This document summarizes a webinar on streamlining data management for clinical trials. The webinar covered the need for streamlined approaches given rising drug development costs. It discussed areas for improving efficiencies, including using standards, a parallel approach, identifying key reviewers, and tailoring processes based on trial type (e.g. a "Premier Express" approach for small phase 1 trials). An example case study showed how streamlining tasks and performing work in parallel reduced timelines for developing case report forms, annotated case report forms, databases, and edit checks for a small phase 1 trial from 9 weeks to 5 weeks.

1. 2 0 1 1 FA L L B I O M E T R I C S W E B I N A R S E R I E S
Streamlining Data Management Start-up
Nov. 15, 2011 Presented by Cheryl Silva

2. Cheryl Silva
 Associate Director, Technical Operations
 Expertise in:
– CRF design
– Database development
– Application support
– Electronic data handling
– Report programming
 Programming/software development background
 Bachelor’s degree in Computer and Information
Science from the University of Massachusetts
2011 FALL BIOMETRICS WEBINAR SERIES

3. Today’s Topics
3
▪ Need for Streamlined Approach
▪ Areas for Efficiencies
– Standards
– Parallel approach
– Identifying key reviewers
– One size doesn’t fit all
▪ Summary
2011 FALL BIOMETRICS WEBINAR SERIES

4. Need for Streamlined Approach
In 2003, health economists in the US estimated the average cost
of bringing a drug to market at US$802 million. Today, those
Drug Approvals – From
costs are forecasted in the range of $1.3 to - $1.7 billion. Clinical
trials cost is one of the biggest expense categories for
Invention to Market…
biopharmaceutical companies.
The Industry Challenge:Year Trip
A 12-
• More than 80% of clinical trials experience delay
from one to six months costing pharmaceutical
companies upwards of $35,000 per day, per trial.
• Only 10% of trials are completed on time.
2011 FALL BIOMETRICS WEBINAR SERIES

5. Need for Streamlined Approach
In 2003, health economists in the US estimated the average cost
of bringing a drug to market at US$802 million. Today, those
costs are forecasted in the range of $1.3 to - $1.7 billion. Clinical
trials cost is one of the biggest expense categories for
biopharmaceutical companies.
The Industry Challenge:
• More than 80% of clinical trials experience delay
from one to six months costing pharmaceutical
companies upwards of $35,000 per day, per trial.
• Only 10% of trials are completed on time.
2011 FALL BIOMETRICS WEBINAR SERIES

6. Need for Streamlined Approach
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7. 2005 Survey
Factors that Could Best Prevent Future Delays
7
% “Best Prevent Future Delays”
50% 45%
42%
40% 37% 35% 34%
30%
20%
10%
0%
EDC Fewer More Money Standardized Sites Involved
Technologies Intermediaries for Patient CRFs Earlier in the
Recruitment Protocol
Process
Source: CenterWatch Survey of Investigative Sites in the U.S., 2005 (n=612)
Multiple responses offered
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8. Electronic Data Capture
8
Medidata Rave…
Improving efficiency
of study build and
life cycle
management
Electronic Data
Capture (EDC)…
expedite
time-to-market
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9. 2009 Survey
Factors that Could Best Prevent Future Delays
9
% “Best Prevent Future Delays”
50%
40%
31% 30% 29%
30% 27% 26%
20%
10%
0%
Fewer Streamlined EDC More Money Standardized
Intermediaries Contracting Technologies for Patient CRFs
and Budgeting Recruitment
Source: CenterWatch Survey of Investigative Sites in the U.S., 2009 (n=950)
Multiple responses offered
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10. Streamlining Study Start-up
10
Without a streamlined study start-up process, the
following efficiencies gained through the use of EDC are
diminished:
 Real time data entry/data availability
 Real time data cleaning
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11. Efficiencies
 Standards
 Parallel Approach
 Identifying Key Reviewers
 One size does not fit all
– Premier Express
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12. Standards
12
▪ Standard CRFs
▪ Global Library objects
▪ Standard Data Validation Plan (DVP) pre-populated
with Standard edit checks
▪ Different companies maintain different Standards
– Premier Research follows
Clinical Data Acquisition
Standards Harmonization
(CDASH) industry standards
▪ Important: Agreeing to Standards up front saves time
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13. Parallel Approach
13
Identify tasks that can be performed in parallel
Edit Check Edit Check
Start DVP
Programming Testing
Identify CRFs
Live Database
from Standards
Start Database Database
Study Training
Build Testing
Data Manager
Data Programmer
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14. Key Pieces to Parallel Approach
14
Resource Managing
Standard
Allocation and Timeline
Timelines
Management Shifts
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15. Parallel Approach
15
Perform Parallel Reviews
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16. Parallel Approach
16
Perform Parallel Reviews
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17. Identifying Key Reviewers
17
Identify key reviewers based on:
1) Deliverable
– Edit check specification will not necessarily have the same reviewers as Data
Entry Guidelines
– Create a table of deliverables and identify reviewers & approvers
Deliverable Reviewers/Approvers
Data Management Plan Project Manager, Lead Data Manager
Edit Check Specifications Lead Data Manager, Database Developer
Batch Data Load Specifications Database Developer, Clinical Programmer
Dataset Listings Lead Data Manager, Clinical Programmer
2) Role
– Example: Chief Operating Officer does not need to review CRFs
– Example: CRA does not need to review dataset specifications
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18. One size does not fit all
18
Different types of trials have different study start-up needs
Phase 3 Phase 1
Global Multicenter Single Center
Oncology Trial Pain Trial
Number of Sites 258 1
Number of Subjects 1200 48
Duration 3.5 years 4 months
Number of CRF page 60 unique pages 24 unique pages
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19. Premier Express
19
Premise:
▪ Process designed to meet the needs of small phase 1
pharmaceutical and device studies
▪ Timelines for these studies are short
Key components:
▪ Standard data collection pages
▪ Don’t need to collect and subsequently analyze more data
than necessary
– Standard single module edit checks
– Limited sponsor reviews of key documents to expedite
execution of trial
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20. Case Study
20
 DATA MANAGEMENT 45 days
 Mock eCRF Development 13 days
STANDARD 9 WEEK TIMELINE Mock eCRF Development & Internal Review 6 days
Sponsor v1.0 Review and Comments Provided 3 days
13 days for CRF development Mock eCRF v1.0 Updated Based on Sponsor Comments 1 day
Sponsor v2.0 Review and Comments Provided 2 days
Mock eCRF v2.0 Updated Based on Sponsor Comments 1 day
Sponsor Approval 0 days
 Annotated Case Report Form (aCRF) 11 days
aCRF Development & Internal Review 3 days
Sponsor v1.0 Review Comments Provided 3 days
11 days for aCRF development aCRF Updates Based on Sponsor Comments 1 day
Sponsor v2.0 Review Comments Provided 3 days
aCRF Updates Based on Sponsor Comments 1 day
Approval Annotated CRF 0 days
 Database Development 8 days
Database Developed 2 days
8 days for database development Database QC & DM Testing 4 days
Data Entry Screens Tested by Sponsor (UAT) – optional 2 days
Database Activation 0 days
 Edit Check Programming 13 days
Edit Checks Programmed 5 days
13 days for edit check development Data Management Testing 8 days
Edit Checks Activated 0 days
2011 FALL BIOMETRICS WEBINAR SERIES

21. Case Study
21
Phase 1 Single Center Pain Trial
Number of Sites 1
Number of Subjects 48
Duration 4 months
Number of CRF page 24 unique pages
 Goal: database and edit checks activated within 5 weeks
 Plan:
1) Use existing Premier Research CDASH Standard CRFs
2) Sponsor waived their review of CRFs and annotated CRFs
3) Limit internal CRFs and annotated CRFs reviews to relevant parties
and implement review meetings to streamline communication
4) Execute activities in parallel
2011 FALL BIOMETRICS WEBINAR SERIES

22. Case Study
22
 DATA MANAGEMENT 45 days
 Mock eCRF Development 13 days
ACCELERATED 5 WEEK TIMELINE Mock eCRF Development & Internal Review 6 days
Sponsor v1.0 Review and Comments Provided 3 days
4 days for CRF development Mock eCRF v1.0 Updated Based on Sponsor Comments 1 day
Sponsor v2.0 Review and Comments Provided 2 days
Mock eCRF v2.0 Updated Based on Sponsor Comments 1 day
Sponsor Approval 0 days
 Annotated Case Report Form (aCRF) 11 days
aCRF Development & Internal Review 3 days
Sponsor v1.0 Review Comments Provided 3 days
3 days for aCRF development aCRF Updates Based on Sponsor Comments 1 day
Sponsor v2.0 Review Comments Provided 3 days
aCRF Updates Based on Sponsor Comments 1 day
Approval Annotated CRF 0 days
 Database Development 8 days
Database Developed 2 days
7 days for database development Database QC & DM Testing 4 days
Data Entry Screens Tested by Sponsor (UAT) – optional 2 days
Database Activation 0 days
 Edit Check Programming 13 days
Edit Checks Programmed 5 days
11 days for edit check development Data Management Testing 8 days
Edit Checks Activated 0 days
2011 FALL BIOMETRICS WEBINAR SERIES

23. Case Study
23
 Mock eCRF Development 13 days
STANDARD Mock eCRF Development & Internal Review 6 days
Sponsor v1.0 Review and Comments Provided 3 days
13 days for CRF
development Mock eCRF v1.0 Updated Based on Sponsor Comments 1 day
Sponsor v2.0 Review and Comments Provided 2 days
Mock eCRF v2.0 Updated Based on Sponsor Comments 1 day
Sponsor Approval 0 days
Initial eCRF development and review reduced from 6 to 4 days by copying eCRFs Premier Research’s
standard pages. Sponsor leveraged Premier Research CDASH and study start-up expertise regarding the
look/feel of the data entry pages and the alignment of the data collection requirements with the protocol.
 Mock eCRF Development 13 days
4
ACCELERATED Mock eCRF Development & Internal Review 6 days
4
Sponsor v1.0 Review and Comments Provided 0
3 days
4 days for CRF
development Mock eCRF v1.0 Updated Based on Sponsor Comments 0 days
1 day
Sponsor v2.0 Review and Comments Provided 0
2 days
Mock eCRF v2.0 Updated Based on Sponsor Comments 0 days
1 day
Sponsor Approval 0 days
2011 FALL BIOMETRICS WEBINAR SERIES

24. Case Study
24
 DATA MANAGEMENT 36 days
 Mock eCRF Development 4 days
ACCELERATED 5 WEEK TIMELINE Mock eCRF Development & Internal Review 4 days
Sponsor v1.0 Review and Comments Provided 0 days
4 days for CRF development Mock eCRF v1.0 Updated Based on Sponsor Comments 0 days
Sponsor v2.0 Review and Comments Provided 0 days
Mock eCRF v2.0 Updated Based on Sponsor Comments 0 days
Sponsor Approval 0 days
 Annotated Case Report Form (aCRF) 11 days
aCRF Development & Internal Review 3 days
Sponsor v1.0 Review Comments Provided 3 days
3 days for aCRF development aCRF Updates Based on Sponsor Comments 1 day
Sponsor v2.0 Review Comments Provided 3 days
aCRF Updates Based on Sponsor Comments 1 day
Approval Annotated CRF 0 days
 Database Development 8 days
Database Developed 2 days
7 days for database development Database QC & DM Testing 4 days
Data Entry Screens Tested by Sponsor (UAT) – optional 2 days
Database Activation 0 days
 Edit Check Programming 13 days
Edit Checks Programmed 5 days
11 days for edit check development Data Management Testing 8 days
Edit Checks Activated 0 days
2011 FALL BIOMETRICS WEBINAR SERIES

25. Case Study
25
 Annotated Case Report Form (aCRF) 11 days
STANDARD aCRF Development & Internal Review 3 days
Sponsor v1.0 Review Comments Provided 3 days
11 days for aCRF
development aCRF Updates Based on Sponsor Comments 1 day
Sponsor v2.0 Review Comments Provided 3 days
aCRF Updates Based on Sponsor Comments 1 day
Approval Annotated CRF 0 days
Initial aCRF development and review remains the same since aCRF generation is usually standard. Sponsor
leveraged Premier Research CDASH and start-up expertise regarding the names of the database objects.
 Annotated Case Report Form (aCRF) 11 days
3
ACCELERATED aCRF Development & Internal Review 3 days
Sponsor v1.0 Review Comments Provided 0
3 days
3 days for aCRF
development aCRF Updates Based on Sponsor Comments 0 days
1 day
Sponsor v2.0 Review Comments Provided 0
3 days
aCRF Updates Based on Sponsor Comments 0 days
1 day
Approval Annotated CRF 0 days
2011 FALL BIOMETRICS WEBINAR SERIES

26. Case Study
26
 DATA MANAGEMENT 28 days
 Mock eCRF Development 4 days
ACCELERATED 5 WEEK TIMELINE Mock eCRF Development & Internal Review 4 days
Sponsor v1.0 Review and Comments Provided 0 days
4 days for CRF development Mock eCRF v1.0 Updated Based on Sponsor Comments 0 days
Sponsor v2.0 Review and Comments Provided 0 days
Mock eCRF v2.0 Updated Based on Sponsor Comments 0 days
Sponsor Approval 0 days
 Annotated Case Report Form (aCRF) 3 days
aCRF Development & Internal Review 3 days
Sponsor v1.0 Review Comments Provided 0 days
3 days for aCRF development aCRF Updates Based on Sponsor Comments 0 days
Sponsor v2.0 Review Comments Provided 0 days
aCRF Updates Based on Sponsor Comments 0 days
Approval Annotated CRF 0 days
 Database Development 8 days
Database Developed 2 days
7 days for database development Database QC & DM Testing 4 days
Data Entry Screens Tested by Sponsor (UAT) – optional 2 days
Database Activation 0 days
 Edit Check Programming 13 days
Edit Checks Programmed 5 days
11 days for edit check development Data Management Testing 8 days
Edit Checks Activated 0 days
2011 FALL BIOMETRICS WEBINAR SERIES

27. Case Study
27
STANDARD  Database Development 8 days
Database Developed 2 days
8 days for Database QC & DM Testing 4 days
database Data Entry Screens Tested by Sponsor (UAT) – optional 2 days
development
Database Activation 0 days
Because Standard CRF are used, database objects may be copied in from Standard Global Library. This
reduces initial development and QC time by 1 day. Sponsor UAT testing increases from 2 to 3 days because
this is the first time sponsor is seeing data entry screens.
ACCELERATED  Database Development 8 days
7
Database Developed 21days
day
7 days for Database QC & DM Testing 4 days
3
database
Data Entry Screens Tested by Sponsor (UAT) – optional 2 days
3
development
Database Activation 0 days
2011 FALL BIOMETRICS WEBINAR SERIES

28. Case Study
28
 DATA MANAGEMENT 27 days
 Mock eCRF Development 4 days
ACCELERATED 5 WEEK TIMELINE Mock eCRF Development & Internal Review 4 days
Sponsor v1.0 Review and Comments Provided 0 days
4 days for CRF development Mock eCRF v1.0 Updated Based on Sponsor Comments 0 days
Sponsor v2.0 Review and Comments Provided 0 days
Mock eCRF v2.0 Updated Based on Sponsor Comments 0 days
Sponsor Approval 0 days
 Annotated Case Report Form (aCRF) 3 days
aCRF Development & Internal Review 3 days
Sponsor v1.0 Review Comments Provided 0 days
3 days for aCRF development aCRF Updates Based on Sponsor Comments 0 days
Sponsor v2.0 Review Comments Provided 0 days
aCRF Updates Based on Sponsor Comments 0 days
Approval Annotated CRF 0 days
 Database Development 7 days
Database Developed 1 day
7 days for database development Database QC & DM Testing 3 days
Data Entry Screens Tested by Sponsor (UAT) – optional 3 days
Database Activation 0 days
 Edit Check Programming 13 days
Edit Checks Programmed 5 days
11 days for edit check development Data Management Testing 8 days
Edit Checks Activated 0 days
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29. Case Study
29
STANDARD  Edit Check Programming 13 days
Edit Checks Programmed 5 days
13 days for Data Management Testing 8 days
database
Edit Checks Activated 0 days
development
Because Standard database objects are used, edit checks may be copied in from Standard Global Library.
This reduces initial development and QC time by 1 day.
Note: The example used in this case study required more edit checks than usual because of the complicated
enrollment criteria. Typically, the use of Premier Express would nearly eliminate all programming time.
ACCELERATED  Edit Check Programming 13 days
11
Edit Checks Programmed 5 days
4
11 days for Data Management Testing 8 days
7
database
Edit Checks Activated 0 days
development
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30. Case Study
30
 DATA MANAGEMENT 25 days
 Mock eCRF Development 4 days
ACCELERATED 5 WEEK TIMELINE Mock eCRF Development & Internal Review 4 days
Sponsor v1.0 Review and Comments Provided 0 days
4 days for CRF development Mock eCRF v1.0 Updated Based on Sponsor Comments 0 days
Sponsor v2.0 Review and Comments Provided 0 days
Mock eCRF v2.0 Updated Based on Sponsor Comments 0 days
Sponsor Approval 0 days
 Annotated Case Report Form (aCRF) 3 days
aCRF Development & Internal Review 3 days
Sponsor v1.0 Review Comments Provided 0 days
3 days for aCRF development aCRF Updates Based on Sponsor Comments 0 days
Sponsor v2.0 Review Comments Provided 0 days
aCRF Updates Based on Sponsor Comments 0 days
Approval Annotated CRF 0 days
 Database Development 7 days
Database Developed 1 day
7 days for database development Database QC & DM Testing 3 days
Data Entry Screens Tested by Sponsor (UAT) – optional 3 days
Database Activation 0 days
 Edit Check Programming 11 days
Edit Checks Programmed 4 days
11 days for edit check development Data Management Testing 7 days
Edit Checks Activated 0 days
2011 FALL BIOMETRICS WEBINAR SERIES

31. Summary
 Time benefits gained from the use of EDC can
only be realized when an efficient DM
approach is used
 Efficiencies in study start-up can be gained
through the use of standards, advanced
planning, and tailoring the process to meet the
project needs
2011 FALL BIOMETRICS WEBINAR SERIES

32. Upcoming Webinars
32
Register at www.premier-research.com/webinars
▪ Strategies for Implementing CDISC
13 December at11:00 am EST
Speaker: Thomas Kalfas
Listen to past webinars:
▪ The Role of Data Monitoring Committees
Speaker: Ron Kershner, Ph.D.
▪ IVR/IWR…More than just Randomization
Speaker: Ryan Michaud
2011 FALL BIOMETRICS WEBINAR SERIES

33. Questions?
Cheryl Silva
Associate Director, Technical Operations
234 Copeland Street
Quincy, MA 02169
Telephone: 617.237.1120
cheryl.silva@premier-research.com
2011 FALL BIOMETRICS WEBINAR SERIES