This document summarizes a presentation on ensuring data quality in global clinical trials. It discusses deconstructing study protocols and plans to identify essential elements before initiating studies. Plans should be simplified and aligned across regions and partners. Study start-up is improved by engaging sites early and providing integrated training that simulates the trial process. An online community helps maintain relationships and information sharing with sites. The goal is to focus on critical data needs rather than planning excessively.

1. Data Quality Deconstructed:
Do more, plan less
Global Clinical Trials
14-Sep-2012 Boston
Eileen M. Daniel
Director, Clinical & Data Operations
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2. 15+ years ago
New York City
Spring 1997
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3. Today there is nothing new under the sun
… except maybe some clouds
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4. During this talk, I will
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remind us of fundamentals
provide facts about a global study
tell you where & why we liberally apply brakes
flashback to a deconstruction methodology
close with thoughts on site and study initiation
©2012 Endo Pharmaceuticals Inc. All rights reserved.
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5. stating the obvious
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6. We all know this
The clinical trials we sponsor are research studies.
– A study is conducted according to a well-defined study plan
– That well-defined study plan is the protocol
Clinical investigators are responsible for conducting studies in
accordance with the protocol.
We are obliged to oversee and keep sharp focus on:
– Protection of human subjects
– Integrity of study data
– Compliance with applicable regulations
To meet our oversight obligations we conspire to plan.
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7. the plans (sigh)
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8. The plans for a global phase 3 study
– 3.5 FTEs with global responsibility
study leader | data manager | study specialist | clinical information mgr
– 450 subjects recruited from 120 sites
North America, Europe, India
– 10 service partners including 4 CROs
– All study data flows in electronically from three sources
eCRF, central laboratory, IVRS
– 1 protocol, 1 playbook and 7 global plans
Bladder cancer is challenging enough. Starting up was hard to do.
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9. Starting up – forming our global study community
study
community
study community >600
+clinical investigators & team
study team >30
study team
clinical sub
team
clinical trial
manager
+partner project managers
clinical sub-team >10
trial manager
research scientist
statistician
data manager
project management
regulatory affairs
health economics
pharmacovigilance …
Alignment is possible so long as you manage the plans variables.
©2012 Endo Pharmaceuticals Inc. All rights reserved.
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10. Oh boy … the plans! I didn’t want to read any of them
– Loads of variables
– $75,000* total cost for one
– Had to tease out
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the redundant
the confounding
the conflicting
the work-inducing
– 90%** is NOT REGULATED
*I did not make this up
**I made this up
We needed a timeout!
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11. forcing a slowdown at startup
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12. ©2012 Endo Pharmaceuticals Inc. All rights reserved.
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13. Kick off meeting Study team preparation
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14. Attention here please
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15. pre-prep preparation… JDI
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16. The CI is not the only one waiting for a final protocol
Sometimes it is a game to see who can hold out the longest.
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17. And They’re Off!
Final protocol to FPI: 12 weeks
ICF
CRF
DMP
DRP
SAP
Safety Plan
IDMC Charter
Monitoring Plan
Escalation Plan
Communication Plan
Clinical Supplies Plan
File Management Plan
Medical Monitoring Plan
Sponsor Oversight Plan
Project Management Plan
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18. ©2012 Endo Pharmaceuticals Inc. All rights reserved.
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19. Hold up – deconstruct the protocol before inking any plans
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Dissect for data
Make an inventory
Tie-back to protocol objectives
Take out the WANTs, leave the NEEDs
Dispense with the notion of a CRF page
Identify a single point of origin for every item
Draw a map to illustrate how it flows end to end
Know how and where it will be presented in the study report
– Accept this is an iterative process and it will be revisited. This is okay.
Ask the questions no one else wants to, confront the risks early and often.
©2012 Endo Pharmaceuticals Inc. All rights reserved.
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20. Plans we find useful in a global, multi-regional study
protocol
–
the
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a 2-page
tells us at a glance where we have transferred
obligations, the names of the people working our study and which organization’s SOPs are being followed
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a PPT document with lots of white space called the
completed by our service partners
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the
tasks based on study risk analyses
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an
what, when, how and who without replication of content that should be sourced elsewhere
Sponsor Oversight Plan
playbook that documents the plays for the tasks
global monitoring plan that describes expectations for on-site and centralized monitoring
integrated data management & review plan that describes the
+ The most overlooked: the plan to share it all with our sites.
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21. site & study initiation
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22. New (?) approach to training
– Study Initiation Meeting
– No longer PI centric, no silo presentations
– Advance enlistment of trusted sites
– tell them they are coming along the way
– start them up early & invest too much time
– engage them in planning
– Integrated delivery of study information
– simulate screening a subject & processing through study
– Service & technology providers are team members
– Study team intends to learn as much as they teach
First be armed with real-world qualitative experience, then go large.
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23. Build a sense of community & keep it online
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24. final thought