How to Implement an
ePRO Strategy:
A Best Practice Guide
Frans Wald
Head Global Clinical Trial Support
Boehringer Ingelheim Pharma GmbH
.
26th Annual
EuroMeeting
25-27 March 2014
ACV, Vienna
Austria
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Authors of Best Practice Guide
Dr. Daniel Eek
PRO Senior Scientist
AstraZeneca R&D Molndal
Dr. Karoly Kulich
PRO Director
Novartis – Basel
Dr. Frans Wald
Head Global Clinical Trial Support
Boehringer Ingelheim Pharma GmbH & Co.KG
Martin Wurm
Head of eClinical Trial Services
Global Clinical Trial Support
Boehringer Ingelheim Pharma GmbH & Co. KG
3
Overview
• How ePRO/eCOA Changes Internal
Processes
• Advantages of Centralized
Knowledge
• How to Implement an ePRO
Strategy
4
Stakeholders for transition to
ePRO
• PRO Team / Health Economics
• Clinical Operations
• Biometrics, Programming, DM
• Regulatory / Quality Management
• Sourcing
• IT
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Some Advantages of ePRO
• Meets recommendations of regulatory
guidances for claims.
• Improves patient compliance with scheduled
completion of diaries.
• Reduces missing information
• Increases accuracy data with automatic
timestamps & prevents retrospective entry
• Designed so that patients cannot leave
incomplete items.
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Some Disadvantages to ePRO
• ePRO data collection may require a higher
initial cost compared with paper PRO.
• Trial teams have limited time to document
or capture knowledge or lessons learned
from (e)PRO trials.
• Trial setup with ePRO requires that all
data issues be resolved prior to FPI
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Differences when collecting PRO or ePRO
Data Endpoints
• Proof that each instrument is ‘fit for context of use’ if data
are submitted for a labeling claim
• New questionnaire validations and translations
• Diary translations
• Cognitive debriefs for existing paper PRO instruments
• IRB or EC approval for patient material
• Potential risk that the developer of a PRO tool will
request an equivalency study. Equivalency testing for
layout, patient acceptance and psychometric properties
can be costly and take up to a year.
• FDA guidelines
8
ePRO Requires a Change in
Processes and Personnel
9
Various Regulation Mandates
for ePRO
• FDA Guidance: PRO Measures
• EMA Reflection Paper
• EU respective government laws
• ICH Technical Requirements
for Registration of
Pharmaceuticals for Human
Use
10
Industry ePRO Standards &
Recommendations
• CDISC
• Critical Path Institute (C-Path)
• PRO Consortium
• Internat. Society for Pharmacoeconomics
and Outcomes Research (ISPOR)
11
Rules for Exchange of
Electronic Records
• eSource data governed by Guidances &
Regulations
• ePRO data are eSource data, meeting all
requirements
Additional Rules for Exchange of
Electronic Records
•
•
•
•
•
•
21 Code of Federal Regulations (CFR) Part 11
Organisation for Economic Co-operation and Development
EU Data Protection Directive
Health Insurance Portability and Accountability Act (HIPAA)
Act of the Protection of Personal Information (Japan)
Asia-Pacific Economic Cooperation framework mandate for personal data
protection
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4 Key process modifications
Paper PRO
ePRO
Data
 Paper diary translations
Collection  Paper diary duplication & shipping
 Site personnel and patient training,
 User acceptance testing of the ePRO device
 Software programming to include logical
branching, randomization and other devicelevel calculations.
 Specify Data Clarification Form (DCF)
Data
conditions and process
Managem
 Specify how entry errors will be managed
ent
 Determine the transcription process from
paper to the database
 Define source data, especially when
Data
someone completes a diary on behalf of a
Analysis
patient
 Determine when analysis can begin after
last patient out (LPO)
 Determine how trial data will be pooled
with other clinical data.
Reporting  Anticipate when reporting can begin
 Specify DCF conditions and process
 Specify electronic data transfer formats
 Clarify data transmission and transfer
frequencies.
 Define how often interim analysis will be
conducted to determine enrollment,
compliance and power achievements
 Determine how trial data will be pooled with
other clinical data.
 Train site and trial personnel on how to
access real-time data online
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FDA Roadmap Specifies Process
14
Advantages of a Centralized
Knowledge Center
Health
Economi
cs
Clinical
Ops
IT
• Global project team
dealing with ePRO &
eDevices
Regulato
• Sponsored by
ry
senior management
ePRO
Team
Biometry
Program
ming DM
Sourcing
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Quality
Mngt
Main Goals and Tasks
• Global single point of contact for all trial teams &
vendors together with key stakeholders
• Support all trial teams in managing the
ePRO/eDevices related tasks
Preparation
• Selection
of device &
vendor
• Prepare &
review
documents
• Logistics
• Training
Conduct
• Questions
• Software
Updates
• Issues
• Escalation
Close-out
• Database
lock
• Return of
Equipment
• Lessons
Learned
Main Goals and Tasks
• Save cost and time in implementing standards
 Build up ePRO/eDevices Working Groups for each
Therapeutic Area to create Company standards
 Standardize and implement processes and documents
together with working groups resulting in shorter
timelines and reduced complexity
• Create and maintain knowledge base and lessons learned
• Increased utilization of ePRO instead of paper
• Find innovative solutions for new requirements and
requests (e.g. FDA, special measurements in studies)
Therapeutic Area Team
• Functional sub teams formed for specific topics:
Data Management, Training Options,
Standardization of e.g Respiratory Documents
• Main Outcomes:
– Pre-selecting devices & preferred vendors
– Standardization of documents (User Acceptance
Testing, Data Management Plan, …)
– Adaptation and enhancement of eLearning from
Vendor
– Definition of KPIs and Governance & Escalation
Structure
– Start-Up Package for CMs
Experts Select Devices
• Screen is large enough to display entire question and
answers, to avoid possible scrolling bias.
• Screen is large enough in height and width to
accommodate translations, especially of voluminous
languages such as German
• Screen is bright and clear with legible text, numbers,
buttons and scales.
• The exact device selected will be available throughout
trial duration, in order to avoid mid-study delays with
cognitive debriefs.
• Device has sufficient memory to host all diaries and
questionnaires required of protocol.
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Experts Select Devices, based on Critical
Provider Requirements
Data Management
Data Security
Flexible Data Change
Process and Workflow?
Consistency checks
executed by provider?
Integration with other
eClinical
Systems?
Server Uptime
Number of Redundant
Servers
Does the Device perform
a Quality Check upon
Data Transfer?
Data Transfer options
SAS, SASII, ASCII, SDTM, ‘Normalized’ tables and Oracle Clinical® formats?
Device
Are purchase and lease
options available?
Global Transmissions
Management
Global Trial Experience
Type of transmission
options: 3G WiFi,
Internet, Analog
Number of Sites which
have used the vendor's
ePRO system
Is Logistics Management Are Regional Distribution
in-house or contracted?
Depots Available?
Transmission Metrics
Transmission experience
in a given country –
which option works best
Number of Languages
Number of Countries
which have been used in
which have used the
the vendor's ePRO
vendor's ePRO system –
system
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Additional Considerations
•
PRO/ePRO Questionnaires
–
•
Modifying a paper diary or questionnaire to ePRO
requires evidence to confirm the new instrument’s
adequacy
Vendor should provide an eDiary Design Tool
–
IRB and EC require screen shots or other similar
instrument representations.
•
Mixing ePRO devices – fine
•
Switching ePRO devices – disastrous!
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Some Recommendations
• Lead by a team, not a single individual
• Centralize the ePRO team
• Retain and archive lessons learned and
operational intelligence collected from ePRO
trials
• Establish PRO competence before implementing
ePRO process
• Enable ePRO to be the default mode of PRO
data collection
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Questions?
How to implement an ePRO Strategy: A Best Practices Guide
http://bit.ly/1adF1Cd
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