William Gluck, PhD VP, DATATRAK Clinical and Consulting Services

April 11, 2013

Mitigating Risk in Clinical Studies

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Introduction

William ‘Bill’ Gluck, Ph.D, DATATRAK International, Inc. @DATATRAKinc

Bill Gluck joined DATATRAK International in October 2010 as VP of DATATRAK’s Clinical and Consulting Services (DCCS). Dr. Gluck has more than 28 years of experience in the pharmaceutical and biotechnology industries and has diversified experience in clinical trial management

systems and electronic data capture.

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Agenda

•  Risk in Clinical Studies –  Definitions –  Identifying Risk in Clinical Trials

•  Study Set-Up and Initiation •  Study Conduct and Optimization

•  Leveraging Technology to Mitigate Risk •  Thoughts on the Future –  Virtual Trials –  Technology Driven Drug Development (TD3™)

•  Wrap-Up

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Risk in Clinical Studies

Risk1 A probability or threat of damage, injury, liability, loss, or any other negative occurrence that is caused by external or internal vulnerabilities, and that may be avoided through preemptive action Risk Mitigation2 A systematic reduction in the extent of exposure to a risk and/or the likelihood of its occurrence 1http://en.wikipedia.org/wiki/Risk

2http://www.businessdictionary.com/definition/risk-mitigation.html

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Identifying Risk In Clinical Studies

►  Study Set-Up and Initiation •  Study Protocol •  Qualification, Training, Experience of all Study Personnel •  Recruitment •  Informed Consent

►  Study Conduct and Optimization •  Protocol Deviations (inclusive of eligibility criteria) •  Drug Accountability •  Data Collection and Data Quality

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Study Set-Up and Initiation Leveraging Technology

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Study Protocol

Risk •  Study protocol is not well defined •  Complex •  Risk assessments and plans are not adequate •  Amendments and Mid-Study Changes

Mitigation •  Use of CDISC standards

– Protocol and Study/Trial Design Model •  Adaptive study design planning •  Risk-based Approach planning •  Electronic Data Collection (EDC)

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Adaptive Study Design Study design that allows: •  Modification of pre-defined aspects of a study •  Interim reviews of accumulating study data •  No affect on the validity and integrity of the trial

Adaptive design requires: •  Multiple stages •  Access to accumulated study data •  Apply the following rules (one or more) at interim reviews:

–  Allocation Rule –  Sampling Rule –  Stopping Rule –  Decision Rule

At any interim data review subsequent stages of the study can be redesigned taking into account all available data

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Risk-Based Approach to Monitoring Draft guidance – released August 2011 ►  FDA is clear that onsite visits are not always necessary and that

“centralized monitoring” may be preferred ►  Factors to consider when developing any type of monitoring plan

•  Complexity of study design •  Types of study endpoints •  Clinical complexity of study population •  Geography •  Relative experience of the clinical investigator and of the sponsor with the

investigator •  Electronic data capture

–  Metrics generation –  Site quality assessments

•  Relative safety of the investigational product •  Stage of the study •  Quantity of data

►  Potential time and money savings as well as increased data quality

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Qualification, Training, Experience

Risk •  Lack of experience •  Lack of essential documentation/records •  Medical records inadequately maintained

Mitigation •  Clinical Trial Management System (CTMS) •  Electronic Trial Master File (eTMF) •  EDC and/or e-Training Records

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Recruitment

Risk •  Identification of sites/patients •  Delays in recruitment/enrollment

– Due to recruitment of qualified participants – Due to site issues/quality

Mitigation •  Electronic Health Records •  Social Media •  EDC

– Patient data reviews – Metrics reporting

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Informed Consent

Risk •  Patient confidentiality and protection •  Adequately informed of study risks

Mitigation •  Standardization •  Use of multi-media •  Electronic Informed Consent (virtual studies)

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Study Conduct and Optimization Leveraging Technology

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Protocol Deviations

Risk •  Inclusion/Exclusion criteria •  Procedural deviations from the study protocol •  Enforcement of stopping rules/dose modification rules

Mitigation •  Electronic health records •  EDC

– Risk-based Approach to monitoring – Edit check specifications – Metrics reporting

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Drug Accountability

Risk •  Proper drug assignments •  Site accountability •  Dose management

Mitigation •  EDC

– Randomization – Drug inventory management – Metrics reporting

•  Electronic Reported Patient Outcomes (ePRO)

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Data Collection and Quality

Risk •  Site issues

– Data quality – high query rates – Staff turn-over

•  Patient diary data collection – incomplete data Mitigation •  EDC

– Risk-based Approach to monitoring – Metrics reporting – eTraining

•  ePRO

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Future Thoughts on the

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Virtual Studies

Combines process and technology to streamline the conduct of a study leveraging:

Protocol definitions and process SOP’s Electronic informed consent eTraining eSource EDC - Metrics reporting - Data import/export

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Technology Driven Drug Development (TD3™)

Patient-focused to improve patient adherence and safety as well as clinical outcomes More than a virtual trial, TD3™ is a holistic approach that leverages technology-based processes:

Address study needs Evaluate viability of drug pipeline Reallocate focus and resources

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WRAP-UP

Mitigating risk depends upon the identification of risks and the proactive planning to address points of risk during the clinical study Technology provides multiple tools to assist in assessing and mitigating risk The future is now – virtual trials and TD3™

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William Gluck, Ph.D. VP, DATATRAK Clinical and Consulting Services

DATATRAK International, Inc. Phone: 919-651-0222 Cell: 919-522-9681

E-Mail: Bill.Gluck@datatrak.net