the fda guidance of a risk-based approach to monitoring as viewed by cdm

8 February 2013

William Gluck, Ph.D. VP, Clinical and Consulting Services

The FDA Guidance of a Risk-Based Approach to Monitoring as Viewed By CDM

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16th Annual Workshop in Japan for CLINICAL DATA MANAGEMENT SMART CDM February 7-8,2013 | Tower Hall Funabori, Tokyo, Japan

Disclaimer

►  The views and opinions expressed in the following PowerPoint slides are those of the individual presenter and should not be attributed to Drug Information Association, Inc. (“DIA”), its directors, officers, employees, volunteers, members, chapters, councils, Special Interest Area Communities or affiliates, or any organization with which the presenter is employed or affiliated.

►  These PowerPoint slides are the intellectual property of the individual presenter and are protected under the copyright laws of the United States of America and other countries. Used by permission. All rights reserved. Drug Information Association, Drug Information Association Inc., DIA and DIA logo are registered trademarks. All other trademarks are the property of their respective owners.

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Agenda

► Historical Perspectives in CDM ► Overview of the Draft Guidance ► A Risked-Based Approach ► Challenges to a Risk-Based Approach ► Supporting a Risked-Based Approach ► Summary

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Historical Perspectives in CDM

► Drug development process • Paper-based processing

► Electronic Data Capture • Interactive processing

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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

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FDA Draft Guidance ► Risk-Based monitoring ► 1988 guidance withdrawn ► Centralized (off-site) monitoring is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

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FDA Draft Guidance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)

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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

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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.”

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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

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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

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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

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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

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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

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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

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Enhance Quality with Technology

Provide multiple training options: Face-to-Face Training Virtual Interactive Training Multimedia e-Training

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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

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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

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William Gluck, Ph.D. VP, DATATRAK Clinical and Consulting Services

DATATRAK International E-Mail: [email protected]