Presented By
William Gluck, Ph.D.
VP, DATATRAK Clinical Knowledge
DATATRAK International, Inc.
Risk-Based Monitoring in Pr...
Confidential –
Dr. Bill Gluck
► Dr. Gluck has over 30 years of leadership experience in the
Life Sciences industry, and br...
3
Review of the Risk-Based
Guidance Document
How the Guidance is Re-
Defining How Studies are
Conducted
Insights to
Implem...
4
http://www.fda.gov/Drugs/GuidanceComplianc
eRegulatoryInformation/Guidances/default.htm
History of Guidance Document
• R...
5
Guidance
Document
General
Points:
Guidance focuses on monitoring – only one aspect of the
clinical trial process
Monitor...
6
Approaches to
Monitoring
On-Site Monitoring – an in-person evaluation
Centralized Monitoring – a remote evaluation
7
On-Site
Monitoring
Assurance that
subjects and
study documents
exist
Sense of Quality
of overall conduct
at a site
Early...
8
Centralized
Monitoring:
Alternative
Monitoring
Techniques
Monitor through routine review of entered data
Conduct statist...
9
Alternative
Monitoring
Techniques:
Other
Areas of
Focus
Communication with Study Site Staff
Review of Site Processes and...
10
How the Guidance is Re-Defining
How Studies are Conducted
11
The
Guidance:
Focus on
Monitoring
No single approach works
Tailor monitoring plans to study – focused on
specific subje...
12
• Overall support and guidance
• Protocol developmentClinical R&D
• Sponsor Team Members
• Sites and Site Team Members
...
13
Insights to
Implementation
14
Risk
Assessment
Identify the risks
Analyze the risk
Implement controls
15
Assessing
Risk for
Monitoring
Guidance
Discusses risk assessment in the context of
clinical monitoring
As noted: identi...
16
Factors to
Consider in
Developing
Monitoring
Plans
Complexity of the Study Design
Types of Study Endpoints and Quantity...
17
Key
Components
of a
Monitoring
Plan
Description of Monitoring
Approaches
Communication of Monitoring
Results
Management...
Confidential – 18
Monitoring Plan Template
Study Protocol:
Stage/Phase of Study:
Introduction:
Brief description of the st...
Confidential – 19
Management of Noncompliance:
Describe the process for addressing challenges of noncompliance or the reso...
20
Additional
Strategies
to Help to
Ensure
Study
Quality
Protocol and CRF Design
Training and
Communication
Delegation of
...
Confidential –
Sample Risk Assessment Worksheet
21
Risk Assessment
Worksheet
Risk Area/Category Potential Risk Assessed
Ri...
Confidential – 22
Risk Area/Category Potential Risk Assessed
Risk Examples (list study specific
issues)
Include in
Monitor...
Confidential – 23
Budgetary constraints
Does the budget allow for
adequate time and resources to
conduct the study, monito...
Confidential – 24
Study Conduct Quality Management System-Sponsor Level
Is there a sponsor level QMS in place, at the
CRO/...
Confidential – 25
Investigational Product
Is there investigational product in place to conduct the study, is
there a re-su...
Confidential – 26
Performance Metrics
Time of entry after study participant visit, time of query
resolution/response, etc....
Confidential –
List of Selected References
http://www.fda.gov/downloads/Drugs/.../Guidances/UCM269919.pdf
http://www.mhra....
28
Summary
1. Risk-Based Monitoring is focused on monitoring
2. Regulatory bodies want to promote flexibility and the abil...
29
William Gluck, Ph.D.
VP, DATATRAK Clinical Knowledge
DATATRAK
E-Mail: Bill.Gluck@datatrak.com
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Risk Based Monitoring in Practice

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After reviewing the FDA regulations on Risk Based Monitoring, review the details on how to put the principles into action! We include two reference documents to help you get started... and to make it a success.

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Risk Based Monitoring in Practice

  1. 1. Presented By William Gluck, Ph.D. VP, DATATRAK Clinical Knowledge DATATRAK International, Inc. Risk-Based Monitoring in Practice 5/29/2014 1www.datatrak.com
  2. 2. Confidential – Dr. Bill Gluck ► Dr. Gluck has over 30 years of leadership experience in the Life Sciences industry, and brings his expertise in the field of Risk Based Monitoring to DATATRAK. ► Dr. Gluck has held management roles in sponsor companies, including Amgen, BASF Corporation, Gilead Sciences, and Triangle Pharmaceuticals. Dr. Gluck also has expertise with CRO organizations, having served in senior management roles for seven years. ► Dr. Gluck began his career in academia at the university level, and now serves as the Program Director for the Clinical Trials Research and Medical Product Safety/Pharmacoviligance programs at Durham Technical Community College. ► Dr. Gluck has a Bachelor of Science degree from the University of Scranton and Master and Ph.D. degrees from North Dakota State University. 2
  3. 3. 3 Review of the Risk-Based Guidance Document How the Guidance is Re- Defining How Studies are Conducted Insights to Implementation
  4. 4. 4 http://www.fda.gov/Drugs/GuidanceComplianc eRegulatoryInformation/Guidances/default.htm History of Guidance Document • Replaced 1988 Guidance on Monitoring • New RBM Draft Guidance August 2011 • Final RBM Guidance August 2013
  5. 5. 5 Guidance Document General Points: Guidance focuses on monitoring – only one aspect of the clinical trial process Monitoring is a quality control tool FDA defines monitoring as the methods used for the conduct of and reporting of data from clinical investigations Stronger support of risk-based monitoring approaches are clearly stated FDA recommends a quality risk management approach to clinical trials The risk-based approach is dynamic and can facilitate continual improvement in trial conduct and oversight Expect risk-based monitoring to enhance data quality
  6. 6. 6 Approaches to Monitoring On-Site Monitoring – an in-person evaluation Centralized Monitoring – a remote evaluation
  7. 7. 7 On-Site Monitoring Assurance that subjects and study documents exist Sense of Quality of overall conduct at a site Early in the study Complete administrative and regulatory tasks Centralized Monitoring Remote activities Targeted on-site monitoring Review of data in real-time Verify source data remotely Conduct aggregate statistical analysis of study data Conduct analysis of sites, performance, and data Complete administrative and regulatory tasks Types of Monitoring
  8. 8. 8 Centralized Monitoring: Alternative Monitoring Techniques Monitor through routine review of entered data Conduct statistical analyses to identify data trends Analyze site characteristics, performance measures, and clinical data to identify potential characteristics associated with noncompliance and poor performance Verify critical source data remotely, when source data are available Complete administrative and regulatory tasks
  9. 9. 9 Alternative Monitoring Techniques: Other Areas of Focus Communication with Study Site Staff Review of Site Processes and Procedures a. Informed Consent b. Site Records Source DataVerification and Corroboration
  10. 10. 10 How the Guidance is Re-Defining How Studies are Conducted
  11. 11. 11 The Guidance: Focus on Monitoring No single approach works Tailor monitoring plans to study – focused on specific subject protection and data quality Assess critical data and processes – informed consent and eligibility criteria Assess critical data and processes – documentation of accountability and administration of investigational products Assess critical data and processes – focus on trial integrity…processes such as maintaining the study blind
  12. 12. 12 • Overall support and guidance • Protocol developmentClinical R&D • Sponsor Team Members • Sites and Site Team Members Clinical Study Team • Sponsor CRA’s or designated CRO representatives • Site key personnelCRA/Site • Clinical Data Management • Biostatistics • Regulatory, Quality, Compliance Support Services Key Roles and Responsibilities
  13. 13. 13 Insights to Implementation
  14. 14. 14 Risk Assessment Identify the risks Analyze the risk Implement controls
  15. 15. 15 Assessing Risk for Monitoring Guidance Discusses risk assessment in the context of clinical monitoring As noted: identifies analyses, and implements controls to manage risk Does NOT provide comprehensive detail on how to perform risk assessment Risk Assessment Methodologies Guidance for Industry, Q9 Quality Risk Management, June 2006. ISO 31010:2009 Risk Management – Risk Assessments Techniques Risk Identification for Monitoring “…consider the types of data to be collected, the specific activities required to collect these data, and the range of potential safety and other human subject protection concerns…” Assess and prioritize risk: a. likelihood of occurrence b. impact on safety and trial integrity c. extent to which errors would be detectable
  16. 16. 16 Factors to Consider in Developing Monitoring Plans Complexity of the Study Design Types of Study Endpoints and Quantity of Data Clinical Complexity of the Study Population and Geography Relative Safety of the Investigational Product Stage of the Study Experience of the Sites and the Sponsor Ability of LeverageTechnology
  17. 17. 17 Key Components of a Monitoring Plan Description of Monitoring Approaches Communication of Monitoring Results Management of Noncompliance Ensuring Quality Monitoring Plan Amendments/History of Plan Changes or Modifications
  18. 18. Confidential – 18 Monitoring Plan Template Study Protocol: Stage/Phase of Study: Introduction: Brief description of the study landscape – geography of the sites, anticipated reach of the population, potential challenges in terms of enrollment and compliance by both study participants and sites. Description of Monitoring Approaches: Include in this section a description of the monitoring methods to be employed especially noting how the critical elements/data points/end points will be collected. Note too and risks involved and how these risks might be mitigated (at a high level). Also include the timing and frequency of the various approaches you are planning and how changes will be made and communicated through the study team. In this section also include what the threshold are for action or those specific trigger points that might require a site to be monitoring on a more frequent basis. Also include definitions for deviations and how they should be reported and recorded. Communication Plan: Describe how reports and monitoring results will be communicated throughout the team. Identify/Define specific standard reports and how and when they will be generated and then communicated. Also include an escalation process of communication should the need arise or unforeseen challenges emerge during the course of the study.
  19. 19. Confidential – 19 Management of Noncompliance: Describe the process for addressing challenges of noncompliance or the resolution of significant issues that have not yet been resolved. Again build upon the communication escalation process to make sure that there is an escalation process in place should it be necessary. As part of the process, in this section you should also describe a procedure to conduct a root cause analysis and how the issue will not resurface later in the study. Quality Monitoring Process/Plan: In this section describe the specific training and qualifications needed of all study team participants from the sponsor’s perspective through to each site perspective. Planned audits of monitoring across several levels should be defined as well as a description of the process in case there is a need for an unplanned or for cause audit. Also included in this section should be the plan for co-monitoring trips or oversight to ensure consistency of monitoring and compliance to documented monitoring processes and procedures. Amendments
  20. 20. 20 Additional Strategies to Help to Ensure Study Quality Protocol and CRF Design Training and Communication Delegation of Responsibilities Site Selection and Interaction
  21. 21. Confidential – Sample Risk Assessment Worksheet 21 Risk Assessment Worksheet Risk Area/Category Potential Risk Assessed Risk Examples (list study specific issues) Include in Monitoring Plan (Yes/No) Tolerance Threshhold
  22. 22. Confidential – 22 Risk Area/Category Potential Risk Assessed Risk Examples (list study specific issues) Include in Monitoring Plan (Yes/No) Tolerance Threshold Study Planning Study protocol development and related essential documentation How complex is the protocol, are there anticipated amendment points, process of unintended amendments, process for the collection, review, and management of FDA/ICH GCP related essential documents, etc. Is there a clear understanding of roles and responsbilities, transparancy in communication and expectations?
  23. 23. Confidential – 23 Budgetary constraints Does the budget allow for adequate time and resources to conduct the study, monitoring, other study activities? Are the contracts associated with all supportive facets of a clinical study available and/or in place? Is there legal support if applicable? Site identification/Feasibility Based on the study protocol can sites be easily identified, is the needed study population obtainable, are the site reliable in terms of attracting and qualifying potential study participants,etc. Site Qualifications Qualifications of the principal investigator/clinical investigator, qualificiation of the site overall - are the proper site processes and procedures in place, are the site personnel trained, experience and qualified, etc. Vendor Qualifications Qualifications of the vendor (is this a core support service), qualification of the vendor overall - are the proper processes and procedures in place, are the personnel trained, experience and qualified, etc.
  24. 24. Confidential – 24 Study Conduct Quality Management System-Sponsor Level Is there a sponsor level QMS in place, at the CRO/support company level, at the site level? Required Regulatory Reporting Does the sponsor have the infrastructure to support the required regulatory reporting needed? Does the supporting organization have the infrastructure? Does the site have a QMS or the essential quality controls in place? Specific Study Activities Informed consent process, enforcement of INC/EXC, handling protocol deviations/violations, stopping rules, SAE handling, dose modifications, etc.
  25. 25. Confidential – 25 Investigational Product Is there investigational product in place to conduct the study, is there a re-supply process, is the supply chain establsied, are there regulatory risks for international studies/transport/storage of the investigational product? Safety Concerns Study participant protection and well-being processes/procedures in place, safety monitoring, know adverse evetns/reactions, process for documetnation and reporting of unexpected events and SAE's Study specific tasks Endpoints, complexity of the study, stage of the study, number of potential study participants and geographic availability
  26. 26. Confidential – 26 Performance Metrics Time of entry after study participant visit, time of query resolution/response, etc. Quality Metrics Number of queries needed, number of re-queries needed, etc. Biostatistics and CDM concerns Technology availability and evaluation, quantity of data, clear identification of endpoints and collection of needed study data, identification and generation of reports, data transfer, internal filtering etc., availability and use of standards such as CDISC (STDM).
  27. 27. Confidential – List of Selected References http://www.fda.gov/downloads/Drugs/.../Guidances/UCM269919.pdf http://www.mhra.gov.uk/home/groups/l- ctu/documents/websiteresources/con111784.pdf http://www.transceleratebiopharmainc.com/wp-content/uploads/2013/09/Risk- Based-Monitoring-Methodology-Position-Paper.pdf http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline /2011/08/WC500110059.pdf http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Effica cy/E6_R1/Step4/E6_R1__Guideline.pdf http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Qual ity/Q9/Step4/Q9_Guideline.pdf 27
  28. 28. 28 Summary 1. Risk-Based Monitoring is focused on monitoring 2. Regulatory bodies want to promote flexibility and the ability to explore new methods for monitoring and to leverage advances in technology where applicable 3. It is anticipated that there will be continued use of on-site monitoring but also anticipate the evolving use of technology and monitoring methodologies to achieve heighted levels of study participant safety and increased levels of data quality
  29. 29. 29 William Gluck, Ph.D. VP, DATATRAK Clinical Knowledge DATATRAK E-Mail: Bill.Gluck@datatrak.com
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