top 5 warning signs your clinical trial is off track

Mark Shapiro, MBA, RACDirector, Clinical Solutions

Clinipace, Inc.

www.clinipace.com© 2003-2009 Clinipace, Inc. All Rights Reserved.

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www.clinipace.com© 2003-2009 Clinipace, Inc. All Rights Reserved. www.clinipace.com© 2003-2009 Clinipace, Inc. All Rights Reserved.

We already know

Thomson CenterWatch 2003, 2005 survey of sites in U.S.


Risk Management: A Four-Step ProcessRisk Management: A Four-Step Process

1. Risk Assessment and Analysis: Work with the Sponsor to agree on potential risks to the study across all study phases and then prioritize them in terms of importance

2. Risk Mitigation: Put in place processes or systems to proactively reduce the likelihood that identified risks become issues

3. Risk Measurement: Work with the Sponsor to agree on and implement measures necessary to assess risks and determine whether they have become issues

4. Risk Management: Define actions to be taken in response to those risks that become issues during the course of the study.

We define risks as potential events with a non-zero likelihood that could impact the timelines, cost, or quality of the study.

Recognizing warning signs that a trial is off track falls into the category of Risk Measurement

Risk Management Framework


Warning Signs to Look for…Warning Signs to Look for…

CRF, database, and planning activities are driven off of a synopsis or draft protocol

Protocol not approved in first cycle of IRB reviewPoor site compliance with regulatory document

submissionsPoor Investigators’ Meeting attendance

CRF, database, and planning activities are driven off of a synopsis or draft protocol

Protocol not approved in first cycle of IRB reviewPoor site compliance with regulatory document

submissionsPoor Investigators’ Meeting attendance

How to measure…How to measure…

Close contact with central IRB% of PI’s that attend the IMClose contact with central IRB% of PI’s that attend the IM

How to fix…How to fix…

Gather site feedback on the draft protocol

Target key central IRB sites during start-up

Gather site feedback on the draft protocol

Target key central IRB sites during start-up

Related ChallengesRelated Challenges

Slower than expected enrollment


Study Start-Up


Warning Signs to Look for…Warning Signs to Look for… Target enrollment rate does not match historic rates Fewer sites than expected show interest in participating in

the study Study coordinators raise questions or concerns about the

inclusion/exclusion criteria or schedule of assessments High screen-failure rate observed Poor awareness of the treatment standard-of-care and /or

competitive landscape (global and local)

Target enrollment rate does not match historic rates Fewer sites than expected show interest in participating in

the study Study coordinators raise questions or concerns about the

inclusion/exclusion criteria or schedule of assessments High screen-failure rate observed Poor awareness of the treatment standard-of-care and /or

competitive landscape (global and local)


Use technology to measure and monitor screening, enrollment, and screen failure rates

Reassess enrollment expectations at the PSV and IM

Use technology to measure and monitor screening, enrollment, and screen failure rates

Reassess enrollment expectations at the PSV and IM

How to fix…How to fix… Build enthusiasm for the

scientific aims of the study Focus on high-performing

sites Facilitate learning and

information-sharing across sites

Identify and activate back-up sites early

Build enthusiasm for the scientific aims of the study

Focus on high-performing sites

Facilitate learning and information-sharing across sites

Identify and activate back-up sites early

Related ChallengesRelated Challenges

First subject, first visit is delayed

First subject, first visit is delayed

Study Start-Up


Early Warning Signs to Look for…Early Warning Signs to Look for…

Breakdown of the Sponsor-CRO relationshipStudy monitoring is poorly aligned with site

enrollmentProtocol amendments requiredPass-through costs are greater than expectedEnrollment lags expectations

Breakdown of the Sponsor-CRO relationshipStudy monitoring is poorly aligned with site

enrollmentProtocol amendments requiredPass-through costs are greater than expectedEnrollment lags expectations

How to measure…How to measure…Availability of PM or other key team membersOn-line monitoring visit calendarAnalyze spending rates on invoices

Availability of PM or other key team membersOn-line monitoring visit calendarAnalyze spending rates on invoices

How to fix…How to fix… Start with a clear and

comprehensive Communication and Risk management plan

Use remote and just-in-time monitoring

Validate site cost expectations before setting trial budget

Start with a clear and comprehensive Communication and Risk management plan

Use remote and just-in-time monitoring

Validate site cost expectations before setting trial budget

Related Warning SignsRelated Warning SignsSlower than expected

enrollmentProject team turnover


Project team turnover

Study Operations



Historic turnover rateHistorical delays or challenges with the programRising starsAttitude and enthusiasm of the project teamAvailability of project team members

Historic turnover rateHistorical delays or challenges with the programRising starsAttitude and enthusiasm of the project teamAvailability of project team members


Ask about turnover rate and transition plansPay attention to attitude and availability

Ask about turnover rate and transition plansPay attention to attitude and availability

How to fix…How to fix…Start with a clearly

defined transition planFollow the

Communication and Issue Escalation Plan

Manage quality of life challenges

Start with a clearly defined transition plan

Follow the Communication and Issue Escalation Plan

Manage quality of life challenges

Related Warning SignsRelated Warning SignsData Quality

ChallengesTrial Cost Overruns

Data Quality Challenges

Trial Cost Overruns

Study Operations



Sites express concerns or have many questions about the protocol or schedule of assessments

Poor alignment of monitoring visits with site enrollment Inexperienced sites or monitorsHigh subject drop-out rateLag time for data entry at sitesHigh query rate (in general or around specific CRF fields)

Sites express concerns or have many questions about the protocol or schedule of assessments

Poor alignment of monitoring visits with site enrollment Inexperienced sites or monitorsHigh subject drop-out rateLag time for data entry at sitesHigh query rate (in general or around specific CRF fields)

How to measure…How to measure…Use technology to track questionsUse technology to measure data collection and drop-out

ratesMonitor query trends

Use technology to track questionsUse technology to measure data collection and drop-out

ratesMonitor query trends

How to fix…How to fix…

Maintain and FAQ starting from the PSV and IM through the study

Use experienced sites and monitors

Validate the protocol with the CRO and sites

Maintain and FAQ starting from the PSV and IM through the study

Use experienced sites and monitors

Validate the protocol with the CRO and sites

Related Warning SignsRelated Warning Signs

Project team turnoverProject team turnover

Study Operations


Q&A

Mark Shapiro, MBA, [email protected]

top 5 warning signs your clinical trial is off track

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