Post on 12-Apr-2017
IMAGING ENDPOINTS FOR CLINICAL TRIALS Kenneth G. Faulkner, Ph.D., Corporate Vice President, Medical Imaging
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OUTLINE
• Selecting Imaging Endpoints• Exploratory
• Efficacy
• Safety
• Operational Considerations
• Regulatory Requirements
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• Early Efficacy Signal
• Early Safety Signal
• Mechanism of Action
• Non Target Tissues
• Adverse Effects
• Post Approval Surveillance
• Primary
• Secondary
• Eligibility
• Regulatory Approval
• Safety Requirement
• Go to Market Data
EXPLORATORY
IMAGING IN CLINICAL TRIALS
SAFETYEFFICACY
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DEVELOPMENT INDICATIONS (PHASE I – III)
Medtrack: December 2014
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RECISTRESPONSE EVALUATION CRITERIA IN SOLID TUMORS
RECIST is simple.Using RECIST is not.
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IMAGE CONTRAST AND TIMING
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RECIST: LONGEST DIAMETER DETERMINATION
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RECIST: FOLLOW-UP ASSESSMENT
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ONCOLOGY: IMMUNE RESPONSE
Baseline
Timepoint 1
Timepoint 2
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IMAGING FOR RHEUMATOID ARTHRITIS
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MUSCULOSKELETAL IMAGING
DXA
Body composition and bone mineral density (BMD)
CT
Abdominal fat distribution
X-ray
Rheumatoid Arthritis, Gout, Bone AgeOsteoarthritis
Kelgren-Lawrence, JSW
Ankylosing Spondylitis mSASS
Fracture Healing
Rheumatoid Arthritis, Gout RAMRIS
MRI
Ankylosing SpondylitisASspiMRI, SPARCC
Rheumatoid Arthritis
Osteoarthritis
Spinal Device
QCT Volumetric bone density
Vertebral Fracture
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ALZHEIMER’S DISEASE
Normal
AD
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NEUROLOGY - PATIENT ELIGIBILITY
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CARDIAC FUNCTION
Echocardiography MUGA
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CAROTID INTIMA-MEDIA THICKNESS (CIMT)
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OPHTHALMOLOGY
RESPIRATORYGASTROINTESTINAL
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Acquisition and Transmission
Image Preparation Review Results
Quality Oversight
Collect and Hold Read Ready Full Service
OPERATIONAL DESIGN
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REGULATORY STANDARDSFDA DRAFT GUIDANCE AUGUST 2011
• Use of Clinical Trial Standard• Clinical Trial Standard features “exceed
those typically used in medical practice”
• Define both image acquisition and interpretation standards
• Central interpretation vs. Local (site) interpretation
• Imaging Charter• Detailed description of imaging
acquisition and interpretation methodology to be used
• Submission of charter together with clinical protocol “encouraged”
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IMAGE ACQUISITION STANDARDS
• Equipment and technical settings
• Role of site imaging technicians
• Use of phantoms and other quality monitoring tools
• Patient preparation and positioning
• Site qualification procedures
• Data storage and transfer
• Use of imaging agents (if required)
FDA DRAFT GUIDANCE AUGUST 2011
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IMAGE INTERPRETATION STANDARDS
• Image format, transfer, tracking and documentation
• Initial quality assessment
• Selection of images for interpretation
• Reader training and qualification
• Details of read process• Workflow (i.e. single vs double read, adjudication process)
• Description of electronic tools
• Case report forms
• Data lock procedures
FDA DRAFT GUIDANCE AUGUST 2011
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REGULATORY CONSIDERATIONS
FDA EMA JAPAN PMDA
Accelerated / Progressive approval frameworks ✓ ✓Greater focus on post-approval drug safety ✓ ✓ ✓Focus on innovative medicines ✓ ✓ ✓Acceptance of biosimilars ✓ ✓ ✓Adaptive study designs ✓ ✓Agile interactions with sponsors ✓ ✓ ✓Global outreach and collaboration ✓ ✓ ✓Performance/Accountability (user fees, metrics) ✓ ✓ ✓
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OUTLINE
• Selecting Imaging Endpoints• Exploratory
• Efficacy
• Safety
• Operational Considerations
• Regulatory Requirements
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BOSTON, MASSACHUSETTS
THANK YOUKen Faulkner, Ph.D.Ken.Faulkner@PAREXEL.com
www.PAREXEL.comwww.recist.com