NCI case report form standardization activities in the Cancer Biomedical Informatics Grid
- 1. NCI Clinical Case Report Form (CRF) Standardization
Activities George A. Komatsoulis, Ph.D. Deputy Director Center for
Biomedical Informatics and Information Technology (CBIIT) National
Cancer Institute
2. A wonderful fact to reflect upon, that every human creature
is constituted to be that profound secret and mystery to every
other. Charles Dickens:A Tale of Two Cities 1859 3. Childhood
Cancer: Dramatic Improvement in Survival *5-year relative survival
rates, based on follow up of patients through 2003. Source:
Surveillance, Epidemiology, and End Results Program, 1975-2003,
Division of Cancer Control and Population Sciences, National Cancer
Institute, 2006. 5 - Year Relative Survival Rates * Age Year of
Diagnosis 0 - 4 Years 5- 9 Years 10- 14 Years 1975 - 1977 1996 -
2002 1975 - 1977 1996 - 2002 1975 - 1977 1996 - 2002 79.7 77.9 80.1
58.8 58.2 57.3 4. High Participation in Clinical Research
Winchester et al.,CA Cancer J Clin2001;51;119-130 5. Childhood ALL:
Molecular Sub-types Impact Risk Tsao et al.Modern
Pathology(2004)17: 832839Rubnitz and Pui,Oncologist ( 1997)2
:374-380 6. Childhood Cancer Treatment Demonstrates the New
Molecular Medicine Model
- Treatment is delivered in an environment that blends care and
research
- Researchers and practitioners are able to correlate
experimental laboratory data with clinical data (treatment,
history, pathology,outcome, etc.)
- Clinical data are utilized to continuously evaluate
outcomes
- Researchers develop and refine evidence-based strategies at an
individualized level
- Care providers improve quality by adherence to care
standards
Information flow is critical this model cannot be achieved
without the ability to reuse and aggregate data in novel ways! 7.
Improving the Return on the Nations Investment in Cancer
Research
- Human Clinical Trials are of immense importance to providing
new and improved treatments for patients, yet by their nature they
have several undesirable traits including potential harm to
patients and immense expense.
- For these and other reasons, it is absolutely essential to
maximize the return on investment (ROI) in human clinical research
either by (1) decreasing the costs associated with trials or (2)
increasing the amount of information extracted from any single
clinical trial
- Two primary mechanisms by which data sharing and data standards
can aid in ROI:
-
- Reduce the time and costs associated with setting up a clinical
trial
-
- Enhance the ability of other groups to reuse the data collected
in one clinical trial (for example, in longitudinal studies)
- In order to reuse data, it is necessary to have a thorough
understanding of its meaning
8. And the Lord said, Behold, the people is one, and they have
all one language; and this they begin to do; and now nothing will
be restrained from them, which they have imagined to do. Go to, let
us go down, and there confound their language, that they may not
understand one another's speech. Genesis , Chapter 11, 500-450 BCE
What we have here is failure to communicate Strother Martin inCool
Hand Luke1967 9. Attribute Value Agent NSCNumber 007 Name Taxol 10.
Attribute Value NCI Meaning Agent A chemical compound administered
to a human being to treat an existing disease or condition, or
prevent the onset of a disease or condition nSCNumber 007
Identifier given to a chemical compound by the US Food and Drug
Administration (FDA) Nomenclature Standards Committee (NSC) Name
Taxol Name of a chemical compound given by the NCI Cancer
Therapeutics Evaluation Program (CTEP) 11. Attribute Value NCI
Meaning CIA Meaning Agent A chemical compound administered to a
human being to treat an existing disease or condition, or prevent
the onset of a disease or condition A sworn intelligence agent; a
spy nSCNumber 007 Identifier given to a chemical compound by the US
Food and Drug Administration (FDA) Nomenclature Standards Committee
(NSC) Identifier given to an intelligence agent by the National
Security Council Name Taxol Name of a chemical compound given by
the NCI Cancer Therapeutics Evaluation Program (CTEP) Code name
given to intelligence agents by the Central Intelligence Agency
(CIA) 12. Attribute Value NCI Metadata CIA Metadata Agent A
chemical compound administered to a human being to treat an
existing disease or condition, or prevent the onset of a disease or
condition A sworn intelligence agent; a spy nSCNumber 007
Identifier given to a chemical compound by the US Food and Drug
Administration (FDA) Nomenclature Standards Committee (NSC)
Identifier given to an intelligence agent by the National Security
Council Name Taxol Name of a chemical compound given by the NCI
Cancer Therapeutics Evaluation Program (CTEP) Code name given to
intelligence agents by the Central Intelligence Agency (CIA) 13.
Empowering Data Reuse: Semantic Metadata
- Reuse therefore requires semantic metadata; information that
conveys what is being recorded and what constitutes a valid
response for that particular element.
- An international standard (ISO/IEC 11179) exists for such
semantic metadata, this standard has been leveraged to create the
cancer Data Standards Repository (caDSR).
- The basic unit of metadata in the caDSR is a Common Data
Element or CDE.
14. The ISO 11179 Model in the caDSR 15. The cancer Data
Standards Repository (caDSR) 16. Enterprise Vocabulary Service
(EVS) 17. Square Pegs and Round Holes 18. Clinical Trials Working
Group
- National Cancer Advisory Board Group
- Report Re-structuring the National Cancer Clinical Trials
Enterprise (June 2005)
- Remit: advise onwhether, andin what ways, the NCI-supported
national clinical trials enterprise should be restructured to
realize the promise of molecular medicine for advancing oncologic
clinical practice in the21stCentury
19. Clinical Trials Working Group (CTWG) CTWG Goal CTWG
Initiative Enhanced Coordination Establish a comprehensive database
containing regularly-updated information on all NCI-funded clinical
trials Enterprise Wide Standardization Achieve industry and FDA
concurrence on standard Case Report Forms incorporating Common Data
Elements Promote establishment of national clinical trial
information technology infrastructures that are fully interoperable
with NCIs cancer Biomedical Informatics Grid (caBIG) Develop a
credentialing system for investigators and sites that is recognized
and accepted by NCI, industry sponsors, clinical investigators, and
clinical trial sites 20. Characteristics of a library of
standardized CRF modules
- A library of modules, containing questions to be used in CRFs
in all oncology trials
- These modules would not be a set of required forms,per se ,
instead they contain the set of data elements that must be
collected during a trial
- These modules do not restrict investigators from collecting
additional information
21. Genius is one percent inspiration and ninety-nine percent
perspiration Thomas Alva Edison,Harpers Monthly , September 1932
22. Case Report Forms Based on Common Data Elements (CDEs) 23. CRF
Standardization Global Process
-
- Existing case report forms (whether harmonized or not)
-
- Initial inventory from forms whose metadata are captured in the
cancer Data Standards Repository (caDSR)
-
- Based on the inventory and Steering Committee feedback, select
the areas for harmonization.
- Analyze and Harmonize (Working Groups)
-
- Come to agreement on the core questions associated with a
specific CRF
-
- Reach out to the community for additional CRFs in this
area
-
- Come to agreement on the core data to be collected on this
specific CRF
-
- Important to ensure acceptance of the harmonized CRFs
-
- CRF SIG and caBIG program will provide the mechanism to receive
input
24. CRF Analysis Methodology
- Part III:Detailed Analysis
- Important caveat: We should not be creating new questions that
have not been asked on an existing CRF
25. CRF Questions:Partition Issues
-
- FDA Representatives, Compliance Officers, Regulatory Affairs
Officers
-
- NCI Division Representatives, Principal Investigators
-
- Principal Investigators, Data Managers, Biostatisticians,
Oncology Nurses and the rest of our community
- External Standards Requirements
-
- Standards Organizations (CDISC, HL7, FHA, etc.)
26. CRF Questions:Detailed Analysis
- Question by question (or CDE by CDE) analysis
- General Strategy (Proposed order of precedence)
- The same constraints apply to CDE level analysis
27. Demography: A Definition
- Pronunciation:di-'m-gr&-fE
- Etymology:Frenchdmographie,from GreekdEmospeople +
French-graphiegraphy
- Definition:The statistical study of human populations
especially with reference to size and density, distribution, and
vital statistics
28. Sources of CRFs: Demography Analysis
29. Working Group Members
- Sharon Elcombe, Mayo (Informatician)
- Rhonda Facile, CDISC (Data Standards)
- Howard Fingert, Pfizer (Clinician)
- Lara Fournier, Oregon Health Science University
(Informatician)
- Marsha Ketcham,Univ. of Nebraska Cancer Center (Clinical
Research Coordinator)
- Darlene Kiniry, NSABP (Informatician)
- George Komatsoulis, NCI Informatician
- Brenda Maeske, SAIC/CBIIT (Data Element Specialist)
- Beverly Meadows, DCP (Oncology Nurse)
- Jon Neville, Cpath (Drug Policy)
- Susan Pannoni, City of Hope ()
- Stephine Wasielewsky, Univ. of Wisconsin Cancer Center
- Dianne Reeves, CBIIT (Oncology Nurse)
- Aaron Seib, OmnicommSystems (Informatician)
- Ann Setser, CTEP (Oncology Nurse)
- Adel Taweel, Univ. of Birmingham, UK (Informatician)
- Gary Walker, Quintiles/CDASH
30. Actions to date
- Harmonized Demography Module created by Working Group
- Module reviewed within caBIG Clinical Trial Management Systems
(CTMS) workspace
- Module approved for wider review by NCI Clinical/Translational
Operating Committee (CTROC)
- Module circulated for wide review:
-
- Cancer Policy Today and other ASCO vehicles
- Comments received and analyzed
- Presented to CTROC, governing board for CTMS Working Group
activities at NCI
-
- CTROC Approved Demography Module as an NCI Standard
- Some implementation Details Still to be determined
31. CDASH and caBIG: Complementary Activities
- The CDASH initiative that is managed by the CDISC consortium
and the NCI/caBIG Case Report Form (CRF) Harmonization activity are
both concerned with harmonizing and standardizing the collection of
data in clinical trials, but their focus and granularity differ
somewhat
-
- CDASHs efforts are focused on elements that are common
toallclinical trials
-
- caBIG is focused on trials in the oncology space
- NCI/caBIG CRF modules will (at a minimum) include all CDASH
mandatory questions plus additional content that is essential in
the oncology space.
NCI mandatory CDASH mandatory 32. caBIG/CDASH Collaboration
Mechanisms
-
- NCI/caBIG is providing staff to many CDASH streams
-
- CDASH project director (Rhonda Facile) sits on the NCI Task
Force that manages the CRF project
-
- Where CDASH streams complete before NCI CRF modules are
defined, the CDASH module is one of the inputs to the NCI working
groups and vice versa
- Terminology and Metadata Support
-
- NCI Enterprise Vocabulary Services (EVS) provides terminology
support for CDISC/CDASH
-
- NCI cancer Data Standards Repository (caDSR) provides a
repository to maintain CDISC/CDASH data elements
33. , , , , : Tell me, O Muse, of the man of many devices, who
wandered full many ways after he had sacked the sacred citadel of
Troy Homer:The Odyssey (8 thCentury BCE) 34. Status: Round 1
- Round 1:Demography Module
-
- Form template with instructions are in the caDSR
- Entered Early Adopter Phase November 1, 2008
35. Status: Round 2
-
- Participant Identification
- Completed Community review September 5, 2008
- Comments reconciled by Workgroup October 3, 2008
- Presented to CTROC for review
36. Status: Round 3
-
- Staging/Extent of Disease
- Kick-off Teleconference September 4, 2008
- Groups will run approximately three to four months
37. Implementation of Subsequent Modules
- Begin successive modules every 3 to 4 months
- Observe the same schedule
-
- Reconciliation of comments
-
- Submission to CTROC for approval
-
- Early adoption to gather more pragmatic information
-
- Close early adoption and make module changes
-
- Mandate widespread use three months later
38. CRF Planning Matrix 39. Change Management and Review
- Every calendar year the total library of CRFs will be reviewed
for changes
- Older versions will be appropriately archived yet accessible as
required
- caBIG will providesupport for updates and release with version
control
- Modifications will be requested and changes will be vetted by
community and the NCI.
- All CRF Versions will be provided andMaintained on the NCI
website
- The Demography CRF module will become a candidate for review in
April 2010.
40. Thank You
-
- Joyce Niland (City of Hope)
-
- Krishnakant (Avinash) Shanbhag
- caBIG CTMS Steering Committee
- American Society for Clinical Oncology (ASCO)
the bravest are surely those who have the clearest vision of
what is before them, glory and danger alike, and yet
notwithstanding, go out to meet it. Thucydides,c.400 BCE