2009 Strategic Planning Meeting SNM Clinical Trials Network Chicago, IL

Transcription

1 2009 Strategic Planning Meeting SNM Clinical Trials Network Chicago, IL Wednesday, September 30, 2009 AGENDA Item BREAKFAST Welcome and Introductions Time 8:00am 8:15 Discussion Leaders 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

2 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

3 2009 Summary of Progress

4 Key Accomplishments 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

5 Major Goals 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

6 Phantom Sub-Committee

7 Phantom Sub-Committee Chair: Paul Christian, CNMT, BS, PET Purpose: Management of phantom program for site qualification Clinical Simulation Phantoms Evaluate: Image performance -Acquisition -Processing -Interpretation Lesion detection SUV measurements Purpose of PET phantom -Uniformity -Resolution -Contrast -Noise -Quantitative accuracy -PET/CT alignment -Attenuation correction

8 Accomplishments: 1. Development of phantom qualification process 2. Phantom acquisition Phantom Sub-Committee 3. Phantom review and quality assurance testing 4. Administration of FLT, chest phantom demonstration project

9 Submit Images and SUV Data

10 SUVmax SUVmax SUVmax Site Phantom Qualification Assess: 3.5 Acquisition protocol 3 Accuracy of dose Reconstruction/filter 2.5 Image quality 2 PET/CT alignment Attenuation 1.5 correction1.5 Image noise 1 Image contrast MD 0.5 visual assessment 0.5 Lesion detectability SUV accuracy DICOM transfer valid Validation of SUV DICOM PET Qualification Chest Phantom PET Qualification PET Qualification Chest Phantom Chest Phantom Lesion Number Lesion Number Lesion Number Series1 Series2 Series3 Series4 Series5 Series6 Series7 Series1 Series2 Series3 Series4 Series5 Series6 Series7 Series1 Series2 Series3 Series4 Series5 Series6 Series7

11 2010 Goals: 1. Streamline phantom qualification program Phantom Sub-Committee 2. Develop process for long term maintenance and administration of phantom site qualification 3. Develop additional phantom programs including brain and cardiac

12 Site Validation and Monitoring Committee

13 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

14 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

15 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

16 Site Validation and Monitoring Committee

17 Education Update

18 Standardization across clinical sites Summary of Identified Needs Research related training for technologists Good Clinical Practice in Research Imaging specific

19 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

20 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

21 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

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

23 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

24 Education Update Tech Educators Sub-Committee

25 Educational Offerings 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) All courses offered online (continuous) and at SNM meetings

26 Educational Offerings 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

27 Delivery Channels 1. Online educational offerings for technologists (continual) 2. Live course presentations at meetings 3. Brochures and poster presentations at sectional meetings

28 Plans for Meetings Panel 1: Potential Role of Imaging Biomarkers in Development of Neurological Therapeutics CMOD 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

29 Plans for Meetings WMIC Introduction to the SNM Clinical Trials Network George 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

30 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

31 Database Sub-Committee

32 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

33 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

34 CTN Database Structure and Flow

35 Database Sub-Committee 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

36 Manufacturing Registry Sub-Committee September 30, 2009

37 Manufacturing Registry Sub-Committee 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.

38 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 group 3. Provided ongoing education through Webinars and Annual and Midwinter meetings

39 2010 Goals: Generation II Manufacturing Registry Sub-Committee 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 regulation 3. Foster working relationships between manufacturers 4. Develop GMP audit program for participating manufacturing sites 5. Expand manufacturing sites in Asia 6. Get Pharma involved in the next IND choice

40 CTN Strategic Planning Committee Wendy Hayes Susan Galbraith Linda Velasquez Oncology Discovery Medicine & Clinical Biomarkers Bristol-Myers Squibb Chicago, 30 September 2009

41 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

42 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?

43 SNM Vision? Access to Phantom Program

44 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)

45 Access to SNM Standardized Protocols Status of development Alignment with other efforts/consortia CTSA? QIBA? ADNI? Academia? Assess once finalized website? Feedback loop

46 SNM Vision? Study Specific Protocol and Review

47 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

48 Isotope Shortage Update Survey completed with help from the National Association of Nuclear Pharmacies (NANP)

49 Two Main Generators Currently Non-functioning Isotope Shortage 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)

50 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% %: 18.97% Isotope Shortage Survey Final Results August 10, 2009 Survey completed with help from the National Association of Nuclear Pharmacies (NANP)

51 Changes Made in Response to Shortage Isotope Shortage Survey Final Results August 10, 2009 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% Survey completed with help from the National Association of Nuclear Pharmacies (NANP)

52 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)

53 Tracer Grid Hypoxia: A major factor limiting the effectiveness of chemotherapy and radiotherapy in cancer treatment Target Molecular Process Imaged/Mechanism PET Isotope Agent Availability # of Single Site INDs Pharm/Tox, Dosimetry and CMC Status Current Clinical Trials (single site? Under what auspices?) Reference Site / Person Comment Hypoxia Hypoxia Inadequate blood supply/oxygen to tumor Inadequate blood supply/oxygen to tumor F-18 F-MISO Investigational NCI-CIP IND published Cu-64 Cu-64- ATSM Investigational yes yes Investigational Clinical Trials ACRIN Hypoxia Inadequate blood supply/oxygen to tumor F-18 FAZA Investigational yes (at least 1) Investigational Clinical Trials/IND Sandy McEwan Hypoxia Inadequate blood supply/oxygen to tumor F-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. 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

54 SNM Clinical Trials Network Draft 3 Year Plan

55 2010 Top 3 Critical-to-Success Factors 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.

56 Goal Breakdown

57 Site Qualification and Validation Optimal Goal: Qualify (using phantom) and validate 25+ preferred sites worldwide over next 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

58 IND Development Goal: Consider submission of a multicenter IND every 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

59 Standardized Protocols 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

60 Training and Site Orientation 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)

61 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

62 Goal: Develop integrated database to fulfill needs of the Network Database 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

63 Goal: Communicate Need for Clinical Research Standardization at Imaging Sites Communication 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

64 Globalization Strategy 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

65 2010 Top 3 Critical-to-Success Factors 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.

66 Trial Design Committee

67 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.

68 Accomplishments: Trial Design Committee FDA approved FLT biomarker IND available for crossreference in pharmaceutical clinical trials Standardized imaging protocols being developed

69 Trial Design Committee Goals: 1. Standardized imaging protocols including FDG 2. Regulatory approval of additional biomarker INDs 3. Protocol development support for pharmaceutical trials

70 Targets and Marketing of Network

71 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

72 Marketing Strategy

73 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

74 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

75 Strategy Communication 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

76 Strategy: Pair with pharmaceutical companies to conduct trials utilizing tracers which will incorporate: Clinical Trials Standardized imaging protocols Phantom qualification of sites Ongoing site quality assurance

77 Discussion: Marketing Strategy 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