2009 Strategic Planning Meeting SNM Clinical Trials Network

Chicago, IL

Wednesday, September 30, 2009

AGENDA

Item Time Discussion

Leaders

BREAKFAST –

Welcome and Introductions 8:00am – 8:15 M. Graham

2009 Summary of Progress 8:15am – 9:30am M. Graham

Phantom Program P. Christian

Imaging Site Validation/Registry J. Hoffman

Education Programs M. Howlett

Database Committee J. Sunderland

Manufacturing Registry P. Conti

Questions and Discussion

BREAK 9:30am – 9:45am

Industry – Challenges/Lessons Learned 9:45am – 12:00pm P. Conti

Bristol-Myers Squibb: Observations Wendy Hayes

Isotope Shortage and Relevance to Clinical

Trials P. Conti

LUNCH 12:00pm – 1:00pm

Discussion of Next Multicenter IND 1:00pm – 2:00pm M. Graham

BREAK 2:00pm – 2:15pm

Three-Year Goals and Draft Work Plan 2:15pm – 4:00pm M. Graham

SNM Draft 3yr. Work Plan M. Ryan

Trial Design / Protocol Development P. Conti

A. Shields

Targets and Marketing of Network M. Ryan

Wrap-Up and Next Steps 4:00pm – 5:00pm P. Conti

2009 Summary of Progress

• First SNM multicenter IND for an investigational imaging biomarker

• First two founding members from the pharmaceutical development community on board

• 200+ members of both the imaging site and manufacturers registries

• Over 25% participation from outside the U.S.• Development and launch of a clinical oncology phantom

program• Many on-going educational activities to promote the

Network and advance the awareness and understanding of the “Practice of Clinical Trials” within the imaging community

Key Accomplishments

1. Organize multi-site clinical trials to gather standardized and harmonized imaging data that will lead to expanded use and validation of imaging biomarkers for therapeutic trials

2. Provide safety and efficacy data of imaging biomarkers through a centralized IND, potentially useful for eventual approval of such as as diagnostics

3. Organize a manufacturing registry for production of and access to imaging biomarkers

4. Provide a registry of qualified and certified imaging centers

Major Goals

Phantom Sub-Committee

Chair: Paul Christian, CNMT, BS, PET

Purpose:Management of phantom program for site qualification

Phantom Sub-Committee

Clinical Simulation Phantoms

Evaluate: Image performance-Acquisition-Processing-Interpretation

Lesion detectionSUV measurements

Purpose of PET phantom-Uniformity-Resolution -Contrast-Noise-Quantitative accuracy -PET/CT alignment-Attenuation correction

Accomplishments:1. Development of phantom qualification process2. Phantom acquisition3. Phantom review and quality assurance testing4. Administration of FLT, chest phantom demonstration

project

Phantom Sub-Committee

Submit Images and SUV Data

Site Phantom Qualification

PET Qualification Chest Phantom

0

0.5

1

1.5

2

2.5

3

3.5

0 1 2 3 4 5 6 7 8 9

Lesion Number

SU

Vm

ax

Series1Series2Series3Series4Series5Series6Series7

PET Qualification Chest Phantom

0

0.5

1

1.5

2

2.5

3

3.5

0 1 2 3 4 5 6 7 8 9

Lesion Number

SU

Vm

ax

Series1Series2Series3Series4Series5Series6Series7

PET Qualification Chest Phantom

0

0.5

1

1.5

2

2.5

3

3.5

0 1 2 3 4 5 6 7 8 9

Lesion Number

SU

Vm

ax

Series1Series2Series3Series4Series5Series6Series7

Assess:

Acquisition protocolAccuracy of doseReconstruction/filterImage qualityPET/CT alignmentAttenuation correctionImage noiseImage contrastMD visual assessmentLesion detectabilitySUV accuracyDICOM transfer validValidation of SUV DICOM

2010 Goals:1. Streamline phantom qualification program2. Develop process for long term maintenance and

administration of phantom site qualification3. Develop additional phantom programs including brain

and cardiac

Phantom Sub-Committee

Site Validation and Monitoring Committee

Chair: John M. Hoffman, M.D.

Purpose:• Development and management of imaging site

qualification and validation program• Develop a process whereby pharmaceutical partners

have the information to make decisions about which imaging sites have the infrastructure, resources, experience, and knowledge to perform imaging as it relates to pharmaceutical trials

Site Validation and Monitoring Committee

Accomplishments:1. Development of site qualification and validation process

including:– Available imaging equipment inventory for trials– Assessment of quality assurance programs in place at sites– Review of personnel and their qualifications– Evaluation of research related training of all personnel at site– Assessment of experience of site to perform imaging on therapeutic

trials – Regulatory infrastructure in place to perform imaging studies

2. Development and refinement of site qualification and validation forms

3. Process for evaluation of site “credentials”

Site Validation and Monitoring Committee

2010 Goals:1. Streamline site qualification and validation program

• Move to a web based process to obtain information• Beta and several other site validation of the process• Work with pharma to assure that the “required information” is

being obtained for this important process

2. Develop process for long term maintenance and administration of site qualification and validation process

3. Develop rating system for evaluation of imaging sites?4. Work with pharmaceutical partners to refine the process

to assure that the needed information is being assessed for partner to best choose sites for imaging

Site Validation and Monitoring Committee

Site Validation and Monitoring Committee

Education Update

• Standardization across clinical sites

• Research related training for technologists– Good Clinical Practice in Research– Imaging specific

Summary of Identified Needs

1. Develop a certificate program for technologists to

be trained in running clinical trials/clinical research

programs

– Create curriculum outline– Prepare presentations, videos, or webinar

presentations to cover all pertinent content with personnel

– Develop tracking metrics to verify completion of training by individuals

Development Plans

2. Provide research (imaging specific) training

materials to potential trial site personnel in registry

– Create curriculum outline– Prepare presentations, videos, or webinar

presentations to cover all pertinent content with personnel– Develop tracking metrics to verify completion of training by

individuals– Develop feedback mechanism for ongoing review

and improvement of presentations and materials

***This task assigned to Tech Educator Sub-Committee

Development Plans

3. Create enduring materials for use at clinical trial sites to provide reinforcement of educational programs– Online webinars available year round– Educational booklets– Poster presentations at sectional meetings– DVDs

Development Plans

4. Explore collaboration with research organizations that currently provide research related training– ACRP (Clinical Research Coordinator Training)– Drug Information Association (DIA)

Development Plans

5. Develop physician oriented clinical research programs to include the following components:

– FDA approval process– Review of Good Clinical Practice– Quality assurance in medical trials

Development Plans

Tech Educators Sub-Committee

Education Update

Courses for Technologists:

1. Focus on CTN 106: “Stick to it: Camera and Radiopharmacy” (2 Hour)

2. Focus on CTN 107: “O Say can I See your QC” (1 Hour)3. Focus on CTN 108: “The Importance of SOPs in Clinical

Trials” (1 Hour)

Educational Offerings

All courses offered online (continuous) and at SNM meetings

Timelines:• August 31 – First Draft of Courses due• September 14 – Proof reading complete• September 30 – Group review of courses• October 30 – Final Format of Courses• November 15 – Completion of VOICE and CEU credits• November 15 – Completion of Pre/Post Assessments• November 30 – Completion of final web format• December 15– Courses go live on CTN

Educational Offerings

1. Online educational offerings for technologists (continual)

2. Live course presentations at meetings3. Brochures and poster presentations at sectional

meetings

Delivery Channels

• Panel 1: Potential Role of Imaging Biomarkers in Development of Neurological Therapeutics

• Panel 2: A Regulatory Perspective on the Challenges of Standardization and Harmonization in Multicenter Imaging Clinical Trials

• Panel 3: Removing the Barriers to Use Imaging Biomarkers in Clinical Research : Progress of the SNM Clinical Trials Network

CMOD

Plans for Meetings

WMIC

Introduction to the SNM Clinical Trials NetworkGeorge Mills, MD, MBA

Distributed Manufacturing of PET Radiopharmaceuticals and Multicenter Clinical Trials Participation

Sally Schwarz, PhD, Washington University

Development of New Imaging Approaches for Drug Development and Treatment Monitoring

Anthony Shields, MD, PhD

Plans for Meetings

Plans for Meetings

Summit 2010: Molecular Imaging in Clinical Trials

SNM Mid-Winter Meeting

Session I – Current Challenges of Imaging in

Therapeutic Clinical Trials

Session II – Critical Elements of Imaging in High

Quality Multicenter Clinical Research

Database Sub-Committee

Chair: John Sunderland, Ph. D.

Purpose:• Development of centralized database to incorporate:

– Imaging site registrations– Radiopharmaceutical manufacturer registrations– Site validation

• Optimize database to maximize utility of CTN for Pharma, SNM, and other stakeholders

Database Sub-Committee

Accomplishments:

1. Database design

1. Integration of Clinical Trial Network Database with SNM Membership Database

1. First iteration of the Clinical Trials Network Database web application for data entry completed

Database Sub-Committee

CTN Database Structure and Flow

2010 Goals:

1. Complete database for full scale launch

1. Deliver database to SNM for long term maintenance

1. Fine-tune database entry

2. Finalize standard database reports

Database Sub-Committee

Manufacturing Registry Sub-CommitteeSeptember 30, 2009

Chair: Sally Schwarz, MS, RPh, BCNP Charge:

– Generation I (2009) – includes Europe• Define detailed input required for manufacturers database• Provide guidance to manufacturer's related to different pathways available

for IND participation• Collect data from at least 100 sites• Demonstrate ability to generate "pick-list" reports for a drug trial sponsor

– Generation II (2010) – expand to Asia• Maintain the current database (and grow)• Generate recommendations from the manufacturer's community to the SNM

related to future potential NDAs and future access and license fees.

Manufacturing Registry Sub-Committee

Accomplishments:1. Development of manufacturers registry

– 202 sites registered– 134 U.S.– 48 Europe– 20 Other

2. Promotion of integrated manufacturing group3. Provided ongoing education through Webinars and

Annual and Midwinter meetings

Manufacturing Registry Sub-Committee

2010 Goals: Generation II

1. Work with the Database Subcommittee to launch the second phase of the database allowing more detailed manufacturing input for registered sites

2. Lead educational process for CMP part 212 regulation3. Foster working relationships between manufacturers4. Develop GMP audit program for participating

manufacturing sites5. Expand manufacturing sites in Asia6. Get Pharma involved in the next IND choice

Manufacturing Registry Sub-Committee

CTN Strategic Planning Committee

Wendy HayesSusan GalbraithLinda VelasquezOncology Discovery Medicine & Clinical BiomarkersBristol-Myers Squibb

Chicago, 30 September 2009

Network IND

• Network IND – tracer/countries• Streamlined?• Is there a process presently in place?• Specifics – once identified – what happens/steps• Status – BMS updated on regular basis (website?)• Once approved – are guidelines available to help sites

(cross reference), health authorities (all countries), etc.• Feedback loop - process for addressing issues

– FAQ, Lessons learned

Registry of Qualified Imaging Sites

• Key – acceptance by Imaging Core Labs/Academic Centers/Scientific community

• Future Phase III trials (community based practice/academic centers)• SNM – site list available for ‘public’

• Align with Netherlands (VUMC)?• What is the qualification process?

• Phantoms? • All therapeutic areas (NS, CV)

• Length of qualification – maintenance/ongoing QC• Documentation – access by core labs

• Process for sharing – BMS – gatekeeper?• Formal request process?

• Collaboration with BMS preferred providers for acceptance of qualification –open to discussion?

Access to Phantom Program

• SNM Vision?

Registry of Manufacturers

• Access to new tracer development• How will the registry of manufacturers work?

• Qualification• List of available tracers• Areas of interest for future collaboration (NS, Immunology)

Access to SNM Standardized Protocols

• Status of development• Alignment with other efforts/consortia

• CTSA?• QIBA?• ADNI?• Academia?

• Assess once finalized – website?• Feedback loop

Study Specific Protocol and Review

• SNM Vision?

Additional Issues

• Tracer shortages – FDA/Health Authority Guidelines

• Response Criteria – new tracers/FLT-PET• Network of Phase I units/Imaging Centers – NS

– Sites, tracers, patient population, regulatory timelines, throughput

• Late phase – plans for nonacademic centers

Isotope Shortage Update

Survey completed with help from the National Association of Nuclear Pharmacies

(NANP)

Two Main Generators Currently Non-functioning

• National Research Universal (NRU) Reactor in Chalk River Canada,

• High Flux Reactor (HFR), in Petten, The Netherlands.

Survey completed with help from the National Association of Nuclear Pharmacies

(NANP)

Isotope Shortage

• 59.77% pharmacies affected by molybdenum-99 shortage• Only 29.31% have access to an alternate source of

99Mo/99mTc generators• Percentage of 99mTc radiopharmaceuticals able to be

filled:– 0-25%: 6.32% – 26-50%: 14.37% – 52-75%: 20.69% – 76-100%: 18.97%

Isotope Shortage Survey Final Results

August 10, 2009

Survey completed with help from the National Association of Nuclear Pharmacies (NANP)

Changes Made in Response to Shortage

• Reschedule of patient orders to another day or time 76.29% • Cancellation of orders: 64.95% • Change in radiopharmaceutical used: 82.47% • Decrease in dosage: 81.44% • Cancelled backup doses: 71.13% • No bulk orders: 81.44% • Changed delivery schedules: 71.13% • Eliminated standing order: 68.04% • Shifted dosing times: 58.76% • Eluting older generators more often: 84.54% • Modified preparation: 34.02% • Sent doses with later calibration times: 21.65% • Delay and divide deliveries: 65.98% • Eliminate all contingency doses: 63.92%

Isotope Shortage Survey Final Results

August 10, 2009

Survey completed with help from the National Association of Nuclear Pharmacies (NANP)

Alternate Radiopharmaceuticals Used:• TI-201 instead of Tc-99m agents for cardiac imaging:

82.47% • In-111 Oxine: 5.15% • FDG for bone imaging: 6.19% • Ga-67: 2.06% • N-13 ammonia: 1.03% • F-18 NaF: 9.28% • Other: 5.15%

Isotope Shortage Survey Final Results

August 10, 2009

Survey completed with help from the National Association of Nuclear Pharmacies (NANP)

Tracer Grid

TargetMolecular Process

Imaged/Mechanism

PET

IsotopeAgent Availability

# of Single

Site INDs

Pharm/Tox,

Dosimetry

and CMC

Status

Current Clinical

Trials (single

site? Under what

auspices?)

Reference Site /

PersonComment

HypoxiaInadequate blood

supply/oxygen to tumorF-18 F-MISO Investigational NCI-CIP IND published

Investigational

Clinical Trials

ACRIN

HypoxiaInadequate blood

supply/oxygen to tumorCu-64

Cu-64-

ATSMInvestigational yes yes

HypoxiaInadequate blood

supply/oxygen to tumorF-18 FAZA Investigational yes (at least 1)

Investigational

Clinical Trials/INDSandy McEwan

HypoxiaInadequate blood

supply/oxygen to tumorF-18 F-18 EF-5 Investigational yes (at least 1)

NCI/some (not

public?)In a Phase II trial

Varian

Biosynergy; U of

Penn & maybe

Duke

F2

Nucleophilic

Chemistry;

Limited

sources who

can produce.

Hypoxia: A major factor limiting the effectiveness of chemotherapy and radiotherapy in cancer treatment

F-18 misonidazole (F-18 MISO): A molecular imaging agent indicating the sensitivity of hypoxic tumors to the cytotoxic effects of ionizing

radiation.

Cu-64 copper(II)bis(thiosemicarbazone) (Cu-64 ATSM): A molecular imaging agent preferentially taken up by hypoxic cells. The retention

of this agent is inversely proportional to tissue oxygenation allowing quantification of tumor hypoxia with PET/CT

F18 fluoroazomycinarabinofuranoside (F-18 FAZA): A molecular imaging agent for the evaluation of tumor hypoxia and radiosensitivity

with PET/CT

F-18 etanidazole (F18 EF5): A molecular imaging agent for the evaluation of tumor hypoxia with PET/CT

28Sep09

SNM Clinical Trials NetworkDraft 3 Year Plan

1. Drive understanding of the importance and need for standardization and quantitation.

2. Create a community of trained, qualified, experienced Physicians, Scientists, and certified Molecular Imaging Research Technologists.

3. Deliver high quality programs & services. When necessary, sacrifice quantity for quality. Do less (perhaps) but do it well.

2010 Top 3

Critical-to-Success Factors

Goal Breakdown

Optimal Goal: Qualify (using phantom) and validate 25+ “preferred” sites worldwide over next 12-18 months

Action Plan:• Streamline phantom and validation programs• Identify Pharma “wish list” of targeted sites

• Target imaging sites based on location and capabilities• Develop brain and cardiac phantoms

Site Qualification and Validation

Goal: Consider submission of a multicenter IND every 12-18 months based on need and feasibility

Action Plan:• Identify next tracer according to industry demand• Complete regulatory filing• Make access to multicenter IND available to network

participants

IND Development

Goal: Develop Standardized Molecular Imaging Protocols

Action Plan:• Complete standardized FDG protocol• Refine template for standardized protocols• Continue to work towards development of additional

standardization at imaging sites• Develop additional FLT protocols• Continue to develop and submit one new tracer IND per

year

Standardized Protocols

Goal: Develop Network Workshops and Courses to Promote Standardization at Imaging Sites

Action Plan:• Develop and launch courses on standardization at imaging

sites• Promote clinical research education for physicians• Offer joint sessions at national meetings (CMOD, WMIC,

annual SNM categorical)• Consider offerings at other radiological and non-radiology

conferences (RSNA, ASCO, etc)

Training and Site Orientation

Goal: Promote Clinical Research Education for Molecular Imaging Technologists

Action Plan:• Develop and implement courses for Molecular Imaging

Research Technologists (MIRT) to include:– Standardization of imaging protocols– QA/QC at imaging research sites– Importance of SOPs in Research

• Develop certification program for MIRT

Training and Site Orientation

Goal: Develop integrated database to fulfill needs of the Network

Action Plan:• Launch multi-level database to include:

– Clinical research imaging site registry– Radiopharmaceutical manufacturer registry– Site validation and qualification results– Query mechanisms for benchmarking and outcomes– “Event-driven” audits and recertifying sites

Database

Goal: Communicate Need for Clinical Research Standardization at Imaging Sites

Action Plan:• Promote courses through regional SNM chapter meetings• Develop Network Newsletter• Publish “Critical Success” white papers

• Improve adaptation and integration with bio-imaging CROs• Update CTN website to include “members-only” access to

protocol templates, FAQs, education and site-to-site communications

Communication

Goal: Communicate Need for Clinical Research Standardization at Imaging Sites Internationally

Action Plan:• Expand site qualification and validation programs

internationally• Incorporate international markets into the Network• Expand course offerings• Course offerings at international meetings (EANM, etc.)• Promote increased international Network participation

Globalization Strategy

1. Drive understanding of the importance and need for standardization and quantitation.

2. Create a community of trained, qualified, experienced and certified Molecular Imaging Research Technologists.

3. Deliver high quality programs & services. When necessary, sacrifice quantity for quality. Do less (perhaps) but do it well.

2010 Top 3

Critical-to-Success Factors

Trial Design Committee

Chair: Anthony Shields, MD, Ph.D.

Purpose:Standardization of molecular imaging protocols and

development of centralized INDs.Assist in the development of clinical trials using imaging to:

1- Develop new therapeutic agents.2- Test and validate new imaging approaches.

Trial Design Committee

Accomplishments:• FDA approved FLT biomarker IND available for cross-

reference in pharmaceutical clinical trials• Standardized imaging protocols being developed

Trial Design Committee

Goals:1. Standardized imaging protocols including FDG2. Regulatory approval of additional biomarker INDs 3. Protocol development support for pharmaceutical trials

Trial Design Committee

Targets and Marketing of Network

The Network aims to target:• Radiopharmaceutical imaging sites• Physicians and Scientists participating (or desiring to

participate) in imaging trials• Molecular Imaging Research Technologists• Tracer manufacturers• Pharmaceutical companies performing imaging trials• Collaboration with CROs• Oncologists / clinical colleagues• Other imaging societies

Target Audience

Marketing Strategy

Strategy:• Maximize Network exposure through CTN and SNM

websites• Print advertisements in JNM and newsletters• Develop and offer courses in the conduct of clinical trials

at imaging sites through:– Webinars– Live presentations– Self-taught online courses

Communication

Strategy• Increase Network awareness through presence at

national and international meetings to include:

– SNM Annual categorical– SNM Mid-winter Meeting– Joint sessions with industry leaders (CMOD, WMIC, etc.)– EANM– SNM local Chapter meetings– Non-radiology conferences (ASCO)

Communication

Strategy• Utilize Network resources to publish white papers,

articles, and editorials on:

– Need for standardization at trial sites– Phantom qualification program– Site validation program– Conduct of clinical trials at imaging sites

Communication

Strategy:Pair with pharmaceutical companies to conduct trials

utilizing tracers which will incorporate:

• Standardized imaging protocols• Phantom qualification of sites• Ongoing site quality assurance

Clinical Trials

Discussion:

• How do we market to other pharma/bio companies?• How do we market to CROs? Offer non-imaging CROs help with what they don’t

want to do Write imaging protocols/guidelines Update them on our progress and available services Imaging CROs become “preferred” groups

recommended as “go to” for Pharma

Marketing Strategy