epharma day munich - rbm with eu clinical trials regulation

EPharma Day, Munich

11th of June 2015

Artem Andrianov, PhD, MBA

How to master the new EU Clinical Trials Regulation

with RbM?

Quality by Design Concept

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Desired Product Perform

ance

Product Design

Process Design

Process Perform

ance

Quality

by

Design

• Product Specifications• Product Quality Attributes• Process Parameters• Process Controls

• Continuous Improvement

• Product knowledge• Process understanding

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Duality of RbM definition: EMA vs FDA

RbM - is an important part of

a preventive clinical trial management.

RbM - is the adequate mix of strategies

including centralized and on-site monitoring

practices

„Both show the target, but do not describe the way“


Pharma Mega-Trends

•Go-global in pharma

•Cost pressure -> Outsourcing

•Cost pressure again

•Personalized medicine

•Diagnostic-accompanied medicine

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New EU Regulation

Overview

New EU Regulation does not take any direct reference on RbM

Both should produce data of enhanced quality where it really counts

RBM should be a tool in that process, but it isn’t the only one – QbD is essential to maximise the gains from our new clinical research environment

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Both have the same key principles: interest of subjects has the ultimate priority over all other interests.


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• Two primarystudy objectives

• Inclusion and exclusion criteria verification

Risk-adaptive Protocol

• KRIs & KPIs & KQIs

• ValidationRBM plan

• Risk Monitoring

• Risk Preventing and Reacting

Operative Risk

Management

RbM Components

How RbM works?

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Definition of Key Risk Indicators

Protocol for a Risk-Adaptive Approach

Site Monitoring Plans

• Which data points can be verified centrally?

• How decision algorithm is defined when data are outside the design space?

RBM in Clinical Trial

• Statistical monitoring

• Integration process

• Risk indicators validation

• Validation of the protocol


New Clinical Trial Regulations Key Principles

Transparency

• New publicly accessible EU clinical trials register

• Summary of the CT results must be published within one year

• Understandable outcomes should be published for layperson

• Clinical Study Reposts – publically available

Simplicity

• Streamlined application procedure

• Single set of documents

• Simplified reporting procedures

Speed-processing • Deadlines for the assessment of clinical trial application

Patient Safety• Involvement of the ethics committees in the assessment procedure

• More detailed Informed Consent requirements

Harmonization• Clinical trials conducted outside the EU, but submitted in an application

for marketing authorisation in the EU, they have to follow the new guideline

Data Quatliy • Data captured during a clinical trial must be trustworthy and robust.

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Here risk management can help

Risk Management For New Clinical Trial Regulation

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Data connection to EDC, CTMS and other clinical trial recording systems helps in applying the KRIs relevant for regulation

KRIs

Deadlines: reporting about

(S)EAs

Compliance with the protocol

Safety RecruitmentFraud &

sloppiness detection

Reliability and robustness of

the data generated


KRIs for patient’s safety

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Informed Consent signature time and rightness

Recruitment, appropriate population

AEs, and SAEs, safety under-reporting

Data quality and robustness of data (Key Quality Indicators)

Wrong accompanying therapies or absence of a therapy, when it should be the case

Pharma Mega-Trends

•Go-global in pharma

•Cost pressure -> Outsourcing

•Cost pressure again

•Personalized medicine

•Diagnostic-accompanied medicine

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Case Studies

Case Study 1: Control over the (S)AE underreporting

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Safety Risk over 60%

Lower Number of AEs for a site


Trail Details:• Sponsor: AstraZeneca• Area: Oncology Phase III, Randomised, Placebo-controlled• Double-blind Study for Prostate Cancer Patients. • 670 Patients • 253 Sites

Case Study 2: Low Performing Sites

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Low Performing Sites

Anomalies in Unscheduled Visits


Trail Details:• Sponsor: AstraZeneca• Area: Oncology Phase III, Randomised, Placebo-controlled• Double-blind Study for Prostate Cancer Patients. • 670 Patients • 253 Sites

Case Study 3: Low Data Quality

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Site with much data submitted (size of the bubble) and poor data quality.

“Data normality test” shows that data is not normal-distributed.


How Robust an Indicator?

Key Risk Indicator is effective only if it is:•Reliable

•Pro-active (so called “leading indicator”)

Alarm! + CAPA


Key ‘take-away’ messages

The new EU Clinical Trials Regulation:

underlines patient safety,

simplifies the trial registration process and

increases data transparency.

data captured during a clinical trial must be trustworthy and robust.

The controlling of the data robustness can be delegated to a data driven RbM

It is essential to start gaining experience already now – you gain an important competitive advantage.


Contact Us

Tel: +49 (0) 6192-470-113-50

Email: [email protected]

Web: www.cyntegrity.com


mailto:[email protected]

http://www.cyntegrity.com/

epharma day munich - rbm with eu clinical trials regulation

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