Restructuring the National Cancer Clinical Trials Research Enterprise

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Restructuring the National Cancer
Clinical Trials Research Enterprise

CTSA Clinical Research Management Workshop

• Sheila A. Prindiville, MD, MPH
• Coordinating Center for Clinical Trials
• National Cancer Institute
• June 22, 2009

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Clinical Trials Working Group

• Proposed 22 initiatives designed to support a
  transparent clinical trials enterprise that
  integrates the individually strong components of
  the current system into a cross-disciplinary,
  scientifically-driven, cooperative research effort

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CTWG Restructuring Initiatives

• Prioritization/Scientific Quality
• Involve all stakeholders in design and
  prioritization of clinical trials that address
  the most important questions, using the tools of
  modern cancer biology
• Coordination
• Standardization
• Operational Efficiency
• Enterprise-Wide/Integrated Management

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Components of NCIs Clinical Trials System

• Cooperative Groups
• Community Clinical Oncology Programs
• Early Drug Development Program of the
  Investigational Drug Branch
• Cancer Centers
• Specialized Programs of Research Excellence
  (SPOREs)
• Program Project and Investigator Initiated Grants

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Scientific Steering Committee (SSC) System

• Members are leading cancer experts and advocates
  from outside the Institute as well as NCI senior
  investigators who meet regularly to
• increase the transparency and openness of the
  trial design and prioritization process
• enhance patient advocate and community oncologist
  involvement in clinical trial design and
  prioritization
• convene Clinical Trials Planning Meetings to
  identify critical questions, unmet needs, and
  prioritize key strategies.
• Leverage current Intergroup, Cooperative Group,
  SPORE, and Cancer Center structures by
• increasing information exchange at an early stage
  of trial development
• increasing the efficiency of clinical trial
  collaboration
• reducing trial redundancy (phase II and phase
  III)
• developing, evaluating, and prioritizing concepts
  for phase III and large phase II clinical trials.

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Scientific Steering Committee (SSC) System

• Investigational Drug Steering Committee (IDSC)
  for strategic input to NCI for the
  prioritization of phase I and II trials for new
  agents
• Disease-Specific Scientific Steering Committees
  (SSCs) for prioritization of phase III trials
  and selected phase II studies
• Symptom Management and Health-Related Quality of
  Life Steering Committee (SxQOL) for symptom
  management trials and patient reported outcomes
  expertise
• Patient Advocate Steering Committee (PASC) to
  share best practices for advocates across the
  SSCs and ensure concept evaluation considers the
  patient community

http//restructuringtrials.cancer.gov/steering/ove
rview
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CTWG Restructuring Initiatives

• Prioritization/Scientific Quality
• Coordination
• Coordinate clinical trials research through
  data sharing and providing incentives for
  collaboration
• Standardization
• Standardize informatics infrastructure and
  clinical research tools and evaluate the
  feasibility of common clinical trials agreement
  language
• Operational Efficiency
• Enterprise-Wide/Integrated Management

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• START clauses Standard Terms of Agreement for
  Research Trials

• Collaborative project with Life Sciences
  Consortium of the CEO Roundtable, Cancer
  Centers, and Cooperative Groups to developed
  common language as starting point for
  negotiations
• Project Rationale
• Negotiation of clinical trials agreements is a
  key barrier to timely initiation of trials
• Perception that negotiated agreements contain
  clauses reflecting common key agreement concepts
• Perception that reaching common ground for each
  agreement requires unnecessary duplication of
  effort that delays trial initiation

www.ceoroundtableoncancer.org
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Project Methods

• Involved legal and business representatives 17
  Life Science Consortium company and 26 Cancer
  Center members
• Obtained copies of 78 clinical trials agreements
  from participating organizations (49 redacted
  final negotiated agreements and 29 templates)
• Agreements included company-sponsored and
  investigator initiated trials
• Identified key clauses through discussions with
  legal and business representatives intellectual
  property, study data, publication rights, subject
  injury, confidentiality, indemnification,
  biological samples

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Project Methods cont.

• Identified 45 concepts in the 7 key clauses
• Captured the exact language that embodied these
  concepts in the 78 agreements
• Organized agreement language into categories
  representing embodied concept
• Analyzed results for similarities and differences
  in key concepts across final negotiated
  agreements and templates

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Project Findings

• Final negotiated agreements showed greater than
• 67 convergence on the vast majority of
  concepts analyzed
• Developed common language with input from legal
  and business participants
• Language is a starting point for negotiations
• Toolkit at http//ccct.nci.nih.gov
• Biological clauses and terms for Cooperative
  Group studies under development

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CTWG Restructuring Initiatives

• Prioritization/Scientific Quality
• Coordination
• Standardization
• Operational Efficiency
• Use resources most efficiently through
  improved cost-effectiveness and accrual rates,
  and more rapid trial initiation
• Enterprise-Wide/Integrated Management

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Operational Efficiency Initiative

• Identify the institutional barriers that
  prolong the time from concept approval to accrual
  of the first patient

Dilts, D. M. et al. J Clin Oncol 244553-4557
2006
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Total Processes to Open a Cooperative Group Study
Comprehensive Cancer Center Processes
Cooperative Group Processes
Median 784 to 808 days Range 435-1604 days
Median 116 to 252 days Range 21-836 days
Depending Upon Site, based on the Phase III
trials studied JCO 2009 27 (11)
1761-66 Clinical Cancer Research 2008 14(11)
3427-33
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Process Steps for Opening aPhase III Cooperative
Group Study
Process Step Counts
The process steps reported only show one loop
in the process. Actual development frequently
includes multiple loops
JCO 2009 27 (11) 1761-66
17
Actual Accrual Per Trial RangesComprehensive
Cancer Centers
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Operational Efficiency Initiative

• Identify the institutional barriers that
  prolong the time from concept approval to accrual
  of the first patient, and develop solutions for
  overcoming these barriers

Dilts, D. M. et al. J Clin Oncol 244553-4557
2006
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Operational Efficiency Working Group

• Charged by the NCIs Clinical Trials and
  Translational Research Advisory Committee (CTAC)
  to recommend strategies for reducing the time for
  activation of NCI-supported clinical trials
• Co-Chairs Gabriel Hortobagyi, MD (MDACC) and
  James Doroshow, DCTD, NCI
• 63 members representing the broad oncology
  community

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OEWG Mission

• Phase I Develop strategies and implementation
  tactics for reducing the time for initiation of
  Cooperative Group and Cancer Center trials
• Reduce study activation time by at least 50
• Optimize NCI, sponsor, and investigator
  interactions to reduce delays
• Phase II Develop strategies and implementation
  tactics for reducing the time for completion of
  Cooperative Group and Cancer Center trials
• Increase the percentage of studies successful in
  reaching accrual target
• Assure timely completion of studies

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OEWG Trial Activation Situations

• Cooperative Group Phase II and III Trials
• Cooperative Group Investigational Drug Branch
  (IDB) Trials
• Cancer Centers Investigator-Initiated Trials
• Cancer Centers Cooperative Group Phase II and
  Phase III Trials
• Cancer Centers Investigational Drug Branch
  (IDB) Trials

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Topics Outside OEWG Purview

• Industry sponsored trials
• OHRP regulated issues (i.e., consent forms)
• CMS coverage determinations
• State laws and requirements
• Congressional funding mandates

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OEWG Progress

• For Cancer Centers and Cooperative Groups there
  is
• Agreement on the components of the trial
  activation process to be examined
• Agreement that timelines for opening all of the
  clinical trial types must be reduced by about 50
• Agreement on existing barriers to speedy trial
  activation
• Agreement that to substantively improve trial
  activation timelines will require major changes
  in every component of the system

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OEWG Next Steps Timeline

• Refine and prioritize recommendations
• Develop implementation plans for prioritized
  recommendations
• Next OEWG Meeting - September 16-17
• Prepare report by end of 2009

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Integrated Management
Extramural Clinical Trials Community
Clinical Trials and Translational Research
Advisory Committee (CTAC)
Coordinating Center for Clinical Trials (CCCT)
NCI Director
Clinical and Translational Research Operations
Committee (CTROC)
Divisions, Centers, and Offices
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• CCCT Staff Deborah Jaffe, Ray Petryshyn,
  LeeAnn Jensen, Steve Krosnick, Jean Lynn, Anna
  Levy, Sarah Fabian
• START clauses
• Judy Hautala and Dale Shoemaker from Science
  Technology Policy Institute (STPI)
• Hogan and Hartson
• Legal, business, and tech transfer staff from
  academic medical centers, cooperative groups, and
  industry

Acknowledgement
http//ccct.nci.nih.gov