implementing risk-based monitoring: a cro ......intrinsic risks maturity of safety profile phase of...

Confidential – For Internal Use Only

IMPLEMENTING RISK-BASED MONITORING: A CRO PERSPECTIVE

Ben Dudley, Executive Director Alliance Management, Covance Inc.

3rd Annual Clinical Trials Oversight SummitBoston, 2 June 2014


Topics Covered

2

RBM Process Implementation

The RBM Landscape, Drivers and Barriers

Implementation Learnings

Accessing RBM Benefits

2


Significant Conversion to RBM Expected

3

RBM will become the new normalSource: Industry interviews commissioned by Covance. * Note: Not a quantitative forecast

Current use of RBM solutions

Expected use of RBM solution in the next 10 years*

Expected use of RBM solution in the next 5 years*

Regulatory mandate

Development cost increases

RBM process maturation

Increased quality expectations

Traditional Monitoring ApproachesRBM


RBM: What Is It?

4

ID Critical Data/

Processes

ID Critical Data/

Processes

Risk Identification

Risk Identification

Primary Prevention

Primary Prevention

Active Mitigation

Active Mitigation

Quality Surveillance

Quality Surveillance

Identification and Repair

Identification and Repair

AdaptationAdaptation

Holistic; proactive; preventive; dynamic; iterative RBM is a logical next step to enhance efficiency and quality

4

• Holistically identifies risk of failure

• Designs monitoring approaches to

prevent or mitigate risk

• Differentiates critical vs. non-critical

• Delivers fit for purpose quality –

flexible to study and regulatory need

• End to end trial conduct

transformation

• An extension to smart study design


What Might Be Slowing Adoption of RBM?

5

6%

10%

28%

32%

34%

34%

34%

38%

46%

0% 10% 20% 30% 40% 50%

Other*

Risk/reward for RBM not sufficient

Convincing senior management of benefits of RBM

Increased risk

Lack of internal knowledge/expertise to implement RBM

Identification of risk associated with clinical trial

Greater cost

Inability of CRO to rapidly adapt to changing needs

Maintaining sufficient quality

What are the biggest challenges with implementing RBM? (Select top 3)

Source: Covance commissioned RBM study, 2013

More than regulatory questions holding back RBM


RBM Process Implementation

6

1ProtocolDesign

2Risk

Assessment

4Performance

Analytics

Feedback throughout study

3Monitoring

Plan

• Starts with designing out risk: protocol is the blueprint for quality• Start with the end in mind – reliable data withstanding Agency scrutiny

5Monitoring Interventions

6Issue

Resolution


Identify Critical Data / Processes

Protocol Quality by Design

Risk-based Site Selection

Proactive Risk Identification & Mitigation

Patient safety, data integrity & regulatory compliance

Intervention & Adaptation

Risk Factor Analytics

Demonstrated ‘State of Control’

Centralized Data Surveillance

Study Delivery

RBM Process Implementation, cont.

RBM Plan

Study Planning

7


Translating Risk into Action

8

Appropriate risk management requires a broad range of tools

Examples Management Approaches

Intrinsic risks

Maturity of safety profilePhase of development

Adjusted average site visit intervalAdjusted average SDV levelProportion remote/on site

Design risks

Clarity of protocolPrimary endpoint approachFit vs. standard of care

Quality by design improvementsCentral data surveillanceSupplementary training (site/CRA)

In-Flight Risks

Site experienceStaff turnoverAdverse event reporting levels

Adjusted site-specific intervention levelsTurnover management and training plansIssue management plans

Confidential – For Internal Use Only9

• Study/Program level focus

• Robust RBM solution a differentiator (+ or –)

• Impetus to develop

• Readiness to invest

• Operational excellence and process innovation in our DNA

• Critical need for flexibility and adaptability – Sponsor agnostic

SPONSOR CRO

Sponsor and CRO Perspectives

• Compound level focus, integrates with TPP

• Drivers for change vary

• Executive urgency for improved efficiency

• Functional conservatism and variable silos to overcome

• Opportunities to leverage CRO partners

9


Clinical Operations

StatisticsMedicalData Management

Data Management

Medical

Fit for Purpose Throughout the Continuum

Protocol Design

CRF Design Monitoring Data

CleaningMedical Review

Statistical Review

10

Start with the end in mind


• Quality of critical data & processes enhanced through preferential focus

• Cost saving is a consequence of monitoring what matters

• Focus on Quality by Design and Risk, not SDV reduction

• Areas reduced are not critical from an outcome perspective

Functional View Holistic View

Overcoming Functional Barriers

• “RBM is all about clinical cost reduction”

• “Quality will suffer on variables not monitored” – risk prevention not considered

• “There is nothing wrong with how we’ve done things before”

• ‘Burning platform’ challenge is only for Clinical Operations

Focused change management

11


Implementation Learnings

• Variable needs and priorities• Tailored solution needed, consistent but flexible

Sponsor

• Managing monitor support expectations• Expectation-setting and alternative methodologies

Site

• Resource management• Change management• Access to information

Monitors

1212


Experiences from Implementation

13

• Ph III Pivotal Study• Reduced SDV• Targeted RMV

strategy• NDA/MAA approved

Example #2

• Cardiovascular outcomes study

• Full RBM Design• tSDV implemented• Ongoing, enrolling

Example #1

• Partner portfolio• ‘Fit-for-purpose’

monitoring• Tailored RMV/SDV• Multiple TA studies

Example #3

13


RBM Value Hierarchy

Protocol simplificationQuality-by-designRisk-based site selectionSystematic mitigationCentralized data surveillanceRisk-targeted on-site review

14

QUALTY

EFF I CI

ENCY

14

Ultimate aim – de-risking development


Impact of Efficiencies in Clinical Monitoring

15

Study Complexity

Cos

t/Effi

cien

cy v

s. T

radi

tiona

l Mon

itorin

g*

*Relates to clinical monitoring activities, not full study costs. Covance internal data


• Fit for purpose quality

• Alignment with regulators

• Demonstrated state of control

• Timely delivery

• Improved efficiency

SPONSOR PRIORITIES CRO PRIORITIES

Mutually Beneficial Implementation

RBM can transform risks into returns• Effective, adaptive resources allocated targeting maximum impact and value

• Proactive planning and focus on primary quality and state of control

• Efficiency gains a consequence of fitness-for-purpose

• Fit for purpose quality

• Alignment with regulators

• Demonstrated state of control

• Timely delivery

• Improved efficiency

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For more information, visit www.covance.com/RBM

implementing risk-based monitoring: a cro ......intrinsic risks maturity of safety profile phase of...

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