 EUGM | GAYDOS | Design & Analysis Approaches to Evaluate Cardiovas...2012-05-30 EUGM | GAYDOS | Design & Analysis Approaches to Evaluate Cardiovas...
2012-05-30 EUGM | GAYDOS | Design & Analysis Approaches to Evaluate Cardiovas...
Cytel USA
 

More from Cytel USA (20)

From the clinic to the cfo adaptive trials and financial decision making
From the clinic to the cfo   adaptive trials and financial decision makingFrom the clinic to the cfo   adaptive trials and financial decision making
From the clinic to the cfo adaptive trials and financial decision making
 
Eugm 2012 unknown - incivex drug development process overview road to findi...
Eugm 2012   unknown - incivex drug development process overview road to findi...Eugm 2012   unknown - incivex drug development process overview road to findi...
Eugm 2012 unknown - incivex drug development process overview road to findi...
 
Eugm 2012 pritchett - application of adaptive sample size re-estimation in ...
Eugm 2012   pritchett - application of adaptive sample size re-estimation in ...Eugm 2012   pritchett - application of adaptive sample size re-estimation in ...
Eugm 2012 pritchett - application of adaptive sample size re-estimation in ...
 
Eugm 2012 oneill - perspective on the current environment for adaptive clin...
Eugm 2012   oneill - perspective on the current environment for adaptive clin...Eugm 2012   oneill - perspective on the current environment for adaptive clin...
Eugm 2012 oneill - perspective on the current environment for adaptive clin...
 
Eugm 2012 mehta - future plans for east - 2012 eugm
Eugm 2012   mehta - future plans for east - 2012 eugmEugm 2012   mehta - future plans for east - 2012 eugm
Eugm 2012 mehta - future plans for east - 2012 eugm
 
Eugm 2012 jemiai - introduction to east architect
Eugm 2012   jemiai - introduction to east architectEugm 2012   jemiai - introduction to east architect
Eugm 2012 jemiai - introduction to east architect
 
Eugm 2012 gaydos - design and analysis approaches to evaluate cardiovascula...
Eugm 2012   gaydos - design and analysis approaches to evaluate cardiovascula...Eugm 2012   gaydos - design and analysis approaches to evaluate cardiovascula...
Eugm 2012 gaydos - design and analysis approaches to evaluate cardiovascula...
 
Eugm 2012 demets - clinical trials and the impact of regulations
Eugm 2012   demets - clinical trials and the impact of regulationsEugm 2012   demets - clinical trials and the impact of regulations
Eugm 2012 demets - clinical trials and the impact of regulations
 
Eugm 2011 pocock - dm cs-and-adaptive-trials
Eugm 2011   pocock - dm cs-and-adaptive-trialsEugm 2011   pocock - dm cs-and-adaptive-trials
Eugm 2011 pocock - dm cs-and-adaptive-trials
 
Eugm 2011 mehta - execution of adaptive trials operational considerations
Eugm 2011   mehta - execution of adaptive trials operational considerationsEugm 2011   mehta - execution of adaptive trials operational considerations
Eugm 2011 mehta - execution of adaptive trials operational considerations
 
Eugm 2011 mehta - adaptive designs for phase 3 oncology trials
Eugm 2011   mehta - adaptive designs for phase 3 oncology trialsEugm 2011   mehta - adaptive designs for phase 3 oncology trials
Eugm 2011 mehta - adaptive designs for phase 3 oncology trials
 
EUGM 2011 | JEMIAI
EUGM 2011 | JEMIAIEUGM 2011 | JEMIAI
EUGM 2011 | JEMIAI
 
EUGM 2011 | JEHL | group sequential designs with 2 time to event endpoints
EUGM 2011 | JEHL | group sequential designs with 2 time to event endpointsEUGM 2011 | JEHL | group sequential designs with 2 time to event endpoints
EUGM 2011 | JEHL | group sequential designs with 2 time to event endpoints
 
EUGM 2011| Fretault | Use of bayesian approach in phase ii
EUGM 2011| Fretault | Use of bayesian approach in phase iiEUGM 2011| Fretault | Use of bayesian approach in phase ii
EUGM 2011| Fretault | Use of bayesian approach in phase ii
 
EUGM 2011 | DAY | Experiences with interim analyses and dm cs
EUGM 2011 | DAY | Experiences with interim analyses and dm csEUGM 2011 | DAY | Experiences with interim analyses and dm cs
EUGM 2011 | DAY | Experiences with interim analyses and dm cs
 
EUGM 2011 | DARCHY | Deployment & use of east within sanofi r & d
EUGM 2011 | DARCHY | Deployment & use of east within sanofi r & dEUGM 2011 | DARCHY | Deployment & use of east within sanofi r & d
EUGM 2011 | DARCHY | Deployment & use of east within sanofi r & d
 
EUGM 2014 | BEKELE | Adaptive Dose Finding Using Toxicity Probability Intervals
EUGM 2014 | BEKELE | Adaptive Dose Finding Using Toxicity Probability IntervalsEUGM 2014 | BEKELE | Adaptive Dose Finding Using Toxicity Probability Intervals
EUGM 2014 | BEKELE | Adaptive Dose Finding Using Toxicity Probability Intervals
 
EUGM 2014 | BOLOGNESE | Case Studies of Phase 2 Adaptive Dose-Finding Trials
EUGM 2014 | BOLOGNESE | Case Studies of Phase 2 Adaptive Dose-Finding TrialsEUGM 2014 | BOLOGNESE | Case Studies of Phase 2 Adaptive Dose-Finding Trials
EUGM 2014 | BOLOGNESE | Case Studies of Phase 2 Adaptive Dose-Finding Trials
 
A Bayesian Industry Approach to Phase 1 Combination Trials in Oncology
A Bayesian Industry Approach to Phase 1 Combination Trials in OncologyA Bayesian Industry Approach to Phase 1 Combination Trials in Oncology
A Bayesian Industry Approach to Phase 1 Combination Trials in Oncology
 
2012-05-30 EUGM | GAYDOS | Design & Analysis Approaches to Evaluate Cardiovas...
2012-05-30 EUGM | GAYDOS | Design & Analysis Approaches to Evaluate Cardiovas...2012-05-30 EUGM | GAYDOS | Design & Analysis Approaches to Evaluate Cardiovas...
2012-05-30 EUGM | GAYDOS | Design & Analysis Approaches to Evaluate Cardiovas...
 

Recently uploaded

Ocular injury ppt Upendra pal optometrist upums saifai etawah
Ocular injury  ppt  Upendra pal  optometrist upums saifai etawahOcular injury  ppt  Upendra pal  optometrist upums saifai etawah
Ocular injury ppt Upendra pal optometrist upums saifai etawah
pal078100
 
Novas diretrizes da OMS para os cuidados perinatais de mais qualidade
Novas diretrizes da OMS para os cuidados perinatais de mais qualidadeNovas diretrizes da OMS para os cuidados perinatais de mais qualidade
Novas diretrizes da OMS para os cuidados perinatais de mais qualidade
Prof. Marcus Renato de Carvalho
 
basicmodesofventilation2022-220313203758.pdf
basicmodesofventilation2022-220313203758.pdfbasicmodesofventilation2022-220313203758.pdf
basicmodesofventilation2022-220313203758.pdf
aljamhori teaching hospital
 
Maxilla, Mandible & Hyoid Bone & Clinical Correlations by Dr. RIG.pptx
Maxilla, Mandible & Hyoid Bone & Clinical Correlations by Dr. RIG.pptxMaxilla, Mandible & Hyoid Bone & Clinical Correlations by Dr. RIG.pptx
Maxilla, Mandible & Hyoid Bone & Clinical Correlations by Dr. RIG.pptx
Dr. Rabia Inam Gandapore
 
Phone Us ❤85270-49040❤ #ℂall #gIRLS In Surat By Surat @ℂall @Girls Hotel With...
Phone Us ❤85270-49040❤ #ℂall #gIRLS In Surat By Surat @ℂall @Girls Hotel With...Phone Us ❤85270-49040❤ #ℂall #gIRLS In Surat By Surat @ℂall @Girls Hotel With...
Phone Us ❤85270-49040❤ #ℂall #gIRLS In Surat By Surat @ℂall @Girls Hotel With...
Savita Shen $i11
 
Triangles of Neck and Clinical Correlation by Dr. RIG.pptx
Triangles of Neck and Clinical Correlation by Dr. RIG.pptxTriangles of Neck and Clinical Correlation by Dr. RIG.pptx
Triangles of Neck and Clinical Correlation by Dr. RIG.pptx
Dr. Rabia Inam Gandapore
 
Surat @ℂall @Girls ꧁❤8527049040❤꧂@ℂall @Girls Service Vip Top Model Safe
Surat @ℂall @Girls ꧁❤8527049040❤꧂@ℂall @Girls Service Vip Top Model SafeSurat @ℂall @Girls ꧁❤8527049040❤꧂@ℂall @Girls Service Vip Top Model Safe
Surat @ℂall @Girls ꧁❤8527049040❤꧂@ℂall @Girls Service Vip Top Model Safe
Savita Shen $i11
 
Pharynx and Clinical Correlations BY Dr.Rabia Inam Gandapore.pptx
Pharynx and Clinical Correlations BY Dr.Rabia Inam Gandapore.pptxPharynx and Clinical Correlations BY Dr.Rabia Inam Gandapore.pptx
Pharynx and Clinical Correlations BY Dr.Rabia Inam Gandapore.pptx
Dr. Rabia Inam Gandapore
 
Couples presenting to the infertility clinic- Do they really have infertility...
Couples presenting to the infertility clinic- Do they really have infertility...Couples presenting to the infertility clinic- Do they really have infertility...
Couples presenting to the infertility clinic- Do they really have infertility...
Sujoy Dasgupta
 
Prix Galien International 2024 Forum Program
Prix Galien International 2024 Forum ProgramPrix Galien International 2024 Forum Program
Prix Galien International 2024 Forum Program
Levi Shapiro
 
Hemodialysis: Chapter 3, Dialysis Water Unit - Dr.Gawad
Hemodialysis: Chapter 3, Dialysis Water Unit - Dr.GawadHemodialysis: Chapter 3, Dialysis Water Unit - Dr.Gawad
Hemodialysis: Chapter 3, Dialysis Water Unit - Dr.Gawad
NephroTube - Dr.Gawad
 
Ophthalmology Clinical Tests for OSCE exam
Ophthalmology Clinical Tests for OSCE examOphthalmology Clinical Tests for OSCE exam
Ophthalmology Clinical Tests for OSCE exam
KafrELShiekh University
 
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...
Oleg Kshivets
 
The Normal Electrocardiogram - Part I of II
The Normal Electrocardiogram - Part I of IIThe Normal Electrocardiogram - Part I of II
The Normal Electrocardiogram - Part I of II
MedicoseAcademics
 
POST OPERATIVE OLIGURIA and its management
POST OPERATIVE OLIGURIA and its managementPOST OPERATIVE OLIGURIA and its management
POST OPERATIVE OLIGURIA and its management
touseefaziz1
 
Flu Vaccine Alert in Bangalore Karnataka
Flu Vaccine Alert in Bangalore KarnatakaFlu Vaccine Alert in Bangalore Karnataka
Flu Vaccine Alert in Bangalore Karnataka
addon Scans
 
micro teaching on communication m.sc nursing.pdf
micro teaching on communication m.sc nursing.pdfmicro teaching on communication m.sc nursing.pdf
micro teaching on communication m.sc nursing.pdf
Anurag Sharma
 
Charaka Samhita Sutra sthana Chapter 15 Upakalpaniyaadhyaya
Charaka Samhita Sutra sthana Chapter 15 UpakalpaniyaadhyayaCharaka Samhita Sutra sthana Chapter 15 Upakalpaniyaadhyaya
Charaka Samhita Sutra sthana Chapter 15 Upakalpaniyaadhyaya
Dr KHALID B.M
 
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...
GL Anaacs
 
BRACHYTHERAPY OVERVIEW AND APPLICATORS
BRACHYTHERAPY OVERVIEW  AND  APPLICATORSBRACHYTHERAPY OVERVIEW  AND  APPLICATORS
BRACHYTHERAPY OVERVIEW AND APPLICATORS
Krishan Murari
 

Recently uploaded (20)

Ocular injury ppt Upendra pal optometrist upums saifai etawah
Ocular injury  ppt  Upendra pal  optometrist upums saifai etawahOcular injury  ppt  Upendra pal  optometrist upums saifai etawah
Ocular injury ppt Upendra pal optometrist upums saifai etawah
 
Novas diretrizes da OMS para os cuidados perinatais de mais qualidade
Novas diretrizes da OMS para os cuidados perinatais de mais qualidadeNovas diretrizes da OMS para os cuidados perinatais de mais qualidade
Novas diretrizes da OMS para os cuidados perinatais de mais qualidade
 
basicmodesofventilation2022-220313203758.pdf
basicmodesofventilation2022-220313203758.pdfbasicmodesofventilation2022-220313203758.pdf
basicmodesofventilation2022-220313203758.pdf
 
Maxilla, Mandible & Hyoid Bone & Clinical Correlations by Dr. RIG.pptx
Maxilla, Mandible & Hyoid Bone & Clinical Correlations by Dr. RIG.pptxMaxilla, Mandible & Hyoid Bone & Clinical Correlations by Dr. RIG.pptx
Maxilla, Mandible & Hyoid Bone & Clinical Correlations by Dr. RIG.pptx
 
Phone Us ❤85270-49040❤ #ℂall #gIRLS In Surat By Surat @ℂall @Girls Hotel With...
Phone Us ❤85270-49040❤ #ℂall #gIRLS In Surat By Surat @ℂall @Girls Hotel With...Phone Us ❤85270-49040❤ #ℂall #gIRLS In Surat By Surat @ℂall @Girls Hotel With...
Phone Us ❤85270-49040❤ #ℂall #gIRLS In Surat By Surat @ℂall @Girls Hotel With...
 
Triangles of Neck and Clinical Correlation by Dr. RIG.pptx
Triangles of Neck and Clinical Correlation by Dr. RIG.pptxTriangles of Neck and Clinical Correlation by Dr. RIG.pptx
Triangles of Neck and Clinical Correlation by Dr. RIG.pptx
 
Surat @ℂall @Girls ꧁❤8527049040❤꧂@ℂall @Girls Service Vip Top Model Safe
Surat @ℂall @Girls ꧁❤8527049040❤꧂@ℂall @Girls Service Vip Top Model SafeSurat @ℂall @Girls ꧁❤8527049040❤꧂@ℂall @Girls Service Vip Top Model Safe
Surat @ℂall @Girls ꧁❤8527049040❤꧂@ℂall @Girls Service Vip Top Model Safe
 
Pharynx and Clinical Correlations BY Dr.Rabia Inam Gandapore.pptx
Pharynx and Clinical Correlations BY Dr.Rabia Inam Gandapore.pptxPharynx and Clinical Correlations BY Dr.Rabia Inam Gandapore.pptx
Pharynx and Clinical Correlations BY Dr.Rabia Inam Gandapore.pptx
 
Couples presenting to the infertility clinic- Do they really have infertility...
Couples presenting to the infertility clinic- Do they really have infertility...Couples presenting to the infertility clinic- Do they really have infertility...
Couples presenting to the infertility clinic- Do they really have infertility...
 
Prix Galien International 2024 Forum Program
Prix Galien International 2024 Forum ProgramPrix Galien International 2024 Forum Program
Prix Galien International 2024 Forum Program
 
Hemodialysis: Chapter 3, Dialysis Water Unit - Dr.Gawad
Hemodialysis: Chapter 3, Dialysis Water Unit - Dr.GawadHemodialysis: Chapter 3, Dialysis Water Unit - Dr.Gawad
Hemodialysis: Chapter 3, Dialysis Water Unit - Dr.Gawad
 
Ophthalmology Clinical Tests for OSCE exam
Ophthalmology Clinical Tests for OSCE examOphthalmology Clinical Tests for OSCE exam
Ophthalmology Clinical Tests for OSCE exam
 
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...
 
The Normal Electrocardiogram - Part I of II
The Normal Electrocardiogram - Part I of IIThe Normal Electrocardiogram - Part I of II
The Normal Electrocardiogram - Part I of II
 
POST OPERATIVE OLIGURIA and its management
POST OPERATIVE OLIGURIA and its managementPOST OPERATIVE OLIGURIA and its management
POST OPERATIVE OLIGURIA and its management
 
Flu Vaccine Alert in Bangalore Karnataka
Flu Vaccine Alert in Bangalore KarnatakaFlu Vaccine Alert in Bangalore Karnataka
Flu Vaccine Alert in Bangalore Karnataka
 
micro teaching on communication m.sc nursing.pdf
micro teaching on communication m.sc nursing.pdfmicro teaching on communication m.sc nursing.pdf
micro teaching on communication m.sc nursing.pdf
 
Charaka Samhita Sutra sthana Chapter 15 Upakalpaniyaadhyaya
Charaka Samhita Sutra sthana Chapter 15 UpakalpaniyaadhyayaCharaka Samhita Sutra sthana Chapter 15 Upakalpaniyaadhyaya
Charaka Samhita Sutra sthana Chapter 15 Upakalpaniyaadhyaya
 
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...
 
BRACHYTHERAPY OVERVIEW AND APPLICATORS
BRACHYTHERAPY OVERVIEW  AND  APPLICATORSBRACHYTHERAPY OVERVIEW  AND  APPLICATORS
BRACHYTHERAPY OVERVIEW AND APPLICATORS
 

Clinical Proof of Concept (PoC)

  • 2. OutlineOutline  Exploratory Drug Development  Defining POC Defining POC  Improving Probability of Success with Greater Emphasis on POCp  Improving POC Through Better Patient Selection  Practical Considerations of Patient Selection Strategies  Summary/conclusion
  • 3. Exploratory Drug Development- Phase I/IIExploratory Drug Development Phase I/II P li i l Phase I (Fi t i Phase II (P f f Ph III R i t tiPre-clinical (First-in- Human) (Proof-of- Concept) Phase III Registration • Evaluate safety/PK E l i f • Establish POC Inform phase 3 Phase 1 Phase II S f t Effi ( • Inform phase 2 • Early signs of efficacy • Inform phase 2 • Inform phase 3 Endpoints • Safety • PK • Efficacy (response rates, time-to-event) Outcomes • Dose/regimen for Phase 2 and beyond • Efficacy sufficient for Phase 3/ registration Design • Dose-escalation • Single-arm • Randomized Patient population • Unrestricted • Restricted to indication Sample size • 30-50 • 75-150
  • 4. Success Rates from First-in-Man to RegistrationRegistration Kola & Landis (2004) Nature Rev Drug Disc
  • 5. Success Rates by Phase of DevelopmentSuccess Rates by Phase of Development Kola & Landis (2004) Nature Rev Drug Disc
  • 6. Cost of Drug Development by PhaseCost of Drug Development by Phase Roy A (2012) Manhattan Institute
  • 7. Defining POCDefining POC  PhRMA recommendation: “POC is the earliest point in drug development processPOC is the earliest point in drug development process at which the weight of evidence suggests that it is “reasonably likely” that the key attributes for success are present and the key causes of failure absent”  Varies by person, project, candidate, etc…
  • 8. Goals by end of PoCGoals by end of PoC P li i l Phase I (Fi t i Phase II (P f f Ph III R i t tiPre-clinical (First-in- Human) (Proof-of- Concept) Phase III Registration • Establish POC Inform phase 3 We’d like to know • Inform phase 3 We d like to know  Best dose and regimen (safety driven)  Indications  Administered in combination with what, if anything  Patients who will respond Pfizer Confidential │ 8  Degree of efficacy
  • 9. POC Essential ElementsPOC Essential Elements  Define essential elements of target product profile  Determine level of risk tolerance for POC Determine level of risk tolerance for POC  Low weight of evidence when consequences of being wrong are benign and benefits of speed are high  High weight of evidence where consequences of wrong High weight of evidence where consequences of wrong POC are severe  Determine which elements of POC are already “reasonably likely” on basis of prior information  Determine which of the remaining elements are not likely to be significant threats to the programlikely to be significant threats to the program  Determine which of the still remaining elements cannot be practically evaluated or changed
  • 10. Decision Criteria for POCDecision Criteria for POC  Based on outcome  Set required effect size (∆) lower reference value Set required effect size (∆), lower reference value (LRV) below which, drug would not have value HR TV HR MAV HR ≤ 0.63 & 0.63 0.80 1.00 PFS Hazard ratio HR ≤ 0.63 & Upper bound of 90% CI < 1 & Upper bound of 50% CI ≤ 0.80 GO to phase III NO GO HR≥ 0.80 Re‐evaluate 1-sided significance level of 0.10 and 80% power GO to phase III NO GO
  • 11. Examples of Oncology POC TrialsExamples of Oncology POC Trials  Design  Randomized in same patient population as phase III/registration  Standard-of-care (SOC) +/- Experimental compound  Experimental compound vs. SOC  Single- arm trial  Compare with historical controls  Endpointsp  Same as endpoints which will be used in phase III/Registration  Time-to-event (OS, PFS)  PFS typically favored due to shorter trial; need to correlate withyp y ; registrational endpoint (usually OS)  Sample sizes  Typically based on 1-sided α 0.05, 80% poweryp y , p  75‐80 patients per arm of randomized study
  • 12. Attrition of Last-Stage Drug DevelopmentAttrition of Last Stage Drug Development Adapted from Arrowsmith 2011
  • 13. Patient Selection Strategies to Reduce Attrition in Phase 3Attrition in Phase 3  Advantages to using biomarker to identify patients likely to benefitpatients likely to benefit  Smaller sample sizes required  More expeditious path to reach Go/No Go to phase 3  Less expensive  Avoids treating patients with little opportunity of benefitting  Success of biomarker selection dependent on: Success of biomarker selection dependent on:  Prevalence of marker  Effect size  Clinical performance of diagnostic assay
  • 14. Patient Selection StrategiesPatient Selection Strategies  Prospectively select biomarker positive patients  Requires confidence that biomarker is predictive of Requires confidence that biomarker is predictive of outcome  Need for clinical data in biomarker-negative patients  Enrich for biomarker positive patients in otherwise all- comers trial  Retrospective analysis of response based on Retrospective analysis of response based on biomarker  Efficacy signal may be diluted by biomarker-negative patients  Adaptive designs to incorporate biomarker information in Phase 2information in Phase 2
  • 15. Patient Selection Strategies  Incorporation of stratified medicine approach leads to increase in eNPV versus all-comers Patient Selection Strategies • Increased eNPV when patient selection used prospectively (e.g. trastuzumab) • Negative effects of eNPV when patient selection used retrospectively (e.g. panitumumab) Trusheim et. al. 2011
  • 16. Evolution of Non-Small Cell Lung Cancer TreatmentTreatment Martin Reck , et. al., The Lancet, Volume 382, Issue 9893, 2013, 709 - 719 Reck et. al. 2013
  • 17. Clinical Experience in 1st L NSCLC: All- comers vs. patient selectioncomers vs. patient selection Patient Efficacy Response Progression-free Overall survival: mo Population Treatment Sample Size Rate: % survival: mo Overall survival: mo Paclitaxel- cisplatin 1599 23-25 (v. 12) 4.3-4.9 (v. 2.7) 9.3-10.0 (v. 7.4) Gemcitabine- 2522 26 5.2 9.0 All-comers cisplatin 2522 (v. 10) (v. 3.7) (v. 7.6) Gefitinib (EGFR- inhibitor) + 31,093 41,037 51,059 No improvement v. chemotherapy chemotherapy 61,172 EGFR- mutated Gefitinib (EGFR- inhibitor) v. 7261 71 (v. 47) 9.5 (v. 6.3) 21.6 (v. 21.9) (15% NSCLC) chemotherapy Erlotinib v. chemotherapy 8174 65 (v. 16) 10.4 (v. 5.2) 22.9 (v. 19.5) ALK- Crizotinib 65 7 7 rearranged (5% NSCLC) (ALK-inhibitor) 9347 65 (v. 20) 7.7 (v. 3.0) Not available 1Taxol® package insert; 2Gemzar® package insert 3Giaccone et. al. (2004);  4Herbst et. al. (2004);  5Herbst et. al. (2005); 6Getzemeier et. al. (2007);  7Iressa® package insert; 8Tarceva® package insert
  • 18. Practical considerationsPractical considerations  Need for sufficient patient samples  CLIA-certified assays needed for patient selection CLIA-certified assays needed for patient selection  Establishment of cut-offs for biomarker expression  Prevalence of biomarker-positive population Prevalence of biomarker positive population  Evidence for correlation between biomarker expression and outcomep  Seemless decision points if adaptive trial design used  Prevent extended slowing or stopping of enrollment during study
  • 19. Summary and ConclusionsSummary and Conclusions  High cost of attrition in phase 3 setting is shifting emphasis to better design of phase 2 trialsemphasis to better design of phase 2 trials  Establishing appropriate POC in exploratory development critical for improving probability of success in phase 3  Recent shift in oncology drug development toward f ti ti t l ti i tt t tfocus on prospective patient selection in attempts to address poor overall success rates  Adaptive study designs being considered to Adaptive study designs being considered to efficiently use biomarker data  Practical considerations need to be addressed to ensure success
  • 20. ReferencesReferences  Arrowsmith J. Phase II failures: 2008-2010. Nat Rev Drug Disc (2011);10:1  Cartwright ME, Cohen S, Fleishaker JC, et. al. Proof of concept: a PhRMA position paper with recommendations for best practice. Nature (2010);87;278 DiM i JA H RW G b ki HG Th i f i ti ti t f d DiMasi JA, Hansen RW, Grabowski HG. The price of innovation: new estimates of drug development costs. J Health Econ (2003);22:151  Gatzemeier U, Pluzanska A, Szczesna A, et. al. Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non-small-cell lung cancer: the Tarceva lung cancer investigation trial. J Clin Oncol (2007);25;1545 G G S C G f Giaccone G, Herbst RS, Manegold C, et. al. Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial-INTACT 1. J Clin Oncol (2004);22:777  Herbst RS, Giaccone G, Schiller JH, et. al. Gefitinib in combination with paclitaxel and carboplatin in advanced non-small cell lung cancer: a phase III trial- INTACT 2. J Clin Oncol (2004);22:785  Herbst RS, Prager D, Hermann R, et. al. TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI- 774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol (2005);23:5892  Kola I and Landis J. Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Disc (2004);3:711  Reck M, Heigner DF, Mak T, et. al. Management of non-small-cell lung cancer: recent developments. Lancet (2013);382:709  Roy SA. Stifling new cures: The true cost of lengthy clinical drug trials. Project FDA (2012). Manhattan Institute for Policy Research. http://www.manhattan-institute.org/html/fda_05.htm  Trusheim MR Burgess B Hu SX et al Quantifying factors for the success of stratified medicine Trusheim MR, Burgess B, Hu SX, et.al. Quantifying factors for the success of stratified medicine. Nat Rev Drug Disc (2011);10:817