Transcript Slide 1

How a Large CRO Has Implemented
and Benefitted from CDISC Standards
Amy Caison & Jhelum Naik, PPD
Challenges of Data Standards
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Implementing Data Standards: A challenging
task
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For CROs
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Vast and ever increasing
Constantly evolving
Sometimes ambiguous
Continuous training
Every client and their expectations are different
Standards provide a common language
Enable greater focus on the science and less on mundane
data tasks
Organizational standards can support the implementation
of SDTM data standards at each step of the study lifecycle
Data Standards: Carrot and Stick
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Carrot
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Regulatory submissions that
are easily interpreted,
understood, and navigated
by reviewers leading to
quicker decisions
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Cost-benefit analysis by
Gartner (2009) found
greatest return on
investment from standards
achieved from use of
standards throughout the
lifecycle of a study
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Enable efficiencies to
accomplish more work
faster at reduce cost
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Stick
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Forthcoming: Statutory
authority to reject nonconforming submissions
(PDUFA V)
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Retrospective application of
standards often results in
greater cost than collecting
standardized data from the
beginning of a project
Evolution of Standards Implementation
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In the beginning: non-SDTM standards 
simple mapping
Implementation of early versions of SDTM as
required by sponsors: bespoke programming
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Laborious, inefficient
Development of internal standards for uniform
implementation of SDTM across studies
Generation of tools to support uniform
implementation
Maturation of Standards Implementation
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Increase in client requests for SDTM
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Explosion of engagement with standards
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Each client has its own interpretation  drives flexibility in
tools and processes
Emergence of client-specific standards experts from the
larger pool of CDISC experts
SMEs
Subteams targeting specific tools or processes
Involvement in public review cycles
Active membership on standards committees and
involvement with standards working groups
PPD’s Use of CDISC: Motivation and Benefits
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PPD’s motivation is the same as for the CDISC organization:
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Improve time, quality and costs
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Allow easier integration of data
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Assist regulatory reviewers
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Shorten the time to get products to the market
CDISC was also chosen as PPD’s global standards because:
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There was a recognition that regulators would formally request CDISC in the
future
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Many of PPD’s clients were also starting to implement CDISC
PPD has been one of the early adopters which has meant that
investment has been made upfront, the benefits though are that
we have . . .
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Developed our experience
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Had time to develop tools to get the job done efficiently
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Had time to proactively prepare for future standard releases
Implementation
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Translation of CDISC industry standards by
expert groups
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Development of tools and processes to support
implementation
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Enable ease of use/adoption by project teams at all phases
of a study lifecycle
Includes organizational standards and implementation
guidance
Ensure adequate and timely project team
support and issue/question resolution
Ensure tools/processes are reviewed and
updated as needed when standards evolve
Implementation of CDISC
PPD Expert Groups
Feedback and Questions
Industry
Standards
PPD Expert
Groups
Organizational
Study
Industry
Standards
Clinical
Trial
Standards
Team
Dissemination and Support
Implementation of CDISC
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Steering Committee
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Cross functional committee
Responsible for:
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Creation and dissemination of
CDISC information at PPD
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Ensuring PPD is current
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Identification of key focus
areas
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Oversight for expert groups
and all PPD CDISC activities
PPD Expert Groups
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Expert Groups (with
relevant subteams) in
place:
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SDTM
ADaM
eCRTs
aCRF
Validation
Implementation of CDISC
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Development of utilities
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SDTM macro suite
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eCRT Utility
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Extensive use of templates (e.g., CRFs, ADaM, mapping specs, etc.)
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Data visualizations and dashboards
Expert groups support teams
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Tools & Processes
Global training for all Biostatistics & Programming staff
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Face-to-face
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WebEx Recordings
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Mentoring on projects
Support lines for each expert group for rapid issue resolution
All committees and groups have a responsibility to stay
current:
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Flag need for utility or material updates
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Continue to enhance and develop all utilities and material
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Share knowledge across company
Implementation of CDISC
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Utilities, Templates, & Tools
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Effort to do as much as we can with automated tools without losing the
flexibility being a CRO requires
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Emphasis is on application of core principles with room for study-specific
adaptation if needed
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Example: SDTM spec creation tool
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Creates a spec based on the data that includes the standard SDTM version-specific variables in each
domain
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Can programmatically substitute standard SDTM version-specific variables with client-specific
variables for each domain
Modular components, strive to avoid the “black-box”
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Tools & Processes
Programmers have the flexibility to apply only that which is needed/useful for any given
study
The standards provide the scaffolding which can be adapted to fit the study
design
Benefits
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Facilitates training and resource deployment
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Learn the standards, tools, and you can work on any study
for any client who uses CDISC-based standards
Dialects of standards
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We may all speak the same language, just somewhat different
versions of that same language
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“British English” v. “American English”
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Myth of “Standard English” = myth of “Standard SDTM”
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“Standard SDTM” v. “xSDTM” v. “ySDTM” v. “zSDTM”
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Allows for focus on differences, not the totality of each standard
Less of a learning curve, client to client
Enables focus on content, big picture, rather than minutiae
of technical standards application
Benefits
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Standards facilitate quality
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Required, expected, and permissible variable attributes
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easily/quickly identify data or programming issues
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Required SDTM variables with missing values obviously point to
an issue
OpenCDISC validator can enhance independent validation
and improve quality
Familiarity with standards  issue investigation can be
quickly focused and typical known causes can be quickly
explored
Benefits
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More efficient work processes
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Tools, utilities, and templates can automate many tedious,
time consuming tasks
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Creating hyperlinks in eCRTs
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Setting variable attributes in SDTM
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Developing specs
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Copying specs from one study to another similar study
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Applying client standards structures
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creating common/typical table shells (particularly safety)
Benefits
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Ensure precision, uniform implementation, and
quicker development
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Macros which perform common/standard functions across
datasets
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Creating supplemental qualifier datasets
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Implementing standard algorithms (e.g., xxSEQ, xxDY,
xxSTDY) where a fixed algorithm can be applied to multiple
domains
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Applying labels
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Ordering variables within a domain
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Assigning variable lengths
Benefits
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Project Management Trilemma: “Fast, Cheap,
Good – pick any 2” is the standard line
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You can pick all 3 with mature implementation of data
standards
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Can do more work with fewer resources in shorter periods of
time without sacrificing quality if standards are utilized
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Template programs and/or macros for ADaM and TLFs can be
developed that make use of expected variable names
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Increases the power of copy-over efficiencies
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Can undertake projects which would not have been possible
prior to data standards
If repeatability is planned for, greater and
greater efficiencies can be realized
Case Study: Multi-Study Program
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Four long-term Phase III studies with staggered
enrollments (with respect to each study)
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Similar protocols, estimated 2% difference across studies
Standards applies to all phases of the project lifecycle
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Use of similar vendors providing standardized data structures
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Identical CRF setup (except for protocol-specific differences)
Staggered start  lessons learned are relevant to latter
studies enabling course corrections to improve
performance
Case Study: Multi-Study Program
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Standards facilitate client communication and
understanding
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Standards at all stages increase efficiencies
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Common language
Improved communication and understanding between the
CRO and the sponsor
Consistent CRFs across protocols
Vendor data transfer specifications
SDTM standards
Enabled significant efficiencies for following studies after
initial development
Case Study: Multi-Study Program
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Standards can positively affect resource
utilization
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Two programmers were assigned to lead four studies
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Never more than 3 support programmers at any given time
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Reliance on standards meant quicker implementation by experienced
staff
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Net reduction in total number of individuals working on such a large
and complex multi-protocol program
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Issues from one study and their resolutions were easily transferred
to other studies since communication is more efficient in smaller
teams
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Sponsor teams were similarly small and consistent
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Results in a collaborative, cohesive team that worked well together
Case Study: Multi-Study Program
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Standards apply to processes as well
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All four studies had critical interim locks which were backto-back
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Study 1 lock + 30 days = study 2 lock, etc.
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Team faced challenges during first lock
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Rapidly generated lessons learned document
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Communicated issues through team
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Safeguards enacted across other studies
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Remaining 3 studies enjoyed lock/turn-around in record time
Case Study: Multi-Study Program
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Benefits
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Client reception
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2 additional projects awarded outside of the program
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Strong performance would not have been possible without
leveraging of standards throughout the project
Subsequent out-of-program projects benefitted
significantly from multi-study program
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Easy to program since standards were still used
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Significant team experience and familiarity ensured success
Increased client trust
Continued strong performance resulted in bolus of
additional awards from this client
Case Study: Fast & Furious
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100+ to 70+ safety and efficacy tables
supporting academic conference submissions
and publications, depending on protocol
Repeats on multiple protocols
Short notice, short turn-around
Development of standard shells
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Standard ADaM specs
Program & validation copy-over efficiencies: ADaM &
Tables
4 deliveries of different protocols in 6 months
Enables concurrent development, streamlined revision
Case Study: Fast & Furious
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Repeat project implementation then becomes:
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Copy shells/specs
Grab new data (SDTM)
Do an initial run of the ADaM to see what, if anything falls
out
Generally minor tweaks to address any data-driven issues
Run of table programs/validations to see baseline status
Generally minor tweaks to address any data-driven issues
Senior review
Delivery, often ahead of timelines
All possible because of data standards
Impact of Standards Proliferation
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Resource/timeline constraints determined to be
not related to any standards-oriented task
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Business-oriented details
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Budget and contract approval
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Receipt of client materials
Resource availability for senior and statistical review
Efficiencies are not unlimited; standards can only do so
much
Impact of Standards Proliferation
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Broad-based standards increasing capacities
for CROs more complex and numerous studies
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Results in greater project management requirements
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Ensure consistent standards implementation
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Coordinate resources
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Manage budgets and client communications
Leads to changing roles/responsibilities for programmers
and statisticians
Summary
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Evolution and maturation of standards
Implementation
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Benefits
Case studies
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Long-term, multi-protocol comprehensive program
Targeted post hoc analyses, repeated across multiple
protocols
Impact of standards
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Expert Groups (main driver)
Tools & Processes
Still a limit to efficiencies
Change in roles and responsibilities
Questions?
Copyright, 2014 by Pharmaceutical Product Development, LLC ("PPD"). This
Copyright, 2012 by Pharmaceutical Product Development, LLC ("PPD").
presentation, including the information contained herein and any associated
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