Getting a Clinical Research Protocol Started The CTSA Response

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Getting a Clinical Research Protocol Started The
CTSA Response

• Daniel E Ford, MD, MPH
• Vice Dean for Clinical Investigation
• Director, Institute for Clinical and
  Translational Research
• Johns Hopkins School of Medicine

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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)

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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

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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

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Premeeting Survey

• Three surveys similar
• to each of 24 CTSA institutions
• CTSA PI (representing researcher perspective)
• IRB Director
• Research Administration (contracts) Director

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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

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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

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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

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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

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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

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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

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Agenda for Workshop

• Discussion groups addressing specific questions
• Poster session where everyone could share best
  practices and recent quality improvement programs

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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

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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

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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

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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?

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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?

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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

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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

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Performance Metric Definitions

• When is start date?
• Date agreement sent from sponsor
• Date agreement is received
• Research teams may not have recorded this date

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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

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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

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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

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Days to Contract Execution by Percentiles (Start
date when contract presented to Research Office)
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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

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IRB Performance Metric
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IRB Outcome Measures
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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

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Process For Implementing Study Initiation Metrics