day 1 - thursday - 1015 am - dan sullivan

8/9/2019 Day 1 - Thursday - 1015 AM - Dan Sullivan

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Daniel C. Sullivan, MD

Application of High Resolution CT Imaging Data toLung Cancer Drug Development: Measuring Progress

Progress Toward Quantitative Imaging

May 13-14, 2010Bethesda, MD


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RSNA Interests

RSNA is interested in fosteringmore emphasis on quantitativeimaging in clinical care

Facilitating imaging as abiomarker in clinical trials helpsRSNA move this agenda forward.


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Science involvesMeasurements

Lee Hartwell, PhDNobel Prize in Physiology orNobel Prize in Physiology or

Medicine, 2001Medicine, 2001President and Director, FredPresident and Director, Fred

Hutchinson Cancer ResearchHutchinson Cancer ResearchCenter, SeattleCenter, Seattle


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2009 Take-home Messages

Images are inherently quantitative: They aren-dimensional datasets

We must improve our image acquisition

parameters so that pixel/voxel values reflectthe biological parameter(s) of interest.

We must optimize image processingalgorithms to extract the pixels or voxels thatare relevant to our clinical question(s).


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2009 Challenges

In what clinical settings are quantitativeimaging results important?

How do we educate/communicatethose to radiologists?

How do we influence market demandand ROI for these capabilities?


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Progress?

Status of QIBA and related activities

Collecting evidence; making the case

Educating/communicating


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QIBA Background

Began May, 2008

Mission: Improve value and practicalityof quantitative imaging biomarkers byreducing variability across devices,patients, and time.

Build measuring devices rather thanimaging devices.


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Factors Affecting QIBA Scope

NIST definition of a measurement result: Ameasurement result is complete only whenaccompanied by a quantitative statement of

its uncertainty. The uncertainty is required inorder to decide if the result is adequate forits intended purpose and to ascertain if it isconsistent with other similar results.

FDA: A biomarker must be qualified for itsintended purpose


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QIBA Committee Leadership

CT Quantitative CommitteeAndrew Buckler, MS, Chair (Buckler Biomedical LLC)P. David Mozley, MD, Co-Chair (Merck)Lawrence Schwartz, MD, Co-Chair (Memorial Sloan-KetteringCancer 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 CommitteeGudrun 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)

CT Quantitative CommitteeAndrew Buckler, MS, Chair (Buckler Biomedical LLC)P. David Mozley, MD, Co-Chair (Merck)Lawrence Schwartz, MD, Co-Chair (Memorial Sloan-KetteringCancer 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 CommitteeGudrun 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)

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 ofWashington)

David Clunie, MBBS, Subcommittee Co-Chair(RadPharm)

Jeffrey Yap, PhD, Quality Control Metrics andCovariates Rationale Technical Subcommittee Chair

(Dana Farber Cancer Institute)

Timothy Turkington, PhD, ROI Definitions TechnicalSubcommittee Chair (Duke University Medical Center)

Ling X. Shao, PhD, Software Tracking TechnicalSubcommittee Chair (Philips Healthcare)

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 ofWashington)

David Clunie, MBBS, Subcommittee Co-Chair(RadPharm)

Jeffrey Yap, PhD, Quality Control Metrics andCovariates Rationale Technical Subcommittee Chair

(Dana Farber Cancer Institute)

Timothy Turkington, PhD, ROI Definitions TechnicalSubcommittee Chair (Duke University Medical Center)Ling X. Shao, PhD, Software Tracking TechnicalSubcommittee Chair (Philips Healthcare)

COPD/Asthma CommitteePhil Judy, PhD, Chair (Brigham & Womens)David Lynch, MD, Co-Chair (National Jewish)

COPD/Asthma CommitteePhil Judy, PhD, Chair (Brigham & Womens)David Lynch, MD, Co-Chair (National Jewish)

Steering CommitteeDan Sullivan, MD, Co-Chair (Duke; RSNA)Andy Buckler, MS, Co-Chair (Buckler Biomedical LLC)Kevin ODonnell, PhD, Co-Chair (Toshiba)

Steering CommitteeDan Sullivan, MD, Co-Chair (Duke; RSNA)Andy Buckler, MS, Co-Chair (Buckler Biomedical LLC)Kevin ODonnell, PhD, Co-Chair (Toshiba)

fMRI CommitteeCathy Elsinger, PhD, Co-Chair (Nordic Neurolab, Inc)Jeffrey Petrella, MD, Co-Chair (Duke)

Joy Hirsch, PhD, Co-Chair (Columbia)

fMRI CommitteeCathy Elsinger, PhD, Co-Chair (Nordic Neurolab, Inc)Jeffrey Petrella, MD, Co-Chair (Duke)

Joy Hirsch, PhD, Co-Chair (Columbia)


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QIBA Process

Identify sources of variability

Collect groundwork data

Devise mitigation strategies Write and promulgate Profiles.

Important progress step: NISTinvolvement to assist with developing acompliance process.


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CTSA Imaging Working Group

3 Subcommittees:

Cores (Structure; Administration;Financing)

Imaging Informatics (Integrate existingtools)

Clinical Trials (UPICT UniformProtocols for Imaging in Clinical Trials)


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Image Sharing Network Pilot Project

RSNA plus 5 medical centers

2-year, $4.7 million contract from NIBIB

American Recovery and Reinvestment Actfunds from 2009

Patient control of medical history andimaging examinations through individual

accounts in personal health recordsystems

Web-based system


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UPICT TemplateExecutive Summary

Context of the Imaging Protocol within the Clinical TrialSite Selection, Qualification and TrainingSubject SchedulingSubject PreparationImaging-related Substance Preparation and AdministrationIndividual Subject Imaging-related Quality ControlImaging ProcedureImage Post-processingImage AnalysisImage InterpretationArchival and Distribution of Data

Quality ControlImaging-associated Risks and Risk ManagementAPPENDICES


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Imaging Biomarkers

Roundtable

FNIH


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Generic Roadmap


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Imaging Biomarker RoundtableAd Hoc Committees

1. Open Image Archives

Richard Avila

Gudrun Zahlmann

1. Publication Guidelines

Paul Kinahan


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FDA Approval Vs. Qualification

Approval(or Clearance) is acknowledgementthat, for the stated claim, the drug or devicehas been shown to have acceptable safety

and effectiveness.Qualification is acknowledgement that, within a

stated context of use, the measurement canbe relied upon to have a specific

interpretation in drug development andregulatory decision-making.


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Quantitative

Imaging Test Drugor DeviceApproval[National

regulatoryagencies, e.g., FDA

CDRH or CDER]

Evidentiary Studies forCoverage Decisions

[Payer organizations,e.g., CMS]

QuantitativeImaging Test Result

Qualification[National

regulatoryagencies, e.g., FDA

CDER]

Clinic

al

TrialData

Quantitative Imaging TestDiscovery/Development/Technical

Performance[Private & Academic Sectors]

Use in RoutineClinical Care

Use in ClinicalResearch

d i i k Q lifi i


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2) Biomarker Sponsor submits to BQC a written

request for qualification of an exploratory biomarker.

3) BQC evaluates qualification request.

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 preparesfor the Biomarker Qualification face-to-face meeting.

8) BQRT and Sponsor BQDS Meeting.

9) BQRT identifies and requests additional data from

sponsor.

Proposed Imaging Biomarker Qualification Process

1) Informal discussion of a potential biomarker sponsor

with the Biomarker Qualification Coordinator (BQC).

4) Biomarker Qualification Management Team

(BQMT) accepts or declines the sponsors request to

proceed with qualification process.

CON

SULTATI O

NANDADVICEPR

OCESS

10) BQRT receives full data package and review period

begins

11) BQRT writes draft biomarker qualification review.

12) BQC routes the draft biomarker qualificationreviews to all Offices

13) BQ Project Manager schedules the BQ review for

presentation at a CDER Regulatory Briefing.

REVIEW

PRO

CESS

14) CDER Regulatory Briefing presentation and

discussion is held.

15) CDER Office Directors make decisions to accept or

reject the BQRT recommendations.

16) BQC drafts letter for sign-off by the Director of

CDER communicating to the sponsor the results of thebiomarker qualification.

Request

Letter

Briefing

Documen

t

Full Data

Package

Signoff

Letter

A) Declaratory information about the class of tests

drawn from test validation sources.

B) Phantom and other controlled condition support

material for stand-alone assessment and required

initial and ongoing quality control specifics.

E) Clinical Performance Groundwork to characterize

sensitivity and specificity for readers using the

imaging test when interpreted as a biomarker under

limited conditions.

D) Process map detailing steps contemplated to

support qualification of the biomarker

C) Implement and refine protocols for the intended

use

H) Promote use of the imaging biomarker through

education.

Sponsoring Collaborative National Regulatory Agencies

F) Clinical Efficacy Groundwork to qualify biomarker

as a surrogate endpoint in "real world" imaging

conditionsG) Draft advice guidance on incorporation of imaging

biomarker into clinical trials.


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Progress?

Status of QIBA and related activities

Collecting evidence; making the case

Educating/communicating


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NIBIB/RSNA Workshop on

Comparative Effectiveness Research (CER)

for Diagnostic Imaging

April, 2010

Challenges:

CER traditionally is focused on Outcome

The benefit of one test over another isusually small: ergo, large trials.


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CER Recommendations Enhance the collection of clinical data on

diagnostic tests to facilitate retrospectivestudies. Important items to include in electronicdatabases: reasons for ordering the test, technical characteristics of test,

test interpretation findings and reports instandardized format

post test decisions about course of care patient outcomes

The study of the impact of tests onsubsequent care and on patient outcomesneeds to become a major part of the researchagenda of diagnostic imaging.

April 2010 Constantine Gatsonis, PhD


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Educating/Communicating

Quantitative imaging content inscientific and educational componentsof RSNA Annual Meeting

Quantitative Imaging Reading Roomdisplays of available tools (imageprocessing algorithms, and structured

reporting products).


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Integrating the Imaging BiomarkerEnterprise

Public Data

Infrastructu

re

QIBADefine Profiles and

ConductGroundwork

BiopharmaPrescribe in

ClinicalTrials

Developers /VendorsValidate

Performance

UPICTManageProtocol

s

Consensu

s

Protocols

510(k)

s

Qualificatio

n Data

Profiles

NDAs

Predicate

Users and PurchasersSpecify in Tenders and

Utilize

day 1 - thursday - 1015 am - dan sullivan

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