Adequate directions for use "In the Age of AI and Watson"
DIA Issue Management Ken Wu final
1. 1
Controlling the Killer KRI
New Solutions to Address Protocol Deviations
Kenneth Wu, MS, MBA
Clinical Consultant
Kenneth Wu and Associates, LLC
@kennwu
2. 2
• The views and opinions expressed in the following PowerPoint slides are
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Disclaimer
3. 3
I am a subject matter expert consultant to Comprehend Systems, a
technology company with a class of cloud software to help Clinical
Operations.
Financial Disclosure
4. 4
Persistent Key Risk Indicators (KRI) Over Time
Top 3 Critical Findings
# 2000-2006 2007-2009 2010-2012
1
IMP
Compliance
Patient
Selection*
Monitoring**
2
Clinical Study
Report
Source
Documentation
Patient
Selection*
3
Safety
Reporting*
Monitoring**
Efficacy
Assessment*
(Source: http://www.ema.europa.eu/docs/en_GB/document_library/Other/2014/12/WC500178525.pdf)
*Protocol Compliance by Investigator
**Trial Management by Sponsor
5. 5
Consistent KRIs by Inspectors
Top 3 483 Issued
# 2010-2011 2012-2013 2014-2015
1
Protocol
Compliance*
Protocol
Compliance*
Protocol
Compliance*
2
Source
Documents*
Source
Documents*
Source
Documents*
3
IRB Meeting
Minutes
Accountability
Records
IRB Meeting
Minutes
(Source: www:fda.gov/ICECI/Inspections/ucm250720.htm)
*Protocol Compliance and Source Documents by Investigator
6. Confidential and Proprietary: Not for Distribution
Investigators
Monitors
Safety Reps
Data Managers
Multiple
CROs
Slow
Investigation
Limited
Visibility
Don’t Know
Where to Focus
No Audit
Trail
Act
Slowly
Uninformed
Decisions
Distributed
ClinOps
Teams
Biostaticians
Focus on Sites
SILOED OPAQUE DISTRACTED
8. Regulatory Risk Operational Risk
Protocol Compliance Enrollment Site Management
Subject Visit Funnel
Protocol Deviations
Adverse Events
Primary Endpoint Data
Site Activation
Enrollment Funnel, based on
patient status:
Consented
Screened
Randomized
Enrolled
Withdrawn
Evaluable
Monitoring Visits
Data Entry
Query Resolution
Issue Resolution
Drug Inventory
Step 1: Identify KRIs
9. Step 2: Triage
Risk Type High Risk Low Risk
Operational Risk
Enrollment
high screen failure
high withdrawal
slow enrollment
unknown barriers
Site Productivity
non-performing sites
high number of queries
low site performance
aged queries
Regulatory Risk
Protocol Compliance
protocol deviations
unexpected events
low data quality
missing data
Missed Milestones Milestone Achievement
FDA Action FDA Approval
11. Confidential and Proprietary: Not for Distribution
ClinOps
Teams
Fully
Defend
See
Everything
Focus on
What Matters
Actively
Investigate
Act
Faster
Sites
Investigators
Monitors
Safety
Reps
Data Managers
Biostaticians
multiple
CROs
Make Smarter
Decisions
operational/clinical data
Step 4: Validation with Clinical Intelligence
Study Coordinators
Clinical
Intelligence
12. Confidential and Proprietary: Not for Distribution
Use Case: Issue Management
1 Identify Real-time alert when deviations breach configured threshold
2 Triage Composite risk score provides a real-time comparison
3 Analyze One-click analysis: study, issue, and site levels
4 Validate Task management and follow up with audit trail
Protocol Compliance KRI
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Protocol Deviation: Alert and Triage
1
3
4
2
Process Steps
1. Protocol
Deviation
1. Risk Score
18
1. Medtrack
Mount
Center
1. CRA North
America
assigned
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Analyses: Study, Category, Trend
2
1
3
Process Steps
1. Beta 21
Study
1. Prohibited
Concomitant
Medication
1. June 2015
10 prohibited
Concomitant
Medications
were
reported
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Analyses: Outlier and Benchmark
1
2
Process Steps
1. Single outlier
on Prohibited
Concomitant
Medications
1. Canadian
site was
1300%
prohib. con.
meds
(1000x)
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Analyses: Granular Site Trend
Process Steps
1. Prohibited
Con. Meds
violations
high %
1. Appears to
be seasonal
trend
1. Implement
corrective
actions
1
3
2
17. 17
Validation: Audit trail, Continuous Monitoring
Process Steps
1. Audit trail of
corrective
action
1. Continuous
monitoring
1
2
19. Multiple benefits of this approach
Reduce cost of
clinical operations
Minimize trial
cycle time
Increase
productivity
Mitigate
Operational and
Regulatory
Risk
Proactively manage and resolve issues to keep trials on time
20. 20
Kenneth Wu, MS, MBA
Clinical Consultant
Kenneth Wu and Associates, LLC
@kennwu
ken@kenwullc.com
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