What Can We Learn From Each Other?

Transcription

1 Imaging for Treatment Assessment in Radiation Therapy (ITART) The first biennial meeting to focus on quantitative imaging in radiation therapy. What Can We Learn From Each Other? June 21-22, 22, 2010 Washington, DC Daniel C. Sullivan, MD Duke University Medical Center RSNA Accuracy of quantitative imaging biomarker data: Requires collaboration from Physicists; Engineers; Image Processing Scientists Manufacturers Regulators Biologists/Chemists Physicians Biostatisticians; Methodologists Patient Advocates Acknowledgement Some of my following comments are influenced by: Coller, B. Translational Research: Forging a New Cultural Identity. MOUNT SINAI JOURNAL OF MEDICINE 75: , 2008 All generalizations are dangerous, even this one.» Alexandre Dumas

2 Basic Science Academicians Motivation: Discovery of new knowledge Eliminate uncertainty Avoid coming to conclusions too rapidly; Replicate results Be skeptical; challenge Incentives/Rewards: Grants/contracts Publications Independent work; Competition Promotions Physicians Motivation: Apply knowledge to improve patients health (Diagnose and Cure) Accept uncertainty Adhere to accepted methods; Conservative Accept high noise levels in clinical studies Generalize broadly from small n Rewards/Incentives: Altruistic goals (helping people) Salary (Salary offset) Status/prestige/promotions Industry Motivation: Deliver products (or services) Approach is task and goal oriented, as contrasted with the less structured academic approach R&D cost Pharmaceutical industry very high Imaging device industry moderately high Time-to-market Pharmaceutical industry 8 to 20 years Imaging device industry months to few years IP protection Pharmaceutical industry 10 to 15 years Imaging device industry 2 to 4 years Rewards/Incentives Team rewards for accomplishing goals, deliverables and product launch Profits Regulators Motivation: Fulfill legally mandated mission Mitigate harm Make binary or categorical decisions in the absence of complete data. Maintain consistent interpretations of ambiguous concepts. Rewards/Incentives: Altruistic goals Minimize erroneous decisions

3 Patients Motivation: Health Accurate diagnoses and treatment decisions Minimal cost and morbidity Rewards/Incentives Ability to Live, Work and Love Essentials for Collaboration Climate of trust An outcome that is valued by and brings value to each group Shared ownership of the final product or service. A conviction that we need each other to be successful. RSNA Strategic Plan Goal 1: Shape and advance the future of radiology. 1.3 Prepare professionals in radiologic sciences for an increasingly quantitative future. Quantitative Imaging Initiatives Quantitative Imaging Biomarkers Alliance (QIBA) Imaging Biomarkers Roundtable CTSA Imaging Working Group Uniform Protocols for Imaging in Clinical Trials (UPICT) Toward Quantitative Imaging (TQI) Quantitative Imaging Reading Room at RSNA Annual Mtg.

4 QIBA Background Began May, 2008 Mission: Improve value and practicality of quantitative imaging biomarkers by reducing variability across devices, patients, and time. Build measuring devices rather than imaging devices. A QIBA Profile is a document with 3 parts Part 1 tells a user what can be accomplished by following the Profile. (Claims) E.g. you will be able to detect volume changes of greater than 10% in Stage I lung cancer nodules which are 5mm in diameter or greater. QIBA Profile (2) Part 2 tells a vendor what they must implement in their product to state compliance with the Profile. (Details) E.g. to comply, the scanner must be able to:» scan a Mark-324 Chest Phantom, identify the smallest resolvable target, display the diameter of that target» demonstrate resolving targets at least as small as 2mm diameter on the Mark-324 phantom» scan patients according to the ACRIN NLST acquisition protocol E.g. to comply, the quantification application must be able to:» segment a nodule (automatically or manually), derive the volume, store it in a DICOM object» run a user through a set of test data with known volumes and at the end display an accuracy score QIBA Profile (3) Part 3 tells the user staff what they must do for the Profile Claims to be realized. (Details) E.g. to comply, the site CT techs must be able to:» scan the patient within 10 minutes of contrast injection E.g. to comply, the radiologist must be able to:» achieve a score of 95% or better using their segmentation application on the LIDC test set.

5 QIBA Committee Leadership How we will succeed Steering Committee Dan Sullivan, MD, Co-Chair (Duke; RSNA) Andy Buckler, MS, Co-Chair (Buckler Biomedical LLC) Kevin O Donnell, PhD, Co-Chair (Toshiba) PET/CT Quantitative Committee Richard Frank, MD, PhD, Chair (GE Healthcare) Richard Wahl, MD PhD, Co-Chair (Johns Hopkins) Paul Kinahan, PhD, Co-Chair (University of Washington) David Clunie, MBBS, Subcommittee Co-Chair (RadPharm) Jeffrey Yap, PhD, Quality Control Metrics and Covariates Rationale Technical Subcommittee Chair (Dana Farber Cancer Institute) Timothy Turkington, PhD, ROI Definitions Technical Subcommittee Chair (Duke University Medical Center) Ling X. Shao, PhD, Software Tracking Technical Subcommittee Chair (Philips Healthcare) COPD/Asthma Committee Phil Judy, PhD, Chair (Brigham & Women s) David Lynch, MD, Co-Chair (National Jewish) CT Quantitative Committee Andrew Buckler, MS, Chair (Buckler Biomedical LLC) P. David Mozley, MD, Co-Chair (Merck) Lawrence Schwartz, MD, Co-Chair (Memorial Sloan-Kettering Cancer Center) Nicholas Petrick, PhD, Group 1A Subcommittee Chair (FDA) Michael McNitt-Gray, PhD, Group 1B Subcommittee Chair (UCLA) Charles Fenimore, PhD, Group 1C Subcommittee Chair (National Institute of Standards and Technology (NIST) Anthony Reeves, PhD, Volcano (Cornell University) MRI Quantitative Committee Gudrun Zahlmann, PhD, Chair (Roche) Sandeep Gupta PhD, Co-Chair (GEHC) Ed Jackson, PhD, Co-Chair (MD Anderson Cancer Center) Mark Rosen, MD, PhD, Clinical Test-Retest Subcommittee (UPenn) Daniel Barboriak, MD, Data Simulation (Synthetic Data) Subcommittee (Duke University Medical Center) fmri Committee Cathy Elsinger, PhD, Co-Chair (Nordic Neurolab, Inc) Jeffrey Petrella, MD, Co-Chair (Duke) Joy Hirsch, PhD, Co-Chair (Columbia) With basic scientists: Facilitate funding and structured approach for assessment of accuracy and precision. With physicians: Include treating physicians in developing Profile Claims. Provide standards for evaluating imaging biomarkers in clinical trials. Facilitate validated biomarkers for use in clinical care. With industry: How we will succeed with industry Result: Widely Available, High Performance, Quantitative Imaging Imaging Science, Metrology, and Biostatistics Make it actionable for engineering and R&D, addressing both design and use QIBA PROFILE I. CLINICAL CONTEXT II. CLAIMS III. PROFILE DETAILS IV. COMPLIANCE SECTION V. ACKNOWLEDGEMENTS Participation and visibility PRODUCT CREATION PROCESS (PCP) Customer Requirements Specification (CRS) System Requirements Specification (SRS) Verification Plan and Protocol May 2010 Buckler Biomedical LLC 19 May 2010 Buckler Biomedical LLC 20

6 Make it familiar to marketing and give them a product, not just a cost FDA Approval Vs. FDA Qualification Familiar models: Familiar process: Q IBA Approval (or Clearance) is acknowledgement that, for the stated claim, the drug or device has been shown to have acceptable safety and effectiveness. Qualification is acknowledgement that, within a stated context of use, the measurement can be relied upon to have a specific interpretation in drug development and regulatory decision-making. May 2010 Buckler Biomedical LLC 21 Quantitative Imaging Test Discovery/Development/Technical Performance [Private & Academic Sectors] How will we succeed with regulators? Quantitative Imaging Test Drug or Device Approval [National regulatory agencies, e.g., FDA CDRH or CDER] Evidentiary Studies for Coverage Decisions [Payer organizations, e.g., CMS] Clinica l Trial Data Quantitative Imaging Test Result Qualification [National regulatory agencies, e.g., FDA CDER] Provide standards Adopt/adapt their paradigms Aggregate data and perform metaanalyses Use in Routine Clinical Care Use in Drug Development

7 2) Biomarker Sponsor submits to BQC a written Proposed Imaging Biomarker Qualification Process Sponsoring Collaborative National Regulatory Agencies A) Declaratory information about the class of Request 1) Informal discussion of a potential biomarker sponsor tests drawn from test validation sources. Letter with the Biomarker Qualification Coordinator (BQC). B) Phantom and other controlled condition support material for stand-alone assessment and required initial and ongoing quality control specifics. C) Implement and refine protocols for the intended use D) Process map detailing steps contemplated to support qualification of the biomarker E) Clinical Performance Groundwork to characterize sensitivity and specificity for readers using the imaging test when interpreted as a biomarker under limited conditions. F) Clinical Efficacy Groundwork to qualify biomarker as a surrogate endpoint in "real world" imaging conditions G) Draft advice guidance on incorporation of imaging biomarker into clinical trials. Briefing Document Full Data Package request for qualification of an exploratory biomarker. 3) BQC evaluates qualification request. 4) Biomarker Qualification Management Team (BQMT) accepts or declines the sponsor s request to proceed with qualification process. 5) Biomarker Qualification Review Team (BQRT) requests briefing document from biomarker sponsor. 6) BQ Project Manger schedules face-to-face meeting between the sponsor and the BQRT. 7) BQRT evaluates the briefing document and prepares for the Biomarker Qualification face-to-face meeting. 8) BQRT and Sponsor BQDS Meeting. 9) BQRT identifies and requests additional data from sponsor. 10) BQRT receives full data package and review period begins 11) BQRT writes draft biomarker qualification review. CONSULTATION AND ADVICE PROCESS FNIH Imaging Biomarkers Roundtable Your Logo Here 12) BQC routes the draft biomarker qualification reviews to all Offices 13) BQ Project Manager schedules the BQ review for presentation at a CDER Regulatory Briefing. 14) CDER Regulatory Briefing presentation and discussion is held. 15) CDER Office Directors make decisions to accept or reject the BQRT recommendations. REVIEW PROCESS H) Promote use of the imaging biomarker through education. Signoff Letter 16) BQC drafts letter for sign-off by the Director of CDER communicating to the sponsor the results of the biomarker qualification. UPICT Template Headings UPICT Imaging Protocol Template Executive Summary Context of the Imaging Protocol within the Clinical Trial Site Selection, Qualification and Training Subject Scheduling Subject Preparation Imaging-related Substance Preparation and Administration Individual Subject Imaging-related Quality Control Imaging Procedure Image Post-processing Image Analysis Image Interpretation Archival and Distribution of Data Quality Control Imaging-associated Risks and Risk Management APPENDICES UPICT Template UPICT Template Imaging Protocol Executive Summary Context of the Imaging Protocol within the Clinical Trial Site Selection, Qualification and Training Subject Scheduling Subject Preparation Imaging-related Substance Preparation and Administration Individual Subject Imaging-related Quality Control Imaging Procedure Image Post-processing Image Analysis Image Interpretation Archival and Distribution of Data Quality Control Imaging-associated Risks and Risk Management APPENDICES

8 Summary What can we learn from each other? Understand each other s needs (what key missing component will help accomplish their job?) Satisfy each other s motivations/agendas Help each other achieve their rewards/incentives