cro - clinical vendor oversight webinar
TRANSCRIPT
Webinar
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Agenda
1Recognize the importance of CRO/Vendor oversight
Recognize
2Identify ways to integrate a risk-based approach to oversight
Identify
3Developing an oversight plan with proper KPIs/metrics to be measured
Develop
4Use of tools and technology for accurate and timely reporting
Review
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Our Speaker - Sandra SAM Sather
MS, BSN, CCRA, CCRC
Clinical Operations & Risk Expert
Over 25 years of clinical ops &
training experience
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Sponsor CRO oversight should include risk assessment that includes risk identification at a quality system and project level, and risk prioritization based on the impact, likelihood of error, and the extent to which error would be detectable for identified data and processes.
Project Risk Assessment: The Use of a CRO is Part of the Sponsor Project Risk Assessment
• When is this performed? • By whom? • How often? • Actions Taken?• Documentation?
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November 2013, EMAFinal Reflection Paper on Risk Based Quality Management in Clinical Trials• Purpose of quality management procedures to:
Provide assurance that the rights, safety and well-being of trial subjects are protected
Ensure the results of the clinical trials are credible
• Same requirements apply to others to whom the sponsor has delegated any trial related duties and functions of the sponsor: Contract Research Organizations (CROs) Vendors or other service providers
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Risk-based Approaches Related to Sponsors Working with CROs
Within the FDA Guidance RBM: VI. C. Delegation of Monitoring Responsibilities to a CRO
• [Teaching moment] regulatory requirement for transfer (drug, refer to the FDA CPGM related to device and CROs) and responsibility to retain OVERSIGHT.
• Prospectively consider additional Factors.
• Risk assessment communications bi-laterally of study risk [and risk assessment of CRO performance]
• Risk monitoring and re-assessments clear roles and responsibilities.
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Updates to the FDA Final RBM Guidance related to CRO/Vendor Management Impact
• Impacts vendor management, delegating monitoring obligations to a CRO Requires more clarity, communication,
and evaluation than traditional site monitoring.
Monitoring is not just the monitor, but quality oversight.
• Supports that FDA has communicated goals of RBM to FDA staff and in the BIMO Compliance Program Guidance Manuals (CPGMs).
• Like EMA, focus on quality risk management in sponsor clinical research systems.
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EMA Final Reflection Paper on Quality Risk Management (QRM)Nice Lists of Key Elements of a Clinical Quality System: Documented procedures and validated methods being developed,
implemented and kept up-to date Documentation system that preserves and allows for the retrieval
of any information/documentation (quality records/essential documents) to show actions taken, decisions made and results
Appropriate training of sponsor personnel as well as of the personnel in affiliates, at the CROs, vendors or other service providers and at trial sites
Validation of computerized systems Quality control, for example monitoring of trial sites and central
technical facilities on-site and/or by using centralized monitoring techniques
Quality assurance including internal and external audits performed by independent auditors
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• Sponsor current quality systems include updates to support QRM and oversight related to vendor management/oversight.
• What is expected from the CRO/vendor related to their quality systems and risk assessment.
• Addressing current practices that are not proportionate to the risk nor well adapted to achieving project goals (refer to the slide notes and also EMA Reflection Paper page 5) Avoiding micro-management vs. oversight Base the balance on risk assessment What areas need improvement at sponsor level? What areas are most impacting if CRO lacks or
weak quality system component?
EMA: QRM Requirements Noted that Specifically Apply to Vendor Management
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Common Disproportionate Areas
• Expectation: move towards a more systematic and risk-based approach Move to a more proportionate approach adopted to the risk of the
project. Target limited resources better.
• Both FDA and EMA are asking sponsors and those that perform sponsor requirements/ tasks to take QRM practices and clinical quality systems from GMP to GCP. ICH Q9 (QRM) and Q10 (QS)
• So, do sponsors increase risk to your CROs/vendors by poor design of protocol, or over interpretation of the regulations?
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New QRM Requirements’ IMPACT
• Applies to those that perform sponsor GCP functions• Safety, data management, monitoring, etc.• Not just the Monitor
• But also affect the selection of CROs/Vendors • e.g., Request for Information (RFI), Request for Proposal
(RFP), contracts, transfer of responsibilities (TOR), scope of work (SOW).
• And oversight of CROs /vendors by a sponsor• e.g., project deliverables, project reports,
communication, etc.
• Adjust clinical processes related clinical QRM Vendor assessments and evaluations RFI and RFP Escalation policy Risk assessment of vendor involvement Communication plans
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Flow of QRM in GCP
PLAN
DOCHECK
ACT
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Quality Risk Management (QRM)
Respond to deviations
Measure/monitor Study conduct
Identify quality objectives and metrics and risks to quality to develop quality management plans (e.g., Vendor Oversight Plan, CRO Project Plan)
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Integrating Risk Management Process Flow with Flow of GCP Vendor Oversight [ISO/ ICH]
I M P A C T A N A L Y S I S
• Cross-functional team
• Risk Management Leader(s)
• Risk Tool / Platform
• Risk Assessment (Compliance, Financial, etc.)
• Link to historical data from metrics / audit findings
Organization Level QRM
Pre-study
Develop Study Risk Management Plan (MP, DMP, SMP, etc.
▪ List of potential threats
▪ Risk assessment• Product• Disease• Patient• Self• Sponsor• IRB
During the Trial
Plan(s) Management Timeliness of data
completion• Enrollment• AE • Deviation • Audit results• Noncompliance• Staff turn-over• Risk mitigation
adjustment
Study Closure
• Enrollment outcomes
• Deviations outcomes
• Audit readiness
• Metric adjustment from Risk Management Plan statistics
Re-Assess & Adjust
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(EMA) STEP I: Risk Identification
2 levels considered when gathering information for clinical trial risk identification (EMA, 2013)• 1st level = system risk
Information associated with the environment and its systems should be analyzed to identify potential risks that could affect organizations, their technology and their data and products.
Indirectly affect a clinical trial. • 2nd level = project risk
Information directly linked with the trial should be analyzed to identify the risks that are trial specific
PLAN
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1st level = Systems Risk
EMA, Nov 2013: organization structures and responsibilities (e.g. organograms,
communication plans, contractual partners) quality systems and processes (e.g. standardized procedures) facilities and computerized systems (e.g. Information technology
infrastructure, document management system, data management system, IVRS, eCRF system)
human resources including training and qualifications of personnel (e.g. job descriptions, training plans, performance management)
compliance metrics, performance measurements, quality audit and/or inspection outcomes
regulatory and ethical framework (e.g. knowledge of national and local approvals and notification required and their timelines)
Includes Sponsor & CRO system risks• RFI / RFP • SOW & Project Plan(s)
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2nd level = Project / Trial Risk
EMA, November 2013: Single clinical trial or full development program• investigational medicinal product(s) [IMP];• trial design and protocol specific requirements; • operational:
study budget, deadlines, staff numbers and talent, project management (e.g., multi-vendor), resources and the training (e.g., outsourcing to CRO), equipment and technology, trial or product specific procedures/methods
Includes Sponsor & CRO system risks• RFI / RFP • SOW & Project Plan(s)
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For CRO Management: What Are the Areas of Greatest Risk & Likely to Occur?
Sponsor contributed
• System Level
• Project Level• Pre-study• During• End of
study
CRO contributed
• System Level
• Project Level• Pre-study• During• End of study
Early meeting with the CRO to do a project risk assessment. Risk Assessment to Fishbone the 6 main areas of risk (that rank high enough based on severity and likelihood, timing), and identify root cause and verify interventions and detection mechanisms are in place.
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• For a study where a sponsor has contracted a CRO to do study monitoring, who should perform the study/projectrisk assessment?
A. SponsorB. CROC. Both D. NeitherE. Depends F. Not Sure
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• For a study where a sponsor has contracted a CRO to do study monitoring, who should perform the site risk assessment?
A. SponsorB. CROC. Both D. NeitherE. Depends F. Not Sure
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Step II: Establishing Priorities for Risk Evaluation
PLAN
Project Risk Assessment: • Does the sponsor prioritize / evaluate for the CROs
related to their assigned / contracted sponsor responsibilities? Or is this micro-management.
• Or does the sponsor review and approve the CROs step II? How would this be communicated and overseen? Ideally this should be the CROs job.
Step II for sponsors oversight systems• Be sure that prioritization of sponsor CRO oversight
activities are based off actual risk assessment, not because we “always do it a certain way” or no way.
• Oversight activity prioritization.
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Step III: Risk Control
DO
• Sponsors evaluate if CROs do this related to their assigned / contracted sponsor responsibilities (SOW). How would this be communicated and overseen?
• For sponsors oversight systems involve risk control related to CRO oversight, not performing sponsor responsibilities, unless from assessment that is the safest alternative.
• Sponsors evaluate if CROs do this related to their assigned / contracted sponsor responsibilities. How would this be communicated and overseen? For sponsors oversight systems involve risk control
related to CRO oversight, not performing sponsor responsibilities, unless from assessment that is the safest alternative.
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Risk Control: Alternative Oversight Techniques
DO
• Communication with Vendor / CRO– Encourages various modes of communication at
Specific study time points and activities. Work products linked to mitigation interventions
and metrics for tolerance levels.
• Review of CROs Processes, Procedures, and Records Using Central Monitoring Techniques– eTMF– CTMS
• Milestones and Critical Data Points– Define what are critical study parameters and how will
they be reported vs. all data. – Clearly define what is pertinent info to support oversight
not micromanagement. – Does NOT decrease the requirements of sponsor
regulatory application responsibilities
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Step IV: Quality Tolerance Limits
CHECK
• Who establishes tolerance limits? Data vs. Oversight
• Who tracks, evaluates root cause of deficiencies / violations and intervenes?
• Who determines metrics? Good to ask what are quality metrics used by CRO during RFI and/or RFP. Traditional vs. post RBM.
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Quality Tolerance Limits continued…
Examples of areas for which variation or tolerance limits could be established and linked to the CRO reports to Sponsor: 1) Trial data, 2)Trial protocol procedures and GCP 3)Trial management procedures
Define the metrics that will allow oversight of the trial
Establish the oversight strategy
Include escalation plans and communication strategy to ensure quality tolerance triggers lead to sponsor notification (reading MVR, outlying performance, change in staff, etc.)
Sponsors should have established action plans for quality tolerance deviations (e.g., may be part of a vendor oversight plan, or within the quality risk management plan)
Define the timing of CRO sponsor reporting/retrieval of data
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Step V: Risk Review Cycle
ACT
Concept of risk based clinical quality management revolves around the following cycle
1. risk assessment with information gathering, the establishment of priorities and the identification of risks associated with the study;
2. risk control which encompasses setting tolerance limits mitigation and acceptance of risks;
3. risk review which necessitates knowledge of the previous steps with the integration of the risk management tools and the communication on the review of the results and data associated to the risk identified and the documentation of the actions needed.
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Summary
• Recognize the importance of CRO/Vendor oversight in clinical trial management.
• Identify the ways to integrate a risk-based approaches to CRO/Vendor oversight.
• Developing a CRO/Vendor oversight plan with appropriate KPIs/metrics to be measured.
• Use of tools and technology for accurate and timely reporting.• Steps of CRO/Vendor Oversight with a Risk-based Approach
Step I Risk Identification Step II Risk Prioritization Step III Risk Control Step IV Quality Tolerance Limits Step V Risk Review Step V Reporting Quality
Metrics …
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Balancing Dilemma ..
What gets measured gets
fixed
Analytical mindset
When there is too much information to process, we tend to use “common sense,” or “educated guesses.” But, when we use common sense, we tend to be biased.
Logical mindset
Metrics that help organizations overcome common challenges like excessive workloads, rework, unclear or changing requirements, and disappointing
outcomes in services, products and finances.
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Right mix of Types
Measure Processes, not People
Big picture in mind
Define. Define. Define Start Simple
Through out the process, keep asking “so what”
Purpose of Measurement ?Answer this first before starting any steps …
TAT, QualityCycle Time, Efficiency
Leading & Lagging Indicators
Dive into calculations. Be on same page.
B
A
COutput
from C -> D
Output from A->B
Output from B -> C
D
Multiple Vendors… your View
..their View
OperationalLevelAgreement
OLAs are agreements between different Vendors (and/or your internal business functions)
(where as, Metrics, also known as SLAs, are the overall agreement between Vendors andyour Organization)
A
B
C
D
...time bound Accountability
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Quick Comparison
SLAs address the Business Level Requirements, e.g. "After Agreements signed, FPI completes in 8 weeks".
For business it is not of interest, how many days are needed by the different vendors, e.g. CRO vendor for site negotiations, EDC vendor for DB live, Patient recruitment vendor to start the advertisements.
These details must be defined in the OLAs which the Organization (can be represented by an Outsourcing manager or an Alliance manager or Procurement or Program/Project manager) needs to negotiate and agree with all involved vendors.
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Data-driven Decision making
You do not have time to spend extracting information from several reports from several vendors (and sometimes poorly designed or inappropriate Charts).
Performance metric reports should highlight critical data and provide the user (that’s you) with the confidence to make decisions that will improve processes and deliver results.
Key is to have this info come to you INTEGRATED..
.. and in REAL TIME
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Joint CommitteeYou Vendor
Clearly structured model to steer the partnership for a successful collaboration between YOU and VENDOR
Strategic(quarterly)
Alliance Committee
YourExec
Management
VendorExec
Management
Tactical(Daily business)
Support &Ops Leads
Development Ops Teams
Project(monthly)
OperationsCommittee
ProgramManagement
Project Manager&
Functional Leads
Reporting
Governance
