Cyntegrity, 2016

Artem AndrianovCEO Cyntegrity

LIFE DATA INTEGRITY

RBM - the Light SideWays of Trial Optimization

Application of Data-driven

Risk-based Monitoring

“May the force be with you”

(Master Yoda)

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 VisitsReduced Monitoring

Traditional:

Clinical Sites

Monitor (CRA)

On-Site Visits

Internal and External Risks

Internal Risks

Company

External Risks

4

Alarm! + CAPA

Right Actions in Right Time

Cost of Outsourcing by Function

Major cost-saving potential

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.”*

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].

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

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

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

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

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