August 20, 2014

eSource: What You Need to Know

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Your Speakers► Maura Bearden

• Maura is a graduate of the University of North Carolina at Chapel Hill and has been with DATATRAK in a variety of Clinical Data Management roles since 2012. Ms. Bearden’s expertise is in the streamlining of study start-up tactics, data management and customer service.

► Bill Gluck, Ph.D.• Dr. Gluck has over 30 years of expertise in clinical

research, with experience in sponsors, CROs, and with DATATRAK in a variety of roles. Dr. Gluck is also the Program Director for the Clinical Trials Research and Medical Product Safety/Pharmacoviligance programs at Durham Technical Community College. Dr. Gluck earned his Bachelor of Science Degree at the University of Scranton and Master and Ph.D. degrees from North Dakota State University.

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Agenda► Key Dates in Time: eSource► Overview of the Guidance Document on

Electronic Source Data in Clinical Investigations

► Why eSource?► Practical Applications – eSource: A CDM’s

Tale of Three Studies• Challenges of eSource Studies• Benefits of eSource Studies • Future of eSource

► Summary

Dr. Bill GluckVice President Clinical Knowledge

DATATRAK International

eSource: Guidance Overview

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Genesis of eSource: Key Dates in Time

► 1968 – LL Weed, New England Journal of Medicine 278:593-600

► 1980’s-present – Evolution of IRT, EDC, ePRO/eCOA technologies

► 1997 – Regulatory definitions begin to evolve• CDISC and an industry-led standardization

movement begin► September 2013 – Guidance for Industry

on Electronic Source Data in Clinical Investigations

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Guidance Document Addresses the Following

► Identification and specification of authorized source data originators

► Creation of data element identifiers to facilitate examination of the audit trail by sponsors, FDA, and other authorized parties

► Ways to capture source data into the eCRF using either manual or electronic methods

► Clinical investigator(s) responsibilities with respect to reviewing and retaining electronic data

► Use and description of computerized systems in clinical investigations

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eSource studies pertain to clinical trials where direct data entry into an electronic data capture system (EDC) is used in contrast to paper source studies where data are transcribed from a paper source into EDC.

Simply put (from the Guidance Document): “Electronic source data are data initially

recorded in electronic format.”

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Data Capture: Electronic Source Data Origination

► List of authorized source data originators should be developed and maintained by the sponsor and made available at each clinical site

► Examples of Data Originators:• Clinical investigator(s) and delegated staff• Clinical investigation subjects or their legally

authorized representatives• Consulting services• Medical devices• Electronic Health Records• Automated laboratory reporting systems• Other technology

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Data Capture: Source Data Capture, Data Element Identifiers, Modifications and Corrections, and Use of Data Quality

Checks► Source Data Capture

• Direct entry of data into the eCRF• Automatic transmission of data directly into the eCRF• Transcription of data from paper or electronic sources

to the eCRF• Direct transmission of data from the EHR to the eCRF• Transmission of data from PRO instruments to the

eCRF► Data Element Identifiers► Modifications and Corrections► Use of electronic prompts, flags, data quality

checks in the eCRF

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Data Review

► Clinical Investigators• Clinical Investigator(s) review and electronic

signature• Data exempt from investigator(s) review

► Modifications and Corrections During Review of the eCRF

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Retention of Records by Clinical Investigator(s)

► Retain control of the records• Completed and signed eCRF• Certified copy of the eCRF

► Be able to provide inspectors with access to the records that serve as electronic source data

► When transcription from paper occurs – the paper is the source and must be retained

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Data Access► Viewing Data

• Sponsors, CROs DSMBs and other authorized personal can view data before and after the clinical investigator has signed the completed eCRF– Allow for early detection of study-related

problems– Missing data– Data Discrepancies

► CDMP should list individuals with authorized access to the eCRF

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Use and Description of Computerized Systems

► Adequate controls must be in place► Note: determination of whether a computer

system is suitable may not be under the control of the clinical investigator or sponsor (EHRs for example) – see 45 CRF Part 170

► Documentation – if computerized system are to be used• Protocol/CDMP/Investigational plan• Description of security measures employed to

protect the data• Description/Diagram of the electronic data flow

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Why eSource?

► Companies are reluctant to move away from paper-based source documentation• It is very familiar and is today’s standard• It is well documented and has a clear audit trail• It has well documented security measures

► eSource• Higher data integrity = Streamlined Data

Review Process• Real-time accessibility

Maura BeardenClinical Data Manager

DATATRAK International

Practical ApplicationseSource: A CDM’s Tale of Three Studies

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eSource Case Studies

► Three Different eSource Studies ► Study 1:

• Phase 2, 160 subjects and 24 sites► Study 2:

• Phase 3, 400 subjects and 31 sites► Study 3:

• Phase 2, 210 subjects and 20 sites

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eSource Case Studies

►Analysis of three studies provides the following information:• Challenges of eSource Studies • Benefits of eSource Studies • Future of eSource

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Challenges of eSource Studies

► Workflow process between monitoring and data management

► Protocol-Specific system checks ► FDA Guidelines pertaining to data

originator elements for transcribed assessments

► Site Compliance of FDA Guidance of electronic source data

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Challenge of Workflow Process

►Workflow process between monitoring and data management • Study: Cross-comparison of all

three studies • Problem: How to document the

review between monitors and data management

►Solution: Additional data review flag

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Challenges of Protocol-Specific Checks

► Protocol-Specific System Checks• Study: Progression of all three studies • Problem: Number of protocol-specific

system checks► Solution: Identification of integral

protocol checks, help prompts and additional electronic case report forms (eCRFs)

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Challenges of FDA Guidelines

► FDA Guidelines pertaining to data originator elements for transcribed assessments • Study: Study 3• Problem: Coordinator entering information

into eCRF that is being read off by PI and the conflict with the data originator in EDC.

► Solution: additional review fields on eCRF that correspond to authorized data originator

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Challenges of FDA Guidance

► Site Compliance of FDA Guidance of electronic source data • Study: Study 1 • Problem: Sites writing study information

on paper► Solution: Note-to-File regarding paper

sources and retraining of site

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Benefits of eSource Studies

► Higher Data Integrity ► Real-Time Data Availability ► Decreased Time for Data

Management Review

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Higher Data Integrity Benefit

► Higher Data Integrity• No queries needed to correct

transcription errors between paper source and EDC

• Protocol-specific edit checks in the system and eCRF prompts prevent subjects who are not qualified from being randomized in the study

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Real-Time Data Availability Benefit

► Real-Time Data Availability• Allows for all information to be available

at any time• Reduce review time querying site to

enter information• Allows for real-time reports with all

available data

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Decreased Time for Data Mngt Review

► Decreased Time for Data Management Review• Reduced number of confirmation queries • Limits data management review to

cross-checks and traditional data management reviews

• Remote monitoring (increased importance)

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The Future of eSource

► Familiarity and optimization of start-up and workflow process of eSource studies • Familiarity and optimization can be seen

in an analysis of study 2 and study 3. –Decreased study deployment time –Distinct data review responsibilities

for data managers and monitors –Streamlining user errors

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Conclusions

► eSource has been recognized as an accepted means of capturing clinical data during clinical investigations by the FDA

► The FDA has provided guidance to industry for its implementation and use

► Case studies demonstrate the benefits of eSource trials:• Higher data integrity• Real-Time accessibility• Streamlined Data Management Review Time

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Questions

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Contact Information► Maura Bearden

• Maura.Bearden@DATATRAK.com ► Bill Gluck, Ph.D.

• Bill.Gluck@DATATRAK.com► General Questions about DATATRAK

• Dorothy.Radke@DATATRAK.com ► Find Us Online

• www.DATATRAK.com• http://www.slideshare.net/DATATRAK • @DATATRAKinc on Twitter• https://

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