In the course of any clinical trial, there are risks associated with specific activities and tasks. This webinar will highlight some of these key risk areas and provide guidance on combining technology with best practices to help mitigate risks.

1. Mitigating Risk in Clinical Studies
William Gluck, PhD
VP, DATATRAK Clinical and Consulting Services
April 11, 2013

2. 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.
Confidential – 2

3. 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
Confidential – 3

4. 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
Confidential – 4

5. 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
Confidential – 5

6. Leveraging Technology
Study Set-Up and Initiation
Confidential – 6

7. 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)
Confidential – 7

8. 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
Confidential – 8

9. 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
Confidential – 9

10. 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
Confidential – 10

11. 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
Confidential – 11

12. Informed Consent
Risk
• Patient confidentiality and protection
• Adequately informed of study risks
Mitigation
• Standardization
• Use of multi-media
• Electronic Informed Consent (virtual studies)
Confidential – 12

13. Leveraging Technology
Study Conduct and Optimization
Confidential – 13

14. 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
Confidential – 14

15. Drug Accountability
Risk
• Proper drug assignments
• Site accountability
• Dose management
Mitigation
• EDC
– Randomization
– Drug inventory management
– Metrics reporting
• Electronic Reported Patient Outcomes (ePRO)
Confidential – 15

16. 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
Confidential – 16

17. Thoughts on the
Future
Confidential – 17

18. 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
Confidential – 18

19. 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
Confidential – 19

20. 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™
Confidential – 20

21. William Gluck, Ph.D.
VP, D ATATRAK Clinical and Consulting Services
D ATATRAK International, Inc.
Phone: 919-651-0222
Cell: 919-522-9681
E-Mail: Bill.Gluck@datatrak.net
Confidential –