Uniform Protocols In Clinical Trials (UPICT) Standardized FDG-PET ...

Uniform Protocols In Clinical Trials (UPICT)
Standardized FDG-PET/CT Protocol
Jeffrey T. Yap, PhD
SNM Midwinter Meeting
Orlando, FL,
January 27, 2012

• Grant Funding
– Bayer
– BristolMyersSquibb
– Pfizer
– Toshiba
• Consultant
– IBA Molecular
Disclosure
• Presentation may include
unlabeled/unapproved use of FDG

CTSA Imaging Working Group
• Initiated in 2008 to coordinate imaging efforts
across centers with Clinical Translational
Science Awards (CTSA)
• Sponsored/coordinated by RSNA
• Industry participation from pharma, imaging
CROs
• Subgroups
– Cores/Education
– Imaging informatics
– UPICT/Imaging in Clinical Trials

UPICT Goals
• Reduce variance related to imaging in the
conduct of clinical trials
– Improve the detection of differences due to study intervention
– support optimization and validation of imaging biomarkers
• Develop generic template and library of
specific protocols

UPICT History
• Bi-monthly calls and annual working
group meetings at RSNA starting in 2008
• CTSA/IRAT meeting in 2009
– Generic template
– FDG-PET oncology, vCT, Alzheimer’s PET
• FDG-PET writing group
– Weekly calls since early 2010
– Coordination with SNM global harmonization summit (June 2010)

UPICT FDG-PET writing group
Ronald Boellaard
Paul Christian
Gary Dorfman (Chair) John Sunderland
Michael Graham
Otto Hoekstra
John Hoffman
Paul Kinahan
Eric Perlman
Richard Wahl
Jeffrey Yap

SNM FDG-PET Global Harmonization (6/2010)
Ronald Boellaard
Andrew Buckler
Michael Casey
Paul Christian
Pat Cole
Dominique Delbeke
Michael Graham
Nathan Hall
John Hoffman
Michael Knopp
Karen Kurdziel
Chieko Kurihara-Saio
David Mankoff, MD
Paul Marsden
George Mills
James Mountz
Jin Chul Paeng
Eric Perlman
Lucy Pike
Andrew Scott
Lingxiong Shao
Daniel Sullivan
Richard Wahl
Wolfgang Weber
Jeffrey Yap

UPICT template headings
0. Executive Summary
1. Context of the Imaging Protocol within the
Clinical Trial
2. Site Selection, Qualification and Training
3. Subject Scheduling
4. Subject Preparation
5. Imaging-related Substance Preparation and
Administration
6. Individual Subject Imaging-related Quality
Control

UPICT template headings
8. Imaging Procedure
9. Image Post-processing
10. Image Analysis
11. Image Interpretation
12. Archival and Distribution of Data
13. Quality Control
14. Imaging-associated Risks and Risk
Management

UPICT Appendices
A. Acknowledgements and Attributions
B. Background Information
C. Conventions and Definitions
D. Documents included in the imaging protocol
(e.g., CRFs)
E. Associated Documents (derived from the
imaging protocol or supportive of the imaging
protocol)
F. Model-specific Instructions and Parameters

UPICT Framework
• Librarian/Editor function
• Collection and extraction of available
resources into UPICT template
• Consolidated and Consensus statements
• Bullseye approach to compliance
– Acceptable
– Target
– Ideal

Wikipedia of FDG-PET procedures?
• Many contributors and authors
• Citation for sources
• Bibliography, appendices
• Comprehensive, specific, detailed
– 14 page template
– 66 pages excluding references, appendices
• Will be open for public comment/revisions
• Alzheimer’s and FLT protocols underway

Accuracy ✔
Sensitivity ✔
Specificity ✔
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0. Executive Summary
“This UPICT Protocol is intended to guide the
performance of whole-body FDG-PET/CT within the
context of single- and multi-center clinical trials of
oncologic therapies by providing acceptable (minimum),
target, and ideal standards for all phases of the imaging
examination as defined by the UPICT Template (ref) with
the aim of minimizing intra- and inter-subject, intra- and
inter-platform, inter-examination, and inter-institutional
variability of primary and/or derived data that might be
attributable to factors other than the index intervention
under investigation.”

1. Context of the Imaging Protocol within the Clinical Trial
1.1. Utilities and Endpoints of the Imaging Protocol
1.2. Timing of Imaging within the Clinical Trial Calendar
1.3. Management of Pre-enrollment Imaging
1.4. Management of Protocol Imaging Performed Off-schedule
1.5. Management of Protocol Imaging Performed Offspecification
1.6. Management of Off-protocol Imaging
1.7. Subject Selection Criteria Related to Imaging
1.7.1. Relative Contraindications and Remediations
1.7.2. Absolute Contraindications and Alternatives
1.7.3. Imaging-specific Inclusion Criteria

1.7.2 Absolute Contraindications and Alternatives
Quantitative Primary imaging endpoint: “it is
suggested that diabetic subjects unable to
achieve a fasting blood glucose level (without the
use of short-acting / regular insulin within four
hours preceding the FDG-PET/CT study) of

1.7.2 Absolute Contraindications and Alternatives
Qualitative or Secondary imaging endpoint: “it is
suggested that the trial explicitly state whether
subjects unable to achieve a fasting blood
glucose level of

3. Subject Scheduling
“For known diabetic subjects with anticipated
fasting blood glucose measurements for the day
of the examination between 126 mg/dl and
200mg/dl, the following scheduling
recommendations apply:
– Ideal / Target: Type I and Type II diabetic subjects should be
scanned early in the morning before the first meal, and doses of
insulin and/or hypoglycemic medication should be withheld if
glucose levels remain in the acceptable range. This should be
established from morning blood glucose levels prior to the study.”

3. Subject Scheduling
– “Acceptable: Type I and Type II diabetic subjects, who cannot reliably attain
acceptable glucose levels early in the morning, should be scheduled for late
morning, and should eat a normal breakfast at 7 am and take their normal
morning diabetic drugs; then fast for at least 4 hours till exam. This strategy is
acceptable only for
• Non-quantitative PET/CT, or
• Endpoints that are not for the primary aim, or
• Subjects whose baseline study was performed with a FBG

5.3 Timing, Subject Activity Level, and Factors
Relevant to Initiation of Image Data Acquisition
• Consolidated statement on FDG uptake period:
“The suggested consensus time (from all references)
between FDG administration and scan acquisition
is 60 minutes based on historical use of this test;
assuming this is the target window, an acceptable
window is often cited as +/- 5 minutes (55-65
minutes). Two references (NCI and ACRIN) allow
the acceptable window to be +/- 10 minutes (50-70
minutes), which is considered the absolute
minimum of acceptability.”

5.3 Timing, Subject Activity Level, and Factors
Relevant to Initiation of Image Data Acquisition
• Consolidated statement on FDG uptake period:
“However, on the basis of the SNM harmonization
summit while the “target” tracer uptake time is
60 minutes, the “acceptable” window is from 55
to 75 minutes so as to ensure that imaging does
not begin prematurely so as to allow adequate
tumor uptake of FDG and to account for the
practicality of work flow which often does not
accommodate imaging at exactly 60 minutes
after FDG injection.”

12.1.1 Quality Control Procedures

Appendix G: Vendor/Model Specific QC

Appendix G: Vendor/Model Specific QC

Appendix G: Vendor/Model Specific QC

Resources
• http://wiki.ctsa-imaging.org