EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi...
Transcript of EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi...
![Page 1: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/1.jpg)
EVOLUTION OF CLINICAL TRIALS
Prof. Dr. Hamdi AkanAnkara University Faculty of Medicine
Department of Hematology
Clinical Trials UnitClinical Research Association
![Page 2: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/2.jpg)
Two Pathways of Evolution
![Page 3: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/3.jpg)
Two Pathways of Evolution
![Page 4: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/4.jpg)
Frieden,T.R.etal.JAMA2010;0:jama.2010.1554v1-2.
EvolutionofHumanSubjectsResearchandGuidelines
![Page 5: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/5.jpg)
HELSINKI
![Page 6: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/6.jpg)
![Page 7: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/7.jpg)
JAMES LIND (1716-1794)
1740CommodoreGeorgeAnsonledasquadronofeightshipsonamissionforSpain'sPacificpossessions.
ReturnedtoBritainin1744
1,854 188
![Page 8: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/8.jpg)
Cider Vinegar
Sea water Orange,Lemon
Sulfuricacid
HerbalTea
![Page 9: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/9.jpg)
![Page 10: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/10.jpg)
1537 - An unintended clinical trial by surgeon Ambroise Pare
Battlefield wounded soldiers
Boiling Oilyolks of eggs,
oil of roses turpentine
![Page 11: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/11.jpg)
1863 - First controlled clinical study by Austin Flint
Rheumatism(13pts)
HerbalRemedy(placeboic remedy)
EstablishedTreatment
![Page 12: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/12.jpg)
1943 - The First Double blind Controlled Trial Patulin for Common Cold
COMMONCOLDTheMedicalResearchCouncil(MRC)UK
Patulin (extractofPenicilliumpatulinum)
ControlGroup
DOUBLEBLIND
NORANDOMIZATION
![Page 13: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/13.jpg)
TheMedicalDepartmentoftheUnitedStatesArmyintheWorldWar.Communicable andOtherDiseases.Washington: U.S.GovernmentPrintingOffice,1928, vol.IX,pp.171-202.
II. WORLD WAR
IncidenceofTuberculosis
1948 - First Randomized Clinical Trial
![Page 14: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/14.jpg)
• ThefirstrandomizedtrialwaspublishedinBMJin1948.
• ThetrialwasabouttheuseofStreptomycininsoldierswithTB.
• Theaimoftherandomizationwasnotscientific.VeryfewStreptomycin,butalotofTBcases.
MRCStreptomycininTuberculosis TrialsCommittee.Streptomycintreatmentofpulmonarytuberculosis.BMJ.1948;2:769–83.
![Page 15: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/15.jpg)
15
![Page 16: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/16.jpg)
FDABasedterminology
https://www.pinterest.com/pin/466474473878366162/
![Page 17: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/17.jpg)
%9.6
![Page 18: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/18.jpg)
WHY?WHYDOWENEEDTOMODIFYTHIS?
![Page 19: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/19.jpg)
• TIME & COST
• EMERGING DISEASES
• ORPHAN DISEASES
• PERSONALIZED MEDICINE
TIME & COST
PERSONALIZED MEDICINE
EMERGING DISEASES
ORPHAN DISEASES
![Page 20: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/20.jpg)
The cost of a new drug approval in USA500.000.000 – 1.000.000.000 USD.
COST
![Page 21: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/21.jpg)
• 12
>12YEARS
![Page 22: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/22.jpg)
![Page 23: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/23.jpg)
![Page 24: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/24.jpg)
HOW?
![Page 25: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/25.jpg)
METHODOLOGY
AUTHORITYREVIEW
![Page 26: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/26.jpg)
FDA EXPEDITED REVIEW
•Accelerated Approval
• Priority Review
• Fast Track
•Breakthrough Therapy
Adrugcandidatethataddressesaseriousconditionandwhichmayofferameaningfuladvantageoveravailabletherapies.Usesasurrogateendpoint.
Designedforaveryseriouscondition,thetrialshavebeencompletedwithansignificantimprovement.Reviewtimeisreducedfrom10monthsdownto6months.
Fordrugcandidatesintendedtotreataseriousconditionandthatdemonstratedinnon-clinicalstudiesthepotentialtoaddressanunmetmedicalneed.
Adrugcandidatethatisintendedtotreataseriousconditionand,alsohaspreliminaryclinicalevidencetosuggestitmaybeasubstantialimprovementoveravailabletherapies.
Alloftheseprogramsareaimedatseriousandlife-threateningdiseases.
![Page 27: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/27.jpg)
AUTHORITYREVIEW
METHODOLOGY
HOW?
CHANGINGTHEMETHODOLOGY
![Page 28: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/28.jpg)
1. USING DIFFERENT/SURROGATE END POINT/S
2. DEVELOPING NEW BIOMARKERS
3. BASKET/UMBRELLA TRIALS
4. ADAPTIVE DESIGN
5. REAL LIFE DATA (BIG DATA)
![Page 29: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/29.jpg)
SURROGATE END POINT VERSUS
CLINICAL END POINT
![Page 30: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/30.jpg)
Surrogate end-point:
indicators of a change in the disease that are likely to predict a clinical benefit
• provide an estimate of how well a drug will treat a disease or condition
![Page 31: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/31.jpg)
28 MAY 2001
![Page 32: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/32.jpg)
7-10YEARS
CLINICALENDPOINT
![Page 33: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/33.jpg)
Resultsfromprospectivetrialssuggestthat imatinib therapycanbesuccessfullydiscontinuedinCMLpatientswithdeepandsustainedmolecularresponses(LancetOncology2010;11:1029,Blood2013;122:515)
bcr-abl
SURROGATEENDPOINT
![Page 34: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/34.jpg)
VALIDATION of SURROGATE ENDPOINTS
TREATMENT SURROGATEENDPOINT
CLINICALENDPOINT
Effectsoftreatmentonsurrogateandclinicalendpointmustbecorrelated
Surrogateandclinicalendpointsmustbecorrelated
![Page 35: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/35.jpg)
• One-third of cancer drugs approved in the recent years come to market one the basis of improvement in overall survival, while two-thirds are approved based on a a surrogate endpoint.
• Not only targeted therapies but also traditional diseases benefit form surrogate endpoints:
Diabetes Mellitus and HbA1c
Mailankody S,PrasadV.OverallSurvival inCancerDrugTrialsasaNewSurrogateEndPointforOverallSurvival intheRealWorld.JAMAOncol.2017;3(7):889-890.
![Page 36: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/36.jpg)
NEW BIOMARKERS
![Page 37: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/37.jpg)
NEWBIOMARKER
TargetedTherapy/Personalized
Medicinepredictthepopulation thatwillbemostlikelytobenefitfromadrug
Surrogateendpoint
showactivityorcausalityinadisease
![Page 38: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/38.jpg)
FINDING THE APPROPRIATE BIOMARKER
• Consequtive testing strategy: First find the drug, then thebiomarker
Drug Clinical Trial
“Marker”?
Result
![Page 39: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/39.jpg)
Biomarkers in Clinical Research - 1
• Biomarker as a stratification parameter
Drug Clinical TrialResult
“Marker”?Marker+
Marker-
![Page 40: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/40.jpg)
• Biomarker as a randomization strategy
Clinical Trial Result“Marker”?
Marker+
Marker-
Control
Drug
Control
Drug
Biomarkers in Clinical Research - 2
![Page 41: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/41.jpg)
• Biomarker as a target
Clinical Trial Result“Marker”?
Marker+
Marker-
Control
Drug
Biomarkers in Clinical Research - 3
![Page 42: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/42.jpg)
www.clinicaltrials.gov
![Page 43: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/43.jpg)
EVENT DRIVEN TRIALS
• The endpoint is not the DURATION of the study but an EVENT
• The power of the study depends on the observed EVENTS
• Early termination or prolongation of a study is possible
NOT
“This study will terminate on February 2019”
BUT
“This study will terminate after the observation of 120 EVENTS”
![Page 44: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/44.jpg)
UMBRELLA TRIALS
BASKET TRIALS
![Page 45: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/45.jpg)
ONEDISEASEOne ormorecommonmutations
Smallnumberofpatientsfor
everymutation
Allpatientswiththe
diagnosisinthetrial
Checkforthemutations
Givetargetedtherapy
appropriateforeachmutation
UMBRELLA TRIAL/MASTER TRIAL
AnysuccessinPhaseIIdirectlyproceedstoPhaseIIIinthesamepatients
![Page 46: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/46.jpg)
![Page 47: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/47.jpg)
ALL IN A BASKET
![Page 48: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/48.jpg)
DIFFERENTDIAGNOSESSAMEMUTATION/S
DIFFERENTTREATMENTFOREVERYSINGLE
MUTATION
![Page 49: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/49.jpg)
![Page 50: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/50.jpg)
Non-smallcellLungcaSmall-cell Lungca
Thymic malignancies
Treatmentforoneofthe5differentbiomarkers
Erlotinib – EGFRSelumetinib – KRAS,NRAS..MK2206 - PIK3CA,AKT..Lapatinic – ERBb2Sunitinib – KIT,PRGFRA
Standart caretherapy
NCI-MPACT
![Page 51: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/51.jpg)
ADAPTIVE DESIGN
or
learning while walking
![Page 52: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/52.jpg)
Modification of one or more specified aspects of the study design and hypotheses based on
analysis of data during the study
Revisions Based on Information From a Study External Source is not an adaptive design
![Page 53: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/53.jpg)
• Definethetimepoints
• Fullyblindedorunblindedanalysis
• Planrevisionsandadaptationsaftertheanalysis
INTERIM ANALYSIS
ADAPTIVE DESIGN
STUDYENDPOINT/SDISCONTINUATIONRATES
StudyeligibilityRandomizationprocedureTreatmentregimensSamplesize(earlytermination)DatacollectiontimepointsPrimaryendpointSecondaryendpointsAnalyticmethodology
![Page 54: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/54.jpg)
PROBLEMS
• Adaptation leading to a false conclusion that the treatment is effective – Type I error
ANALYTICALBLINDING
INVESTIGATORSHIELDING
![Page 55: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/55.jpg)
![Page 56: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/56.jpg)
ENRICHEMENT STRATEGIES
![Page 57: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/57.jpg)
Prospective use of any patient characteristic to select a study population in which detection of a drug effect) is more likely than it would be in an unselected population.
Selection:
• demographic,
• pathophysiologic,
• historical,
• genetic or proteomic,
• clinical,
• psychological characteristics
![Page 58: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/58.jpg)
CARDIOVASCULAR DISEASE
Severe cardiovascular disease (2 or more coronary artery occlusion)
Severity of the illness + other factors that can indicate increased risk:
• history of recent myocardial infarction or stroke;
• the presence of concomitant illness such as diabetes, hypertension, or hyperlipidemia;
• very high LDL cholesterol, low HDL cholesterol and high C-reactive protein (CRP)
considerably reduces the sample size (the enalapril and statin trials)
- Largestudypopulation- Moderateorslighteffect
- Smallstudypopulation- Distinctiveeffect
![Page 59: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/59.jpg)
![Page 60: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/60.jpg)
1. USING DIFFERENT/SURROGATE END POINT/S
2. DEVELOPING NEW BIOMARKERS
3. PUTTING ALL IN A BASKET
4. ADAPTIVE DESIGN
5. ENRICHEMENT STRATEGIES
6. REAL LIFE DATA (BIG DATA)
![Page 61: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/61.jpg)
REFLECTING REAL LIFE
Mega–Trials:ClinicalResearchconductedonmorethan10.000participants
• HIGHBUDGET• LONGTERM• NEEDSDETAILEDORGANISATION• NEWAPPROACHESSUCHASVIRTUALorRISKBASED
MONITORIZATIONReallyreflectsreallife?
![Page 62: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/62.jpg)
REAL LIFE DATA – BIG DATA
• DataBase:Cross-sectionalandhorizontaldata• Surveysofpatientsandsociety:Dataforepidemiologicstudies• Patientmonitorisation records:Forstudiesinvolvingpatientcare• Observationsfromcohortstudies: Themaindataforreallifestudies• Pragmaticclinicalresearch: Clinicalresearchmimickingreallife:debatable• Diseaseregistries:Continuousrecordingandevaluationofspecificindicationsinspecificcenter/centers
![Page 63: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/63.jpg)
PROBLEMS
• Lackofresources/data(countriesanddata)
• Lowsensitivity– Ambigious diagnosisandoutcome
•Missingdata
• ConfoundingandBias
![Page 64: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/64.jpg)
TECHNOLOGICAL EVOLUTION1980 1990 2000
ISOLATEDSYSTEMS
Clinical TrialManagementSystems(CTMS),ElectronicClinical OutcomesAssessments (eCOA)
INTEGRATEDSYSTEMS
InteractiveResponse Technology (IRT)
Single sign-on(SSO)Risk-basedmonitoring (RBM)Patient EngagementeSourceWearable devicesElectronicdrug accountability
![Page 65: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/65.jpg)
![Page 66: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/66.jpg)
![Page 67: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/67.jpg)
INTERNET OF THINGS
![Page 68: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/68.jpg)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981575/
![Page 69: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/69.jpg)
Applicationsofwearables inthefitnessandclinicalresearchcontext(Source: Biotaware)
![Page 70: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/70.jpg)
https://knect365.com/clinical-trials-innovation/article/f3ebedd3-1d69-4d42-bf70-d0f8d44f7c24/internet-of-things-clinical-trials-challenges-opportunities
![Page 71: EVOLUTION OF CLINICAL TRIALS - 👍 #iyileşeceğiz · EVOLUTION OF CLINICAL TRIALS Prof. Dr. Hamdi Akan Ankara University Faculty of Medicine Departmentof Hematology ClinicalTrials](https://reader034.fdocuments.in/reader034/viewer/2022042313/5edf8330ad6a402d666adadc/html5/thumbnails/71.jpg)
THANKS FOR LISTENING