Embracing Risk in Clinical
Trial Monitoring
James Streeter
Senior Director Life Sciences Product Strategy
HSGBU
October 2, 2014
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The following is intended to outline our general product direction. It is intended for
information purposes only, and may not be incorporated into any contract. It is not a
commitment to deliver any material, code, or functionality, and should not be relied upon
in making purchasing decisions. The development, release, and timing of any features or
functionality described for Oracle’s products remains at the sole discretion of Oracle.
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Strategy
Life Sciences
• Accelerate clinical development
• Support entire drug safety lifecycle
• Enable clinical data aggregation
Healthcare
• Power enterprise healthcare analytics
• Enable provider/payer integration
• Drive personalized medicine
Convergence
• Intersection of clinical trials and clinical care
• Develop collaboration networks for providers
and life sciences companies
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Clinical Research and Development Solutions
Delivering End-to-End Value
Oracle delivers advanced transformative value for clinical R&D in a modular, integrated and scalable
cloud environment and helps you:
Optimize Operations
With technology that helps you
maximize
efficiency across your clinical life cycle
Future-Proof your Business
With a platform that evolves and
grows with you and the industry
Gain Actionable Insights
From aggregated clinical
and healthcare data
Innovate
By incorporating genomics, biomarkers
and real-world patient data
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Risk Based Monitoring
• Embracing Risk in Clinical Trial Monitoring
– Current state of risk-based monitoring
– Why sponsors and CRO’s are shifting to comprehensive, real-time analytics –
•
•
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Integrated with trial management
Mobility
Data from any standards-based EDC system –
The technology backbone to effectively conduct a strategic risk-based monitoring program.
– KRI’s
– Limitations of current eClinical technology
– Challenges
– Summary
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Risk Based Monitoring
• Why Monitoring is required?
– Patient safety
– Eligible patient enrollment
– Protocol compliance
– Accurate data collection
• Paradigm shift…a more targeted, centralized, and risk-based
approach to Monitoring
– Improve resource efficiency
– Increase quality of trial conduct and data collected
– Maintain or reduce study timelines
– Reduce overall study costs
• An industry that has been risk adverse
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Key Drivers for RSDV through technology
– Only 2.4% of critical data is queried on average
– Quality focus
• Site and data
• Increasing safety
– Streamlining drug development
• Getting more drugs to market to help patients
– R&D pipeline
• Reducing risk for financial investment
• 10 to 40% cost savings needed over the next 3 to 5 years
– Travel cost
– Resource cost
– Site time
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• CRO’s
and sponsors
investing millions to implement RSDV
RSDV
Industry
Investments
– Standardizing data and processes
– Creating KRI’s
• Operational focused
• Infancy in what is working and what is not.
– Introducing new business process and change management
• Business Intelligence (BI)tools
– Integrating systems and data – platform approach
• Next focus
– Focus on data quality algorithms, not just operational data
– Business process management tools
– Artificial intelligence
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Industry Initiatives
• Regulatory drivers
– FDA, MHRA, EMA
• Guidance document on eSource Data Collection
• Oversight of Clinical Investigation – A Risk-Based Approach to Monitoring
• Clinical Trials Transformation Initiative (CTTI)
– Quality by design (QbD)
• Transcelerate
– Building QbD into trials
– Early and ongoing risk assessment
– Focus on critical processes and d
– Use of risk Indicators through trial
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Risk Based Monitoring Platform from a Technology /
platform perspective (Current)
Paper, EDC / IVRS
CDM
Monitoring
eTMF
(if separate from
CTMS)
CTMS
Analytic
Systems
Safety / Surveillance
Systems
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Risk-Based Monitoring
Oracle’s Multi-System Holistic Approach
Incorporating customer specific systems
and processes via open interfaces
Upfront risk based trial planning via
ClearTrial
Enabling real-time access to actionable
insights for decision making through
Mobility
Clinical Dashboards & Reports
Mobile CRA
Provide continuous monitoring of
study and site data
ClearTrial
Clinical Development Analytics
Risk Analysis
Customer Portal
Argus Analytics
Empirica Study
Empirica Topics
Extensibility to incorporate data and
programs from customer applications in
the clinical ecosystem (e.g. EDC, CTMS, Lab,
ePro, eTMF, etc.)
Life Sciences Data Hub
Support multiple methodologies for
streamlining site monitoring through
targeted SDV
InForm
OC/RDC
External 3rd Party Data,
Programs
Argus
Siebel CTMS
Suite Integration &
Open Interfaces
Single global safety repository ensuring
risk monitoring of subject safety
Over 80% OOTB coverage of risk
indicators identified in TransCelerate
position paper
Access to historical quantitative and qualitative
site and investigator performance;
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Lower costs leveraging Oracle’s prebuilt integrations and open
interfaces to enable RBM Plans
Risk-Based Monitoring
Oracle’s Multi-System Holistic Approach
Incorporating customer specific systems and
processes via open interfaces
Upfront risk based trial planning via
ClearTrial
Enabling real-time access to actionable
insights for decision making through
Mobility
Clinical Dashboards & Reports
Mobile CRA
GOAL: Enable Life Sciences
Provide continuous
monitoring
of study
customers
to deploy
Centralized
and site data
and Risk Based Monitor Strategies
ClearTrial
Clinical Development Analytics
Risk Analysis
Customer Portal
Argus Analytics
Empirica Study
Extensibility to incorporate data and
programs from customer applications in the
clinical ecosystem (e.g. EDC, CTMS, Lab, ePro,
eTMF, etc.)
InForm
OC/RDC
External 3rd Party Data,
Programs
Argus
Siebel CTMS
Suite Integration &
Open Interfaces
Single global safety repository ensuring risk
monitoring of subject safety
While ensuring
By leveraging existing investments
and Oracle technology to drive
down costs
Empirica Topics
Life Sciences Data Hub
Support multiple methodologies for
streamlining site monitoring through
targeted SDV
Over 80% OOTB coverage of risk indicators
identified in TransCelerate position paper
Access to historical quantitative and qualitative site and
data integrity, subject safety
andperformance;
compliance
investigator
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Drive down costs leveraging Oracle’s
pre-built integrations and open
interfaces to enable RBM Plans
Risk Based Monitoring stages
•Planning
–Identify, plan, and prioritize risk of studying the investigational product.
•Design
–Define protocol eligibility criteria, efficacy, and safety risk factors during design; for inclusion in the eCRF edit build, as well as define
key protocol deviations anticipated for study.
•Execution:
–Clear direction in the oversight and monitoring of parameters leading up to study endpoints, integrated study level monitoring plan,
clear direction on evaluating fraud.
•Analysis:
–Clear definition of data measurement and reporting, defined elements of statistical analysis of protocol endpoints, safety, etc.
•Disclosure
–Publish outcome data, bringing all the above together in the clinical study report (CSR).
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Risk Assessments of investigators, site staff, and sites are
key
• Protocol, a comprehensive risk assessment is essential to ensuring
your risk based
– Identify the risk factors unique to the investigational product, the program and
the protocol.
– Define a risk based strategy,
• Identify the key data,
• Appropriate performance thresholds,
• Determine the appropriate monitoring levels for a specific protocol.
– Risks of the trial only solves part of the equation.
•
The risks of each individual site.
• Comprehensive risk assessment that focuses on site risk factors,
• Set each site up for success by defining a focused risk mitigation strategy.
– Benefits of a risk assessment that includes the evaluation of each site
•
improving site selection by stratifying sites based on key risk factors;
•
establishing early mitigation plans for sites with higher risk;
•
determining a site-specific monitoring level (prior to the study start) that is based on actual data; and
•
assigning monitors and site managers appropriately, based on site risk.
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Access to Data
• We need data at it’s point of origin, original source.
– This allows for real time analysis
– Still using manual/paper/independent collection rather than central sources for collections
– Sites are beginning to have their own EMR, so need ways to communicate with their EMR
• Collect on a central device that can be attached to their EMR and viewed by CRA remotely
• Access to their EMR – however, there EMR may not capture data in the form as specifically as
we require
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Risk Categories & Key risk Indicators
Visit Report Contents
Historical Clinical Data
Current Clinical Data
Site Visit Frequency
TMF Compliance
Data Entry & Approval
Data Cleanliness
SDV
Subject Visits Out of Window
Historical Site Performance
Clinical Supplies
Historical Investigator
Performance
Follow Up Items
Enrollment Rate
Screen Failure Rate
Subject Withdrawal Rate
SAEs
Protocol Deviations
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Key Risk Indicators
• Key Risk Indicators
– Must be in real time
– Must be predictive, reliable and sensitive
– Must be able to trend over time
– Must be able to use data gathered within the study (rates, means, Standard
Deviations) until established thresholds can be determined
– Thresholds may need to be customized by indication, therapeutic area or study
phase
– Need to examine source of that data for reliability
• Deviations self-reported by site not reliable
• Deviations captured by CRA’s while onsite not in real time or predictive
– Need to be able to tap into historical data (site performance on other studies,
similar studies, etc)
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New and Changing Roles
• Remote/Centralized CRA
– Monitors data across sites/subjects
– Compares sites or subjects to other sites or subjects
– May communicate through onsite CRA or may be primary site contact
• Data Analyst
– Monitors data across the study or a program
– Compares study against other studies or subjects against other subjects
– Fraud detection
– Communication passes through PM or CTM to CRA or site
• Blurring/Overlapping of Roles
– DM and CRA
– PVG and CRA
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Challenges to be expected
• Introduction of data with new risks
– EMR and Patient devices
• Introducing historic data outside of clinical studies
• Lack of agreement between clients and vendors on the sharing of data – as a
result of multiple service providers
• This isn’t just about data, but about process and roles which are different
company to company
• As a result sharing data means putting differentiators at risk, particularly for
vendors
• Revenue shift in service providers
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Risk-Based Monitoring Coverage
Oracle’s Platform Approach
Risk-Based Monitoring by Application
Presentation
Applications
OC/RDC
& InForm or
3rd Party
Interactive
Dashboards
Siebel
Clinical
Or 3rd Party CTMS
Ad Hoc
Analysis
Argus
Safety
Or 3rd Party Safety
OBI-EE
Clinical
Development
Analytics
Proactive
Alerts
MS Office
Integration
Mobile CRA
iPhone / iPad
Integration
Emperica
Inspections
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TransCelerate Risk Based Monitoring White Paper
Overview of Oracle Coverage
• Solutions supporting Risk-Based Monitoring Today
– InForm, CTMS, Mobile CRA, Clinical Development Analytics, Argus Safety, Empirica, Argus
Analytics
• Solutions with Risk-Based Monitoring Features Planned
– OC/RDC, CTMS, Clinical Development Analytics, Trial Analyzer
• Coverage of TransCelerate’s Risk-Based Monitoring Methodology by Oracle Solutions
– Over 90% coverage of risk indicators identified in position paper with functionality and metrics
found out-of-the-box in Oracle’s Analytics solutions
• Clinical Development Analytics
• Argus Analytics
– Additional or custom indicators can be easily added to the CDA Warehouse and/or Dashboard
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RBM Summary
• Risk based monitoring is in its infancy
• Regulatory agency are key supporter
• Investments in RBM will continue, standardization is key
• Key Stages- Planning, Design, Execution, Analysis, and Disclosure
• Process and change management investments
• New and changing role
• Real time and historical data access is key
• Platform approach is required
• There will be challenges
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