This document discusses risk-based monitoring (RBM) in clinical trials. It defines RBM and explains how it can reduce monitoring costs by up to 30% compared to traditional monitoring methods. RBM uses risk profiles and key risk indicators to determine monitoring needs and focus on-site visits on higher risk areas. This improves data quality and trial efficiency. The document also outlines Cyntegrity's RBM services and how their EarlyBird software system can automate RBM to further reduce costs while maintaining data integrity and patient safety.

1. Cyntegrity, 2016
Artem Andrianov
CEO Cyntegrity
LIFE DATA INTEGRITY
RBM - the Light Side
Ways of Trial Optimization
Application of Data-driven
Risk-based Monitoring

2. “May the force be with you”
(Master Yoda)

3. What is Risk-Based Monitoring (RBM)?
• Monitoring have to be done by law (GCP);
• Monitoring is 1
3−𝑟𝑑 of clinical trial costs
RBM:
Clinical Sites
Monitor (CRA)
Risk Profiles
On-Site Visits
Reduced Monitoring
Traditional:
Clinical Sites
Monitor (CRA)
On-Site Visits

4. Internal and External Risks
Internal Risks
Company
External Risks
4

5. Alarm! + CAPA
Right Actions in Right Time

6. Cost of Outsourcing by Function
Major cost-saving potential

7. RBM Required by Regulatory
1. FDA in 2013
2. EMA in 2014
3. GCP Addendum published in 2015
* Source: ICH Harmonised Tripartite Guideline, Guideline For Good Clinical Practice E6(R1), Addendum Draft
“The sponsor should develop a systematic, prioritized, risk-based approach to monitoring
clinical trials. A combination of on-site and centralized monitoring activities may be appropriate.
(...)
Centralized monitoring is a remote evaluation of ongoing and/or cumulative data collected from
all trial sites in a timely manner. Emerging advances in technology may facilitate the remote
monitoring of source data when appropriate.”*

8. How RBM Influences a Trial?
Costs reduction in a long run, through
recruitment fewer patients, data quality
improvement and control under "risky
situations" like
e.g. sloppiness and protocol violation.
Control and improvement of clinical data quality,
as a result, narrow confidence intervals of a
clinical trial by means of reducing “data noise”.
I.e. Better chances to reach statistical
significance of a trial's outcome.
Building up a Knowledge Base of To-do actions
from study to study letting inexperienced CRAs
be effective from the first day.
"On-the-fly" applying of KRIs from other
Sponsors (even in the middle of a trial).
Compliance with GCP Addendum, FDA and EMA
monitoring guidances.
More efficient risk communication
within company.
*”Risk-based monitoring: Reduce clinical trial costs while protecting safety and quality,” PwC. [Online].
Available: http://www.pwc.com/us/en/health-industries/publications/pharmaceutical-development-risk-based-monitoring.html. [Accessed: 14-Oct-2015].

9. Technology plays a
critical role in effective
risk-based monitoring.
However, the
monitoring team is
equally important.

10. Technology Essential Features
Risk Management
Data Quality Monitoring
Site Ranking
• Umbrella Principle – unification of CTMS, EDC, etc.
• Risk mitigation communication
• Concentration on systemic risk, not random artefacts
• P-value control for essential variables
• Geographical quality spread
• Data quality dynamics and comparison values
• Transparent communication and site involvement
• Historical Root-Cause feedback graph

11. Value Proposition for Sponsor
Keeping data clean
• Increases efficiency by reducing the need for corrective actions
• Narrows the confidence intervals
• Improves the chances to reach statistical significance
Remote 100% data-
monitoring
• Improves the job-quality of CRA, allows more remote work
• Reduces monotonous checks
• Adds objectivity in assessment
• Allows partial work from home
• Controls missing information based on protocol
Remote Study
Performance
monitoring
• Controls the recruitment process

12. Value Proposition (cont.)
Risk Profiles of
Sites
• Guide on-site workload based on Risk Profiles
To-Do Expert
System
• Formalizes the knowledge & experience about
trial management
Keeping Risk
CAPA process
under control
• Rationalized RBM reports and alert
communications
• Total risk analysis audit for regulatory agencies
• Objective assessment of a risky situation &
possible consequence
Total Risk
Defense
Strategy
• Transparency of risk management of a trial
• Audit trail when risk was identified and what
was undertaken, by whom
• Final risk management report at the end of a
trial

13. Cyntegrity’s Services
Definition of
Key Risk
Indicators
• Risk indicators validation
• Programming of specialized risk indicators
• Objective assessment of site performance
Proof of
Protocol for a
Risk Adaptive
Approach
• Monitoring plans
• Study adaptive approach
Application of
RBM with
Automatic
System
EarlyBird®
• Needed software
• Needed hardware
• Needed process