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