Historical Perspectives in CDM
Overview of the Draft Guidance
A Risked-Based Approach
Challenges to a Risk-Based Approach
Supporting a Risked-Based Approach
The FDA Guidance of a Risk-Based Approach to Monitoring as Viewed By CDM
1. The FDA Guidance of a Risk-Based Approach
to Monitoring as Viewed By CDM
William Gluck, Ph.D.
VP, Clinical and Consulting Services
8 February 2013
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16th Annual Workshop in Japan for CLINICAL DATA MANAGEMENT SMART CDM
February 7-8,2013 | Tower Hall Funabori, Tokyo, Japan
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3. Agenda
► HistoricalPerspectives in CDM
► Overview of the Draft Guidance
► A Risked-Based Approach
► Challenges to a Risk-Based Approach
► Supporting a Risked-Based Approach
► Summary
16th Annual Workshop in Japan for CLINICAL DATA MANAGEMENT SMART CDM
February 7-8,2013 | Tower Hall Funabori, Tokyo, Japan
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4. Historical Perspectives in CDM
► Drug development process
• Paper-based processing
► Electronic Data Capture
• Interactive processing
16th Annual Workshop in Japan for CLINICAL DATA MANAGEMENT SMART CDM
February 7-8,2013 | Tower Hall Funabori, Tokyo, Japan
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5. Historical Perspectives in CDM
Age of technological advances
• Application of technology
to a process: introducing
risk
• Integration of technology
as part of a risk-based
approach
16th Annual Workshop in Japan for CLINICAL DATA MANAGEMENT SMART CDM
February 7-8,2013 | Tower Hall Funabori, Tokyo, Japan
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6. FDA Draft Guidance
► Risk-Based monitoring
► 1988 guidance withdrawn
► Centralized (off-site) monitoring is
encouraged and suggested to replace on-site
monitoring when it can complete activities
better or as well as on-site
16th Annual Workshop in Japan for CLINICAL DATA MANAGEMENT SMART CDM
February 7-8,2013 | Tower Hall Funabori, Tokyo, Japan
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7. FDA Draft Guidance
► Well-defined risk-based monitoring plan
could improve the quality and integrity
of data
• Publications suggest that data anomalies
may be more readily detected
► Integrating technology appropriately to
support a risk-based approach can
enable decreased reliance on on-site
monitoring (reduced cost)
16th Annual Workshop in Japan for CLINICAL DATA MANAGEMENT SMART CDM
February 7-8,2013 | Tower Hall Funabori, Tokyo, Japan
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8. A Risk-Based Approach
► Protocol – Key Challenge
► Developing strategies/plans to implement
centralized monitoring
► Enabling the Risked-Based Approach:
Process Integration
► Supporting the Risked-Based Approach
16th Annual Workshop in Japan for CLINICAL DATA MANAGEMENT SMART CDM
February 7-8,2013 | Tower Hall Funabori, Tokyo, Japan
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9. Challenges to a Risk-Based Approach
“The most important tool for ensuring
human subject protection and high-quality
data is a well-designed and articulated
protocol.”
16th Annual Workshop in Japan for CLINICAL DATA MANAGEMENT SMART CDM
February 7-8,2013 | Tower Hall Funabori, Tokyo, Japan
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10. Challenges to a Risk-Based Approach
Guidance intends to assist in developing risk-
based monitoring strategies/planning
• Tailored to subject protection and data integrity
• Focuses on critical study parameters
• Encourages use of a combination of monitoring activities
• Encourages greater reliance on centralized monitoring
practices, where appropriate
16th Annual Workshop in Japan for CLINICAL DATA MANAGEMENT SMART CDM
February 7-8,2013 | Tower Hall Funabori, Tokyo, Japan
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11. Challenges to a Risk-Based Approach
Well-Defined Monitoring Plans:
• Description of monitoring approaches (e.g., timing,
intensity, activities, documentation) – Targeted SDV
• Communication of monitoring results
• Management of noncompliance
• Training and study-specific information
• Monitoring plan amendments
16th Annual Workshop in Japan for CLINICAL DATA MANAGEMENT SMART CDM
February 7-8,2013 | Tower Hall Funabori, Tokyo, Japan
Confidential – 11
12. Process Integration Enables the Risk-
Based Approach
Key Processes must be integrated:
• Data Collection, Cleaning, Monitoring
– eCRF design (including protocol deviations and
edit checks) require both Clinical Operations
and CDM
– Query process is interactive/optimized
between Clinical Operations and CDM
– Dynamic monitoring-Real time data sharing
between Clinical Operations and CDM
16th Annual Workshop in Japan for CLINICAL DATA MANAGEMENT SMART CDM
February 7-8,2013 | Tower Hall Funabori, Tokyo, Japan
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13. Supporting the Risked-Based Approach
CDM plays a critical role
Technologically there are few challenges
Process/Workflow Flow – KEY!
Specific strategies to reduce risk
Focus on data quality/integrity
Define and share study metrics
Enhance training and communication
16th Annual Workshop in Japan for CLINICAL DATA MANAGEMENT SMART CDM
February 7-8,2013 | Tower Hall Funabori, Tokyo, Japan
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14. Data Quality/Integrity
► Identify critical study data and processes
• Endpoints
• Serious Adverse Events
• Randomization/ Blinding
• Consent
• Eligibility Criteria
• Risks specific to protocol design and conduct
16th Annual Workshop in Japan for CLINICAL DATA MANAGEMENT SMART CDM
February 7-8,2013 | Tower Hall Funabori, Tokyo, Japan
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15. Define and Share Study Metrics
Provide performance metrics
Monitor data quality
Identify higher risk sites
Support 100%, partial, and remote SDV
Dynamic analysis of data - identify trends
Provide analysis to evaluate specific subject
data – especially outliers
16th Annual Workshop in Japan for CLINICAL DATA MANAGEMENT SMART CDM
February 7-8,2013 | Tower Hall Funabori, Tokyo, Japan
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16. Enhance Quality with Technology
Provide multiple training options:
Face-to-Face Training
Virtual Interactive Training
Multimedia e-Training
16th Annual Workshop in Japan for CLINICAL DATA MANAGEMENT SMART CDM
February 7-8,2013 | Tower Hall Funabori, Tokyo, Japan
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17. Summary
► Draft guidance acknowledges that changes
to monitoring are OK
► A risked-based approach does not eliminate
risk – there is a balance of risk and benefit
► CDM plays a key role in supporting risked-
based monitoring and ensuring data quality
16th Annual Workshop in Japan for CLINICAL DATA MANAGEMENT SMART CDM
February 7-8,2013 | Tower Hall Funabori, Tokyo, Japan
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18. Selected References
Guidance for industry: Guideline for the Monitoring of Clinical Investigations, January 1988
Guidance for Industry Oversight of Clinical Investigations — A Risk-Based Approach to Monitoring
http://www.fda.gov/downloads/Drugs/.../Guidances/UCM269919.pdf
CPGM 7348.810: Sponsors, Contract Research Organizations and Monitors (March 22, 2011), available at:
http://www.fda.gov/ICECI/EnforcementActions/BioresearchMonitoring/ucm133777.htm
CPGM 7348.811: Clinical Investigators and Sponsor-Investigators (December 8, 2008), available at:
http://www.fda.gov/ICECI/EnforcementActions/BioresearchMonitoring/ucm133562.htm
Collins, Rory. (2010, October) Quality Design of Clinical Trials. Presentation at CTTI work stream 3 expert meeting.
https://www.trialstransformation.org/projects/effective-and-efficient-monitoring/developing-effective-quality-systems-in-clinical-
trials-an-enlightened-approach
FDA guidance documents regarding electronic records and signatures subject to 21 CFR part 11
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126953.pdf and the use of computerized systems in clinical
investigations. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070266.pdf
Two studies are on-going as of December 2010 that compare the effectiveness of on-site to alternative (e.g., centralized)
monitoring methods - OPTIMON study: https://ssl2.isped.u-bordeaux2.fr/optimon/Default.aspx
and ADAMON study: http://ctj.sagepub.com/content/early/2009/11/06/1740774509347398.full.pdf
16th Annual Workshop in Japan for CLINICAL DATA MANAGEMENT SMART CDM
February 7-8,2013 | Tower Hall Funabori, Tokyo, Japan
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19. William Gluck, Ph.D.
VP, DATATRAK Clinical and Consulting Services
DATATRAK International
E-Mail: Bill.Gluck@datatrak.net
16th Annual Workshop in Japan for CLINICAL DATA MANAGEMENT SMART CDM
February 7-8,2013 | Tower Hall Funabori, Tokyo, Japan
Confidential –