risk based monitoring - a holistic approach to late phase studies
TRANSCRIPT
Risk Based Monitoring – A holistic approach to late phase studies Thursday, May 16, 2013
About ICON
• ICON plc is a global provider of outsourced development services to the pharmaceutical, biotechnology and medical device industries.
• The company specializes in the strategic development, management and analysis of programs that support clinical development - from compound selection to Phase I-IV clinical studies.
• ICON currently operates from 79 locations in 37 countries and has approximately 10,045 employees.
• Further information is available at www.iconplc.com
ICON Signature Series
• ICON Signature Series is our thought leadership program that offers expert insights into value-driven strategies for clinical development.
• The program features ICON and external experts in all aspects of clinical development and post-approval product value strategies.
• For a list of featured topics and upcoming events go to: http://www.iconplc.com/icon-views/
Upcoming Webinars
• Biomarker Strategies for More Efficient Early-Phase Drug Development in Alzheimers Disease
21st May, 2013, 11:00 a.m.- 12:00 p.m. EST
• Current Challenges in Oncology Trials: The new EMA Guideline on the Evaluation of Anticancer Drugs in Man
29th May, 2013, 11:00 a.m. – 12:00 p.m. EST
• Cardiovascular Outcomes Trials - State of the Art4th June, 2013, 11:00 a.m. – 12:00 p.m. EST
• Biosimilar availability and Price & Access Implications12th June 2013, 11:00 a.m. – 12:00 p.m. EST
• Circulating Tumour Cell Testing13th June, 2013, 11:00 a.m. - 12:00 p.m. EST
• To register visit: http://www.iconplc.com/news-events/events/webinars/
Introductions
Tim Clark
Vice President Scientific AffairsICON Clinical Research
Lee King, Vice President, Project Operations and Strategic Programs
Malcolm BurgessExecutive Vice President, ICONIK
What we will discuss.
• Regulatory Landscape
• Considerations for a holistic approach to Risk Based Monitoring
• Maximized Efficiencies
• The role of Technology
Agenda
Regulations designate responsibility for assurance of data quality during the conduct of clinical trials regardless of phase.
• Joint Responsibility– Sponsor
• “Sponsors are responsible for…ensuring proper monitoring of the investigation(s)” 21CFR312.50
– Participating Physician• “An investigator is responsible for ensuring that an investigation is conducted
according to the signed investigator statement” 21CFR312.60• “The investigator should develop a plan for supervision…which might include..
(procedural guidance October 2009)– A procedure for ensuring that source data are accurate, contemporaneous and
original– A procedure for ensuring that information in source documents is accurately
captured on the CRFs– A procedure for dealing with data queries and discrepancies
Regulatory Authorities have recognized the growing need for risk based monitoring and offered industry guidance.
HolisticAdjective
Characterized by comprehension of the parts of something as intimately interconnected and explicable only by reference to the whole1
1GoogleSearch
Protocol Design
Source Document Verification Plan
Site Management
Data Monitoring
Risk Management
Holistic Risk Based
MonitoringStrategy
A holistic approach to risk based monitoring focuses on all data and process. aspects of a study or trial.
Protocol Design
Holistic Risk Based
MonitoringStrategy
Beginning with the end in mind is crucial to success when implementing a holistic approach to risk based monitoring.
• Critical data identification to support primary analysis
• Patient safety
• Treatment Schedules
• Other data requirements• HEOR• PRO/QOL
Source Document VerificationPlan
Holistic Risk Based
MonitoringStrategy
An effective SDV plan must be flexible and adaptive based on complexity factors at the site level..
• Study Phase and/or Complexity• Primary Endpoints• Targeted SDV Plan
• Random• Frequency• Endpoint• QC
• Adaptive Operations• Triggers for SDV expansion• Additional Trainings• KPIs
Site Management
Holistic Risk Based
MonitoringStrategy
Effective and integrated site management is a crucial component to an holistic risk based monitoring approach..
• Physician and Site Experience• Historical performance• Training visit requirements
• Integrated into Data Monitoring• Single point of contact
• Communication Plans• Scheduled Interactions
• KPI Acceptance• Adaptive Operations
• Patient Recruitment• Data Logistics• Product Management
Data Monitoring
Holistic Risk Based
MonitoringStrategy
Remote monitoring integrated with site mgmt. ensures data quality, eases site burden and leverages expertise..
• Centralized Remote Review• Frequency and Volume• Query Management• Study closure
• Integrated with site mgmt.• Single point of contact
• Integration of all data sources• Safety• Lab• PRO/eCOA• IVR/IWR
Risk Management
Holistic Risk Based
MonitoringStrategy
Risk Management must be proactive and routine for effectiveness in holistic risk based monitoring approaches
• Proactive at all phases of study• Plan for reinforcement
needs before they happen
• Differentiate outliers versus systemic issues
• KPIs can drive analysis at study, site or staff level
• Query rates• Protocol Deviations• Drop out rates• Data findings
Driving the evolution:
2013 “Trusted Advisor” Implementation Plan
The Role of Technology in Risk Based Monitoring
Leveraging appropriate technology focused on Time/Cost/Quality important when using RBM in late phase.
System FunctionalityFocused on User interface, automation and
reporting
• Logic driven user interface for research naïve sites
• Quick set up time (4‐6 weeks)
• Field Level Sign off for risk based monitoring
• Integrated ePRO capabilities
• Automated Communications
Alternative costing models can alleviate pricing pressures for longer term studies inherent in the late phase space.
CostFocused on the variety of different types of late
phase projects, i.e. interventional vs NIS
• Interventional PIIIb and PIV
• Observational Studies
• Mega Trials
• Medical Device Studies
• Cohort Studies
• License structure based on number of data points vs traditional site/month method
• Interface reduces help desk support to L3 only
• Training efficiencies built in for multiple project programs
EHR integration enhances abilities to further define holistic risk based monitoring approaches and contain project costs.
Standards and QualityFocused on adherence to industry data
management standards for data reporting
CDISC
RFDCompliant
Workflow IntegrationAllows site stakeholders to access the platform directly from the electronic patient chart.Allows site stakeholders to search EHR database for observational study candidates based on inclusion/exclusion criteria.Reduced site training
Data IntegrationAllows the pre-population of EDC forms directly from the EHR dataReduced data entry (site level) and DM costs
ICON utilizes an integrated information platform which helps to maximize efficiency while maintaining quality
TransparencyIncreased transparency to
clients throughout the development process
VisibilityAccurate and detailed information
on site performance and risk
Operational EfficiencyAutomated processes to gather and
surface information
QualityIncreased focus on data integrity and
control of clinical data
ICONIK’s use of repositories centralize multi-source data for a holistic monitoring approach.
Stu
dy
A
Stu
dy
B
Stu
dy
C
Study Data Mapper
CTMS IVREDC LabsIMI
Stu
dy
DStandardize
Data RepositoryCentralize
Safety Metrics
Risk Indicators
LaboratoryData
Quality MetricsRecruitment
Visualize
Integrated reporting allows for adaptive operational approaches in areas such as patient recruitment at the site level.
Screened
Randomized
Comparative reporting can also highlight outliers or identify areas for additional training.
Total years of subject exposure
AE count
Comparative reporting can also highlight outliers or identify areas for additional training needs.
Unique BP recordings
Total number of BP recordings
An effective holistic risk based monitoring approach is anchored by adaptive operational methods at the site level.
sites
% SDV & On-Site Activity
Holistic Risk Based Monitoring not only serves to ensure data quality; but also, contain project costs.
Targeted IMVs
Risk-based strategy (~7 visits per site
(life of study)
CRF size = 100 pages
Total approximate site visits = 2,520
Total Clinical cost: $46,520,000
ICON Strategy7 IMVs per site 1st year
IMVs every 10-12 weeks per site
CRF size = 125 pages
Total approximate site visits = 9,000
Total Clinical Cost: $66,634,057
Initial Specifications
• In order for a Risk Based monitoring approach to be holistic, it must consider all aspects of a study versus just onsite monitoring or SDV.
• Remote Review of study data should be centralized and integrated with site management to recognize efficiencies and leverage appropriate clinical expertise.
• Cross functional Key Performance Indicators should be utilized when developing a holistic approach.
• The ability to integrate and review data from multiple sources is paramount for efficient implementation of a risk based monitoring approach.
In Summary
