Post on 21-Jul-2015
Getting a Clinical Research Protocol Started
The CTSA Response
Daniel E Ford, MD, MPHVice Dean for Clinical Investigation
Director, Institute for Clinical and Translational ResearchJohns Hopkins School of Medicine
Current State
• Time to initiate studies longer for US than most countries
• Steps required to start study are increasing (ex, billing for services provided in clinical trial)
• Recent NCI analysis found that for cooperative group phase 3 trials time from original idea to activation of study was 808 days (481 distinct processes)
June 22-23, 2008
Enhancing Clinical Investigation by
Improved Management
A Workshop Convened by the
Clinical and Translational Science Award (CTSA) Consortium/
Regulatory Knowledge Workgroup/
Clinical Research Management Taskforce
Organizing Committee
• Teshia Johnson, MBA Yale
• Michael Joyner, MD Mayo• Robert Califf, MD Duke
• Daniel Ford, MD, MPH Johns Hopkins
• Daniel Rosenblum, MD NIH NCRR
Premeeting Survey
• Three surveys similar
to each of 24 CTSA institutions
– CTSA PI (representing researcher perspective)
– IRB Director– Research Administration (contracts) Director
PI Survey Results
• 4 Institutions post performance measures for IRB and contracting
• IRB barriers– Incomplete applications from research teams– Infrequent meetings of IRB or subcommittees– IRB committees too picky about wording
PI Survey Results
• Major barriers for contracting– Even if Master agreements in place,
they are not followed by companies
– Legal review too slow– Difficult negotiations related to
indemnification, publication rights and data transfer
PI Survey Results
• 84% contracting longer than IRB
• 5% IRB longer than contracting
• 11% equal time for both
• Where delays occur:– 36% sponsors– 48% academic centers
– 21% PIs and research teams
Research Administration Survey
• Huge variation in organizational structure
• 36% of staff have left in past three years
• 78% of contracts tracked electronically– 34% of those faculty can view status of
contracts
• 50% report not meeting with one sponsor in 2007 to discuss contracting
IRB Survey
• Average of 2025 protocols approved in 2007 (682 convened)
• Average of 18 staff– 50% turnover since 2005
• 50% of protocols tracked electronically
• 50% of institutions do not pay their IRB members
• 55% met with no sponsors/NIH in last year
Agenda for Workshop
• Stakeholder perspective on problem– Walter Koroshetz, MD NINDS– Nancy Trapp, Eli Lilly Sponsor
– Tony Perez, JD IRB– Gary Chadwick, PhD Alternative IRB– James Moran, JD Contracts– Sara Rockwell, PhD Faculty
Agenda for Workshop
• Discussion groups addressing specific questions
• Poster session where everyone could share best practices and recent quality improvement programs
Why do we need research study initiation performance measures?
• Perception of sponsors and research faculty we are inefficient
• No other accreditation organization has taken on this role– Association of Human Resource Protection Programs (AHRPP)– Office of Human Research Protections (OHRP/HHS)– Federal Drug Administration (FDA)
• Opportunity for “the doers” to be proactive and lead the way
Why do we need research study initiation performance measures?
• Measurement is the first step to understanding the process
• Same metrics across multiple academic sites allows comparisons and identification of best processes (ask for more resources if not performing as expected)
• Measurement of performance metrics tends to reduce variability
Why do we need research study initiation performance measures?
• Posting metrics for sponsors and public demonstrates responsibility and accountability
• Once we demonstrate accountability, can ask for same from sponsors and research teams
Challenges to Measuring Performance
• Selecting the right performance measures– Are study protocols included in the performance
measure representative or informative?– Are the performance measures easy to measure?– Can the performance measures be measured with
reliability?• Does the performance measure vary too much by type of
study to be informative? (pediatric vs. adult, first site versus 50th site)
• Do the performance measures provide hints about the process or what the path to improvement might be?
Challenges to Measuring Performance
• Is speed the only measure of performance? What about quality of IRB review? What about quality of a contract that is clear and covers multiple potential problems?
• Are there ways to “game” the performance measures?
First Performance Metric
• Duration in days from receipt of first “ready” study protocol/site agreement received to time both the clinical investigational site and sponsor have executed the agreement
Performance Metric Definitions
• What studies are included?– Multicenter clinical trials
• Easier to assign date when site was able to start study initiation/approval process
• Include all sponsors (NIH and commercial)
– Dates• 2007 chosen as most study protocols will have
had opportunity to be activated
Performance Metric Definitions
• When is start date?– Date agreement sent from sponsor– Date agreement is received– Research teams may not have recorded
this date
Performance Metric Definitions
• Time to executed site agreement– Total days or “business” days?– Is it date when one party signed agreement or
when all parties signed agreement?– Possible to “game” this time by signing agreements
quickly and then need multiple amendments to really have study ready to enroll participants
Performance Metric Definitions
• Days to execution of agreements – How to count protocols that never were
completed?– What about outliers?
– Report median or 90th percentile?– Report 25, 50 and 75 percentile?– Report percent of protocols that met
some performance standard
First Performance Metric
• Duration in days from receipt of first “ready” study protocol/site agreement received to time both the clinical investigational site and sponsor have executed the agreement
Days to Enrollment Ready by Percentiles
132 209 265 352 372
113164
196263
307
050
100150200250300350400
0.25 0.5 0.75 0.9 1
No. o
f Day
s
Commercial Funding - Days from protocol receipt to contract execution
Federal Funding - Days from protocol receipt to IRB approval
Days to Contract Execution by Percentiles (Start date when contract presented to Research Office)
919
28
53
143
0
20
40
60
80
100
120
140
160
25%
50%
75%
90%
100%
Number of Agreements Completed
Nu
mb
er
of
Da
ys
IRB Performance Metric
• Duration in days from PI receipt of protocol to site IRB approval- Measure protocol receipt to initial (department
or IRB) submission
- Measure protocol receipt to IRB submission complete
- Measure protocol receipt to first IRB review
IRB Performance Metric
50 Multi-center, Sponsored, Clinical Trials Submitted in 2007
0
77
106
123
157
0
20
40
60
80
100
120
140
160
180P
roto
col
rece
ive
d b
y si
te
Initi
al
IRB
/De
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on
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ple
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RB
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w
IRB
ap
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val
Num
ber
of D
ays
IRB Outcome Measures
50 Multi-center, Sponsored Clinical Trials submitted in 2007
7
14
29
02
0
5
10
15
20
25
30
35
Ap
pro
ved
at
first
me
etin
g
Mo
difi
catio
ns
req
uir
ed
at
first
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De
ferr
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at
first
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etin
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Dis
ap
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at
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Ave
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Nu
mb
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Stu
die
s
Insights from Workshop
• Valuable forum to bring together IRB and research administration professionals
• Need to consider the entire study initiation process
• Need to bring general counsels into the quality improvement process
• Agree that establishing metrics will aid in quality improvement
• Not certain if goal is to standardize study management across sites or maximize efficiency within each site with own solutions
Process For Implementing Study Initiation Metrics
Post Metrics on Performance on www.CTSAweb.org
Performance report on 2007 multi-center studies, due Sept 1st.
Report plan to CCOC
Present metrics, request comments from sites, general counsels at sites, NIH and others by Feb 1st
Review the recommendations from each task force and propose combined set of metrics by Jan 1st
CTSA Clinical Research Management Taskforce
Report data to CRM TF
3 CTSA institutions to volunteer to gather data on performance metrics
Contracts TF site – collect data on multi-center studies for itself and 4 other sites
Propose 3 core and 2 optional metrics by Nov 15th
Contracts Task Force
Report data to CRM TF
3 CTSA institutions to volunteer to gather data on performance metrics
IRB TF site – collect data on multi-center studies for itself and 4 other sites
Propose 3 core and 2 optional metrics by Nov 15th
IRB Task Force
Sept/10Sept/093/092/091/0912/0811/08Item/Month