- eSource refers to directly capturing clinical trial data electronically at its source rather than transcribing from paper. The FDA has issued guidance on eSource. - Three case studies of eSource clinical trials found that it led to higher data integrity, real-time data accessibility, and more streamlined data review compared to paper. However, defining protocol-specific checks and ensuring compliance with FDA guidelines on data originators were challenges. - With optimization of workflows and familiarity over time, the benefits of eSource are realized through decreased study initiation times and impacts on remote monitoring.

1. May 5, 2015
William Gluck, PhD, VP Clinical Knowledge
Program Director CTRA and MSP Programs - Durham Technical
Community College
eSOURCE: Data Capture Simplified –
Uncover Time and Cost Saving
Possibilities

2. Agenda
1. Streamlining Data Capture in Clinical Trials
2. eSource Guidance Overview
3. Practical Applications – A Tale of Three Studies

3. Indulge Me – A Brief Walk Down
Memory Lane

4. Ah…the good old days…..

5. The Dawn of Remote Data Entry…..
and Dial-up

6. Electronic Data Capture = Change!!

7. Today…….
► Technology seems to advance faster than we
can keep up
► EDC has been accepted industry-wide
• Success driven by technology and process
optimization
► We can still improve…..optimize…..build the
better mousetrap!

8. How Do We Optimize Data
Capture?
Start at the Source

9. eSource: Guidance Overview

10. Conceptually - What is eSource?
Simply put (from the Guidance Document):
“Electronic source data are data initially recorded
in electronic format.”
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.

11. 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

12. Associated Guidance
Documents/Regulations
► FDA Guidance Document: Computerized
Systems Used in Clinical Investigations
► FDA Regulations on Electronic Records and
Electronic Signatures (see 21 CFR Part 11)

13. Definitions
► Electronic Record: any combination of text,
graphics, data, audio, pictorial, or any other
information represented in digital form that is
created, modified, maintained, archived,
retrieved, or distributed by a computer system
(21 CFR 11(.3(b)(6))
An eCRF is an example of an electronic record
► Source Data: all information in original records
and certified copies of original records of clinical
findings, observations, or other activities in a
clinical investigation used for reconstructing and
evaluating the investigation ( 21 CFR 312.62(b),
ICH E6)

14. Why eSource? – Potential benefits
Capturing data via eSource and transmitting it to
the eCRF should:
• Eliminate unnecessary duplication of data
• Reduce transcription errors
• Encourage entering source data at a subject visit
• Eliminate transcription of source data prior to eCRF
data entry
• Facilitate remote monitoring of data
• Promote real time access for data review
• Facilitate the collection of accurate and compete data

15. Data Capture:
Electronic Source Data Origination
► Security and Integrity: 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

16. What are We Capturing?
Data element – represents the smallest unit of
observation captured for a subject in a clinical
investigation

17. 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 EMRs/EHRs
to the eCRF
• Transmission of data from PRO instruments
to the eCRF

18. Data Element Identifiers, Modifications
and Corrections, and Use of Data Quality
Checks
► Data Element Identifiers
• Originators of the data element
• Date and time of the element
• Clinical investigation subjects to which the element
belongs
► Modifications and Corrections
► Use of electronic prompts, flags, data quality
checks in the eCRF

19. 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

20. 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

21. 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

22. 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 systems are to
be used
• Protocol/CDMP/Investigational plan
• Description of security measures employed to protect
the data
• Description/Diagram of the electronic data flow

23. Practical Application of the
Guidance

24. 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

25. 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

26. eSource Case Studies
The three studies provided insights
into:
1. Challenges initiating eSource Studies
2. Benefits realized from the eSource
Studies
3. A view of the future of eSource

27. Challenges of the eSource Studies
► Workflow process at the site and between
monitoring and data management groups
► Defining protocol-specific system checks
► Understanding and ensuring compliance to the
FDA guidelines pertaining to data originator
elements for transcribed assessments
► Training the site staffs and monitors to ensure
compliance to the guidance

28. Challenges of Workflow Process
Workflow process at the sites and
between monitoring and data
management
• Study: Cross-comparison of all three
studies
• Problem #1: How to adapt site
workflows for eSource data capture
• Solution #1: Comprehensive review of
site practices and workflow and taking a
holistic approach to defining a ‘whole-
study’ an educational and workflow

29. Challenges of Workflow Process
Workflow process at the sites and
between monitoring and data
management
• Study: Cross-comparison of all three
studies
• Problem #2: How to document the
review between monitors and data
management
• Solution #2: Modify the EDC application

30. Challenges of Protocol-Specific
Checks
Defining 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)

31. 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

32. 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

33. Realized Benefits of eSource
Studies
► Higher Data Integrity (fewer auto and manual
queries)
► Real-Time Data Availability (rapid entry and
access)
► Increased Throughput at All Levels for Data
Review

34. Some Comments on the Future of
eSource
►Similar to the history of EDC
• eSource requires a learning curve
• With familiarity and optimization of workflows, study
initiation time decreases and study benefits become
realized
►Not all studies are optimized for eSource….yet
►Impacts Remote Monitoring and RBM
►EMR/EHR’s will continue to impact eSource
studies

35. Conclusions
1. eSource has been recognized as an accepted
means of capturing clinical data during clinical
investigations by the FDA
2. The FDA has provided guidance to industry for
its implementation and use
3. Case studies demonstrate the benefits of
incorporating eSource as part of the data
collection/capture plan:
• Higher data integrity
• Real-Time accessibility
• Streamlined Data Review and Accessibility

36. Questions