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A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program (2010)

Chapter: Appendix A: Previous and Ongoing Analyses Undertaken by NCI

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Suggested Citation:"Appendix A: Previous and Ongoing Analyses Undertaken by NCI." Institute of Medicine. 2010. A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. Washington, DC: The National Academies Press. doi: 10.17226/12879.
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Appendix A
Previous and Ongoing Analyses Undertaken by NCI

In the 50 years of its existence, the Cooperative Group Program has advanced the treatment of cancer and the conduct of clinical research. Despite these successes, the Cooperative Group Program has continued to face a number of challenges that threaten its effectiveness. To further explore the challenges and opportunities confronting the Cooperative Groups, multiple evaluations of the Program have been conducted. Two of the most recent reviews of the Cooperative Group Program include the Armitage report (1997) and a review by the Clinical Trials Working Group (CTWG) in 2005. As a result of the CTWG report, the National Cancer Institute (NCI) established the Operational Efficiency Working Group (OEWG) to provide recommendations for improving the time from concept approval to enrolling patients on a clinical trial. In addition to these specific recommendations aimed at the Cooperative Group Program, the Program has also been influenced by other working group recommendations, including the Translational Research Working Group (TRWG) report recommendations.

REVIEWS OF THE COOPERATIVE GROUP PROGRAM

Armitage Report

In 1996, the NCI director and the chair of the Extramural Board of Scientific Advisors commissioned an external review of the Cooperative Group Program in response to concerns that the clinical trials portfolio had become increasingly inefficient and unresponsive to evolving needs.

Suggested Citation:"Appendix A: Previous and Ongoing Analyses Undertaken by NCI." Institute of Medicine. 2010. A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. Washington, DC: The National Academies Press. doi: 10.17226/12879.
×

The Clinical Trials Review Group was asked to recommend changes to the current system that would (1) take advantage of the most promising opportunities in therapy and diagnosis; (2) prioritize the most important research questions so that they can be explored in the fastest possible time; (3) improve the organization, funding, review, and cooperation in the Cooperative Group Program; and (4) attract both patients and researchers to participate in clinical trials.

The review committee met six times over an 11-month period and included experts from academic research institutions, cancer centers, community oncology practices, cancer patient advocacy groups, and the National Institutes of Health. The committee released its findings, known as the Armitage report, after its chair, James Armitage, in 1997 (NCI, 1997). The report made the recommendations regarding review, funding, design, oversight, and administration of the NCI clinical trials system. A subsequent implementation committee report was completed in 1998.

Clinical Trials Working Group Report

In 2004, the NCI director established the CTWG to advise the National Cancer Advisory Board on the development, conduct, infrastructure, support, and coordination of cancer clinical trials across NCI. The CTWG was asked to develop recommendations to (1) optimize the NCI-supported clinical trials system by improving coordination and research infrastructure, (2) remove institutional and regulatory barriers that inhibit collaboration in clinical trials research, and (3) envision how clinical trials should use the tools of contemporary bioinformatics and molecular medicine.

The review committee conducted 7 face-to-face meetings and 10 group conference calls over a 16-month period and included experts from academic research institutions, community oncology practices, the pharmaceutical and biotechnology industries, cancer patient advocacy groups, NCI, the Food and Drug Administration (FDA), and the Centers for Medicare & Medicaid Services (CMS). The committee released its findings in 2005 (NCI, 2005b).

The committee proposed 22 recommendations to achieve four major goals for designing a more efficient national system for clinical trials conducted or supported by NCI, as follows: (1) better coordination, (2) prioritization based on solid science and the needs of patients, (3) standardized tools and procedures, and (4) improved operational efficiency (NCI, 2005b).

Recommendations

While the Armitage report had a broader focus than the CTWG report, including a focus on issues such as organization, prioritization,

Suggested Citation:"Appendix A: Previous and Ongoing Analyses Undertaken by NCI." Institute of Medicine. 2010. A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. Washington, DC: The National Academies Press. doi: 10.17226/12879.
×

participation, and funding, the CTWG report was more narrowly focused and emphasized coordination, collaboration, and the adoption of new technologies (Box A-1). Table A-1 lists the recommendations of both the Armitage and the CTWG reports, divided into several categories: data collection, standardization, and management; cooperation; process improvement; organizational and structural improvement; accrual; funding; and

BOX A-1

Comparison of the Armitage and Clinical Trials Working Group Committee Charges

  • Armitage Report (1997)

    • Is the organization of the Cooperative Group Program (number, membership, trials portfolio) best serving the needs of the field?

    • How can the program ensure that the most promising clinical research opportunities and therapeutic questions are identified and addressed in the fastest possible time?

    • How can the program be organized to

      • effectively deal with increasing pressures to steer patients away from academic medical centers,

      • enhance laboratory-to-clinic and clinic-to-laboratory information,

      • ensure optimal peer review of Cooperative Group trials,

      • optimize links between industry and the Cooperative Group Program to maximize program productivity, and

      • effectively oversee and support the clinical trials program?

    • What funding mechanisms would provide the most research progress in the clinical trials program?

    • What is the best relationship between the clinical trials program and other research programs of NCI?

    • What options exist to ensure the continued training of clinical researchers?

    • What are the incentives/disincentives for participating in clinical trials and how can NCI ensure that clinical trials are available to all segments of the population?

  • Clinical Trials Working Group (2005)

    • The CTWG was charged with developing recommendations and an implementation plan to optimize the NCI-supported clinical trials system by

      • improving coordination and research infrastructure,

      • removing institutional and regulatory barriers that inhibit collaboration in clinical trials research, and

      • envisioning how clinical trials should be conducted by using the tools of contemporary bioinformatics and molecular medicine.

SOURCES: NCI, 1997, 2005b.

Suggested Citation:"Appendix A: Previous and Ongoing Analyses Undertaken by NCI." Institute of Medicine. 2010. A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. Washington, DC: The National Academies Press. doi: 10.17226/12879.
×

TABLE A-1 Comparison of Prior Recommendations for the NCI Cooperative Group Program

 

Armitage Report

Clinical Trials Working Group

Data collection, standardization, and management

  • Cooperative Groups and cancer centers should have access to all relevant electronic databases and should be primary participants in the development and testing of the new NCI informatics system.

    • Data collection should be uniform among the groups:

    • Use the same protocol guidelines,

    • Simplify the eligibility criteria,

    • Standardize study endpoints,

    • Develop a common algorithm for protocol development,

    • Use the same common data collection forms,

    • Develop common toxicity criteria,

    • Develop common biostatistical principles,

    • Create a simplified common adverse drug reaction and adverse event reaction reporting system, and

    • Simplify informed-consent documents.

  • NCI should enlist industry and the clinical trial and patient communities to work with FDA to develop uniform standards and reporting requirements for clinical trials.

  • Entry criteria for all studies need to be simplified and broadened: a range, rather than absolute, set of parameters should be considered.

  • Data collection should be reduced to only data pertinent to study endpoints and patient safety.

  • Large, uncomplicated trials of common cancers with minimal data requirements and accrual goals large enough to see definitive treatment differences should be part of the Program’s portfolio.

  • Tissue samples and other clinical data from intergroup trials should be stored and maintained.

  • Create a comprehensive database that contains regularly updated information on all NCI-funded clinical trials.

  • Create a national cancer clinical trials information technology infrastructure, fully interoperable with NCI’s Cancer Bioinformatics Grid, to improve the cost-effectiveness and comparability of results across trials and sites.

  • Develop a standards-setting process for measurement, analysis, and reporting of biomarker data in association with clinical trials to enhance data comparisons, reduce duplication, and facilitate data submission for regulatory approval.

  • In consult with industry and FDA, develop standard case report forms incorporating common data elements to improve information sharing among cancer researchers and to optimize data requirements.

Suggested Citation:"Appendix A: Previous and Ongoing Analyses Undertaken by NCI." Institute of Medicine. 2010. A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. Washington, DC: The National Academies Press. doi: 10.17226/12879.
×

Cooperation

  • NCI should appoint a group to develop legal templates for interactions between universities, Cooperative Groups, and industry for material transfer agreements, clinical cooperative agreements, and Cooperative Research and Development Agreements (CRADAs).

  • Develop commonly accepted clauses for clinical trial contracts with industry to reduce the lead time needed to open trials.

  • Realign NCI and academic incentives to promote collaborative team science.

Process improvement

  • Cooperative Groups and the Cancer Therapy Evaluation Program (CTEP) need well-defined timelines for protocol development, approval, and activation and need to have clearly stated positive and negative consequences of meeting or not meeting timelines.

  • All groups participating in an inter-Group trial should be able to conduct direct registration and submit forms directly to the coordinating Group.

  • Amendments and addenda to trials should become the full responsibility of the Group conducting the study and should not require the approval of NCI (although they should be filed with NCI) .

  • The interval for Cooperative Group renewal should be lengthened to 8 to 10 years for established Groups.

  • The separate protocol review processes of the Division of Cancer Treatment, Diagnosis and Centers (DCTDC) and the Division of Cancer Prevention and Control (DCPC) should be combined.

  • Cooperative Groups should be engaged as soon as possible in CTEP CRADA negotiations that require Group participation.

  • Reduce institutional barriers to timely trial initiation.

  • Expand awareness of NCI-FDA expedited approval process to speed trial initiation.

  • Investigate integration of Phase II trials into the overall prioritization process to further coordinate the national clinical trials system.

  • Develop a funding prioritization process that ensures that critical correlative science and quality-of-life studies can be conducted in a timely manner.

  • Build a credentialing system for investigators and sites recognized by NCI and industry to allow faster trial initiation and to keep the investigative community abreast of legal, safety, and regulatory changes.

  • Promote the adoption of an NCI central institutional review board-facilitated review process to reduce the time and resources needed to open trials at individual sites.

Suggested Citation:"Appendix A: Previous and Ongoing Analyses Undertaken by NCI." Institute of Medicine. 2010. A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. Washington, DC: The National Academies Press. doi: 10.17226/12879.
×

 

Armitage Report

Clinical Trials Working Group

Organizational and structural improvement

  • NCI should urge FDA to form a single oncology advisory committee with provision for obtaining the necessary expertise for ad hoc review.

  • Inter-Group trials should be harmonized and simplified.

  • The Decision Network needs to be publicized and would benefit from external input. CTEP must clarify its role in reviewing novel drugs with questionable patent status to better move agents toward clinical trials.

  • CTEP’s role should depend on the type of agent studied:

    • For Phase II and III studies not involving new agents, CTEP should approve study concepts and collaboratively establish research priorities; CTEP’s authority should otherwise be limited to regulatory and safety issues and prevention of unnecessary duplication.

    • For studies with investigational new agents, CTEP should retain its current legislated authority and responsibility, in partnership with industry and the Cooperative Groups.

  • For most prevention and control studies, the Groups should be provided with the authority to establish priorities and conduct studies. For large-scale cancer prevention and controlled Phase III studies, the DCPC or a combined DCTDC and DCPC review process should actively participate in concept approval and priority setting.

  • Treatment trials conducted through the Community Clinical Oncology Program (CCOP) mechanism should be transferred to DCTDC; cancer prevention studies conducted across the NCI clinical trials system should be the responsibility of the newly configured DCPC.

  • Create an Investigative Drug Steering Committee to work with the NCI to enhance design and prioritization of early-phase drug development trials.

  • Create a network of scientific steering committees leveraging inter-Group, Cooperative Group, Specialized Programs of Research Excellence (SPOREs), and cancer center structures to work with NCI in the design and prioritization of Phase III trials to better allocate resources, increase scientific quality, and reduce duplication.

  • Create a clinical trials oversight subcommittee of the National Cancer Advisory Board to advise the NCI director on the conduct of clinical trials across the Institute.

  • Develop a coordinated NCI organizational structure to manage the entire clinical trials enterprise supported by the NCI.

Accrual

  • High-quality patient-oriented public awareness campaigns presenting the value of clinical trials should be a priority.

  • Increase patient and public awareness and understanding of clinical trials.

Suggested Citation:"Appendix A: Previous and Ongoing Analyses Undertaken by NCI." Institute of Medicine. 2010. A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. Washington, DC: The National Academies Press. doi: 10.17226/12879.
×

 

  • The public should have access to all information about ongoing clinical trials.

  • NCI should continue to improve efforts to recruit and retain members of minority groups, medically underserved populations, and elderly individuals in clinical trials and to tailor recruitment and retention approaches to address linguistic and cultural differences.

  • Representatives of patient and high-risk communities need to be integrated into the clinical trials decision-making process.

  • NCI-designated cancer centers should be encouraged to participate in Cooperative Group research and participation should be reviewed favorably in the cancer center review process.

  • NCI should develop strategies to convince payors that clinical trials are the preferred way to manage patients.

  • The informed-consent process must be modified and simplified, and NCI should work with the Office for Protection from Research Risks (now the Office for Human Research Protection) to develop a template for informed-consent forms for distribution to clinical scientists and the patient community.

  • Increase minority patient access to clinical trials to improve the participation of underserved and underrepresented populations.

  • Increase community oncologist and patient advocate involvement in clinical trial design and prioritization, which will increase patient accrual and better address the practical and quality-of-life concerns in clinical trials.

Funding

  • NCI should work with other governmental agencies and private organizations, including third-party payors, to determine costs associated with Phase I to IV clinical trials and should develop a plan for funding the research required to determine these costs.

  • NCI should increase funding to Cooperative Groups to fully recommended levels.

  • NCI should provide extra funds to the coordinating Group of an intergroup trial to cover additional expenses.

  • Funding should be based on costs of performing as a headquarters office, proportional to CCOP membership.

  • Systems for awarding credit and funding to institutions participating in intergroup studies must be developed.

  • NCI should work with CMS to identify clinical studies that address the objectives of both the NCI and CMS for which CMS may provide reimbursement for routine costs in investigational trials.

  • Restructure Phase III funding model to promote rapid patient accrual rates and cost-effectiveness.

Suggested Citation:"Appendix A: Previous and Ongoing Analyses Undertaken by NCI." Institute of Medicine. 2010. A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. Washington, DC: The National Academies Press. doi: 10.17226/12879.
×

 

Armitage Report

Clinical Trials Working Group

Investigator recruitment

  • Awards to midcareer and senior scientists should emphasize salary to ensure protected time for clinical investigation.

  • Clinical investigator salary lines should be available on cancer center’s core grants and should be for a 3- to 5-year duration.

  • K12 and T32 awards should be expanded, and K08 awards should be directed to patient-oriented research.a NCI should create new awards and salary support for junior faculty.

  • NCI should fund at least 10 fellowship programs that provide a formalized academic degree program for clinical scientists.

  • Cooperative Group grants should include a salary commitment to responsible committee chairs to ensure that time and effort are matched by salary support in planning, implementation, and review of trials.

  • No recommendations on investigator recruitment.

aK12 awards support newly trained clinicians appointed by an institution for development of independent research skills and experience in a fundamental science within the framework of an interdisciplinary research and development program. T32 awards enable institutions to make National Research Service Awards to individuals selected by them for predoctoral and postdoctoral research training in specified shortage areas. K08 awards provide the opportunity for promising medical scientists with demonstrated aptitude to develop into independent investigators, or for faculty members to pursue research aspects of categorical areas applicable to the awarding unit, and aid in filling the academic faculty gap in these shortage areas.

SOURCES: NCI, 1997, 2005b.

Suggested Citation:"Appendix A: Previous and Ongoing Analyses Undertaken by NCI." Institute of Medicine. 2010. A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. Washington, DC: The National Academies Press. doi: 10.17226/12879.
×

investigator recruitment. Interestingly, the Armitage report gave several recommendations on the retention and recruitment of clinical scientists, whereas the CTWG report’s 22 recommendations did not address recruitment and retention issues. Despite the time lapse between the release of the two reports, several themes emerged from both reports, including the importance of data standardization, the need for a comprehensive database of NCI trials, improved public awareness of clinical trials, and the need to reduce the time it takes to initiate a clinical trial.

RESPONSE TO THE CTWG REPORT

NCI has launched several initiatives in response to the CTWG report, as delineated in Box A-2. In addition, NCI has launched an evaluation plan in response to the CTWG recommendation for a quantitative and qualitative, evidence-based evaluation to assess measures of the program management process, the system performance process, and system outcomes.1 The evaluation plan consists of a baseline feasibility analysis, an interim evaluation of specific initiatives related to these measures, and final evaluations at specified intervals after implementation of the initiatives. A goal is to develop a structured framework for continuous monitoring and feedback to accommodate midcourse corrections.

The evaluation aims to compare the baseline to the future on the basis of system outcome measures (overall output) and system performance measures (performance of individual CTWG initiatives). The system outcome measures are intended to gauge the quality and impact of clinical trials and the efficiency of both trial development and initiation and trial conduct. NCI has engaged evaluation specialists to assist with development of the definitions, survey instruments, statistical adjustments, and other tools; to conduct the evaluations; and to determine the appropriate timing for examining the various measures in the context of the implementation timelines and the nature of the impacts envisioned.

The baseline evaluation of the current system was completed in 2008 to provide a basis for ascertaining the value of the restructuring effort. The results of that baseline evaluation are being analyzed by a Working Group of the Clinical Trials and Translational Research Advisory Committee (formerly the Clinical Trials Advisory Committee [CTAC]), which will propose which elements of the recommended evaluation system should be implemented and establish a timeline for follow-up evaluations.

Suggested Citation:"Appendix A: Previous and Ongoing Analyses Undertaken by NCI." Institute of Medicine. 2010. A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. Washington, DC: The National Academies Press. doi: 10.17226/12879.
×

BOX A-2

NCI Initiatives in Response to the CTWG Report

NCI has launched initiatives in six categories in response to the CTWG report. The objectives and current status of those initiatives are briefly described below. Many of these activities are also described in Chapter 3.


Enterprise-wide initiatives aim to enhance coordinated leadership of the clinical trials enterprise by addressing ongoing National Cancer Advisory Board oversight of clinical trials and an integrated NCI organizational structure for clinical trials management. NCI established the Clinical Trials Advisory Committee (CTAC; since renamed the Clinical Trials and Translational Research Advisory Committee) so that a broad range of stakeholders could provide advice on NCI-supported national clinical trials (both extramural and intramural) to the NCI director, deputy directors, and division directors. NCI also established the Clinical Trials and Translational Research Operations Committee (CTROC) as an internal NCI advisory committee responsible for review of ongoing clinical trials and prioritization of proposed NCI-supported clinical trials, correlative science programs, and translational research. CTROC members include the directors of all NCI divisions, offices, and centers that have clinical trials or translational science portfolios. The Coordinating Center for Clinical Trials was established to oversee implementation of the 22 initiatives recommended by the CTWG in 2005, as well as 15 initiatives recommended by the TRWG in 2007. The center, which resides within the NCI’s Office of the Director, facilitates and manages the operations of CTAC and CTROC in conjunction with all NCI divisions, offices, and centers.


Coordination initiatives aim to improve coordination and cooperation among the functionally diverse components of the current system, including industry and federal regulatory agencies. Currently, NCI is working to establish a comprehensive database containing regularly updated information on all NCI-funded interventional clinical trials. Grantees will be requested to enter specific information about each clinical trial into the database.


Prioritization and scientific initiatives aim to improve prioritization and scientific quality by developing a more open and transparent process for the design and prioritization of clinical trials that are science driven and that meet the needs of patient care. NCI has established an Investigational Drug Steering Committee and several disease-specific steering committees, as described in Chapter 3.


Standardization initiatives aim to improve standardization of the tools and procedures used for trial design, data capture, data sharing, and administrative functions to minimize duplication of effort and to facilitate the development of a shared infrastructure to support an integrated national cancer clinical trials network. Working with the CEO Roundtable on Cancer, NCI developed the Standard Terms of Agreement for Research Trials clauses to help cut the time spent on contract negotiations between pharmaceutical or biotechnology companies and academic medical centers.

Suggested Citation:"Appendix A: Previous and Ongoing Analyses Undertaken by NCI." Institute of Medicine. 2010. A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. Washington, DC: The National Academies Press. doi: 10.17226/12879.
×

Operational efficiency initiatives aim to improve operational efficiency by increasing the rate of patient accrual and reducing operational barriers so that trials can be initiated and executed in a timely, cost-effective manner. NCI funded a study to identify institutional barriers to the initiation of clinical trials by documenting and analyzing the steps needed to activate clinical trials (Dilts and Sandler, 2006; Dilts et al., 2006, 2008). In addition, since 2006, selected grantees have received administrative supplements to increase funding for the recruitment of minority and medically underserved patients to NCI clinical trials. In 2008, nine continuation supplements totaling $830,000 and four new supplements totaling $399,000 were awarded.


Informatics initiatives aim to define, design, build, and deliver a comprehensive clinical trials informatics infrastructure that will serve all of the critical stakeholders. NCI plans to rely on the NCI Center for Bioinformatics to provide program management and infrastructure through caBIG to achieve these aims.


SOURCE: See http://restructuringtrials.cancer.gov/initiatives/overview.

Results of the Baseline Feasibility Study

The baseline measures of system performance for the CTWG initiatives included incentives for collaboration among investigators, the extent of multisite Phase II and multi-Cooperative Group Phase III trials, the extent of collaboration between industry and NCI, the nature and quality of clinical trial prioritization processes, and the distribution and cost-effectiveness of accrual across sites (Doroshow, 2008). The baseline measures did not consider initiatives in which there was little or no activity ongoing prior to the CTWG report, such as a comprehensive clinical trials database, the level of caBIG (cancer Biomedical Informatics Grid)-compatible clinical information technology, the value added by the Investigational Disease Steering Committee and Scientific Steering Committee processes, the impact of correlative science funding and standardization, the value and use of standardized clinical trial tools, and the cost savings achieved by shifting patient accrual to highly accruing, more efficient sites.

Multiple sources of data were used for the baseline feasibility analysis, including interviews, database analyses, and reviews of factual information in documents. Baseline interviews were held in 2007 with 81 stakeholders (investigators conducting Phase I, II, and III trials; principal investigators of the Community Clinical Oncology Program, investigators conducting

Suggested Citation:"Appendix A: Previous and Ongoing Analyses Undertaken by NCI." Institute of Medicine. 2010. A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. Washington, DC: The National Academies Press. doi: 10.17226/12879.
×

industry trials, and NCI staff). The questions were mostly open-ended, and some questions were designed to elicit perceptions of specific facts or events. Two CTEP databases (the Clinical Data Update System and the Division of Cancer Prevention Enterprise System Knowledgebase) have been analyzed, and the analysis includes all clinical trials, letters of intent (LOIs) for the conduct of clinical trials, and clinical trial concepts that were active between January 1, 2000, and December 31, 2005. However, no current database captures all clinical trials performed at the cancer centers.

The baseline document review covers NCI program guidelines, cancer treatment guidelines, and academic medical center tenure and promotion guidelines. An expert panel, composed of nine individuals who conduct NCI-funded clinical trials, an individual from industry who conducts clinical trials, and a patient advocate, participated in the development of measures and interview guides and reviewed the key findings at the end. Plans for future evaluations include the refinement of baseline measures and the development of new measures; incorporation of additional information into clinical trials databases to strengthen future evaluation efforts; and the development of an initiative-specific timeline.

For the system outcome measures, the analysis of the quality of trials focused on early closure and publications. Recommendations were made to include fields in clinical trials databases to indicate early closure and the reason for closure, as well as to report the publications that resulted from the clinical trial. Suggestions were also made to include Phase II and III linkages in clinical trials databases, as well as measures to evaluate the strength of evidence for dose and toxicity criteria in Phase I trials and outcome in Phase II and III trials. In addition, the group recommended that the databases include earlier time points in concept development, as well as fields for trial complexity and patient eligibility criteria to facilitate the interpretation of the accrual data.

To assess the impact of the changes on fostering collaboration, the group suggested that future interviews examine collaboration in trial design and that NCI develop a way to track collaborative trial efforts in the clinical trials databases. Collaboration in accrual and accrual through the Cancer Trials Support Unit (CTSU) also was considered, and repeat analyses at regular intervals were suggested (Doroshow, 2008).

Operational Efficiency Working Group

As discussed in Box A-2, the CTWG report called for an analysis of the institutional barriers that prolong the time from concept approval to accrual of the first patient onto a trial. In response, CTAC established the OEWG to recommend strategies and implementation plans based on the findings of its analysis. Sixty-three clinical trial stakeholders participated in the OEWG, including 10 Cooperative Group chairs, 8 cancer center

Suggested Citation:"Appendix A: Previous and Ongoing Analyses Undertaken by NCI." Institute of Medicine. 2010. A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. Washington, DC: The National Academies Press. doi: 10.17226/12879.
×

directors, clinical investigators, statisticians, protocol and trial specialists, a community oncologist, NCI clinical trials leadership and staff, representatives of the pharmaceutical and biotechnology industries, patient advocates, representatives of the FDA, CMS, and the CTSU.

OEWG deliberations focused on identification of the key barriers to the timely activation of clinical trials and a commitment to achieve new target timelines for the steps in trial activation. In these discussions, the OEWG developed new process maps for trial activation and established firm dates to terminate the development of a trial protocol if all issues were not resolved. To achieve the targeted timelines, the OEWG developed recommendations and associated implementation plans (Box A-3). The OEWG target timeline for Phase III Cooperative Group trials is 300 days to complete steps under CTEP and Cooperative Group control (including concept review, protocol development, protocol review, and forms development). The 300-day timeline excludes contract and drug supply negotiations with industry partners as well as institutional review board (IRB) approval; however, if the protocol is not activated in 2 years, it will be terminated. For cancer center investigator-initiated trials, the target timeline is 90 days to complete protocol review and revision, forms development, IRB review, and ancillary committee review, and 180 days to complete all steps from protocol submission to trial activation. The Investigational Drug Branch (IDB) early drug development Phase II target timeline is 210 days to complete steps under CTEP/IDB and extramural control, including letter of intent review, protocol development, protocol review, and forms development. This timeline excludes industry negotiations, arranging drug supply, and IRB and FDA approval; however, if the protocol is not activated within 18 months, it will be terminated.

TRANSLATIONAL RESEARCH WORKING GROUP REPORT

The TRWG was established in June 2005 under the auspices of the National Cancer Advisory Board and was charged with evaluating the current status of the NCI’s investment in translational research, envisioning its future, and developing recommendations and implementation plans to realize that vision. The work of the TRWG was intended to complement and extend the work of the CTWG. While the CTWG report primarily focused on late translation (Phase III trials), the TRWG’s focus was on early translation activities, including partnerships and collaborations among government, academia, and industry; intervention development; and early-stage trials.2

2

The TRWG used the definitions of early- and late-stage translation of the President’s Cancer Panel (NCI, 2005a).

Suggested Citation:"Appendix A: Previous and Ongoing Analyses Undertaken by NCI." Institute of Medicine. 2010. A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. Washington, DC: The National Academies Press. doi: 10.17226/12879.
×

BOX A-3

Operational Efficiency Working Group Recommendations

Cooperative Group Process Improvement

  • Recommendation 1: Group-specific action plan to achieve OEWG target timeline

    • Potential staffing changes

      • Physician senior protocol officers

      • Nonphysician trial development managers

      • Specialist medical writers

    • Performance of trial development steps in parallel

    • Direct, coordinated interactions to resolve issues

    • Project management and protocol tracking tools

  • Recommendation 2: CTEP action plan to achieve OEWG target timeline

    • Project managers

      • Manage overall protocol review, revision, and approval process

      • Facilitate interactions between CTEP and the Cooperative Groups

    • Coordinated NCI scientific review to identify all issues at time of initial concept review

    • Prompt communication of critical issues in advance of formal written reviews

    • Streamlined methods for communicating comments

    • Differentiation of advisory comments from those requiring a response

    • Project management and protocol tracking tool

  • Recommendation 3: Collaborative Group-CTEP process for concept and protocol revision

    • Direct, coordinated interactions to resolve issues

    • High priority for devotion of time to issue resolution

    • Resolution of fundamental aspects of study design at concept stage

    • Focus of interactions at protocol stage on mechanics of completion of protocol embodying an agreed-upon concept

      • Prompt communication and resolution of major differences

      • Minimization of time discussing noncritical differences of opinion

      • Minimization of time and effort for routine or pro forma revisions

    • Rapid arbitration for any issues not resolved quickly

  • Recommendation 4: Development of approaches to reward performance against timelines

    • Establish a comprehensive, reliable system for reporting timeline performance for each step in trial activation process

    • Collect timeline performance data for at least 1 year and assess accuracy and value of the data and reports

    • Analyze performance data by individual Cooperative Groups and across the Group system in comparison with target timelines

    • Joint Cooperative Group-NCI deliberations concerning

      • Linking incentives to Group-specific timeline performance

      • Incorporating performance against timeline targets

    • CTEP inclusion of timeline performance in its annual staff performance evaluations

Suggested Citation:"Appendix A: Previous and Ongoing Analyses Undertaken by NCI." Institute of Medicine. 2010. A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. Washington, DC: The National Academies Press. doi: 10.17226/12879.
×

Early Drug Development Phase II Trial Activation Process Improvement

  • Recommendation 5: CTEP action plan to achieve OEWG target timeline

    • Project managers

      • Management of overall protocol review, revision, and approval process

      • Facilitation of interactions among CTEP, principal investigators, and industry

    • Teleconferences to resolve issues for LOIs on hold

    • Prompt communication of disapprovals in advance of review letter

    • Streamlined methods for communicating comments

    • Differentiation of advisory comments from those requiring response

    • Project management and protocol tracking tools

  • Recommendation 6: Collaborative Group, N01 research and development contracts, CTEP process for LOI and protocol revision

    • Direct, coordinated interactions to resolve issues (within 14 days of LOI review)

    • High priority on devoting time to issue resolution

    • Resolution of fundamental aspects of study design at LOI stage

    • Focus of interactions at protocol stage on mechanics of completing a protocol embodying an agreed-upon LOI

      • Prompt communication and resolution of major differences

      • Minimization of time spent discussing noncritical differences of opinion

      • Minimization of time and effort for routine or pro forma revisions

    • Rapid arbitration for any issues not resolved quickly

Cancer Center Process Improvement

  • Recommendation 7: Cancer center-specific action plan to achieve OEWG target timeline

    • Potential action plan elements

      • Specialist medical writers

      • Direct, coordinated interactions to resolve differences

      • Project management and protocol tracking tool

    • Center-specific timeline targets

      • Modification of OEWG target to reflect specific cancer center environment

      • Analysis of targets for reasonableness by cancer center directors and NCI

      • Reporting of timeline data against target on an annual basis

      • Annual report on actions taken against centers performing below expectations

    • Funding sources

      • Allowance for explicit use of Cancer Center Support Grant (CCSG) funds for protocol development

      • Provision of supplemental funds to implement action plan

  • Recommendation 8: Streamline university contracting and financial review processes

    • System-level activities

Suggested Citation:"Appendix A: Previous and Ongoing Analyses Undertaken by NCI." Institute of Medicine. 2010. A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. Washington, DC: The National Academies Press. doi: 10.17226/12879.
×
  • Education of universities on NCI Standardized Clauses for Clinical Trial Agreements

  • Development of standardized clauses for other types of agreements

  • Collaboration with Clinical and Translational Science Awards program to streamline processes

  • Institution-level activities

    • Education of stakeholders on NCI Standardized Clauses for Clinical Trial Agreements

    • Establishment of master agreements with individual companies

    • Consideration of use of nonfederal funds for university legal and contracting staff devoted to cancer center trials

    • Direct interactions among cancer center, university, and hospital staff to resolve issues

Standardization of Tools and Templates

  • Recommendation 9: Form a working group involving the NCI, Cooperative Group, and cancer center staff to coordinate standardization efforts

    • Compilation of inventory of protocol templates, data elements, case report form modules, etc., from Cooperative Groups, cancer centers, and the NCI

    • Analysis of inventory to identify current standards, best-in-class products, redundant development efforts, and unmet needs

    • Analysis of status and output of existing standardization efforts

    • Identification of tools and templates for which standardization is mandatory versus recommended or optional

    • Identification of standards needed for interoperability

    • Development of a coordinated process for implementing standards

Recommendations

In developing its recommendations, the TRWG outlined the current challenges confronting early translational research at the NCI (Box A-4). To address these challenges, the TRWG developed 15 recommendations in three categories: coordinated management, tailored funding programs, and operational effectiveness (Table A-2). In addition, the TRWG constructed six developmental pathways to describe the decision-making points and processes along which translational research occurs for six domains: bio-specimen-based risk assessment devices, image-based risk assessment agents

Suggested Citation:"Appendix A: Previous and Ongoing Analyses Undertaken by NCI." Institute of Medicine. 2010. A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. Washington, DC: The National Academies Press. doi: 10.17226/12879.
×

Enhanced Biomarker Funding and Capabilities

  • Recommendation 10: Enhancement of funding and capabilities for use of biomarkers in NCI-funded clinical trials

    • Expansion of the Biomarker, Imaging, and Quality of Life Studies Funding Program to large randomized Phase II trials

    • Support biomarker studies for early-phase trials

    • Requirement for clinical trial concepts and LOIs to describe proposed integral or integrated biomarker studies

    • Provision of funding for development, validation, and conduct of clinical-grade assays

    • Development of standards for qualifying sites to conduct imaging studies associated with clinical trials

Cancer Center Trial Prioritization

  • Recommendation 11: Performance of rigorous review of clinical trial concepts in advance of protocol development

    • Specification of concept review process in CCSG guidelines

      • Approval or disapproval by disease group or throughout the cancer center

      • Uniformity of reviews across diseases

      • Content of a concept document

      • Criteria by which concepts are reviewed

    • NCI should mandate the specific process or criteria

    • Applicable to all trials: investigator-initiated, Cooperative Group, and N01 trials

SOURCE: Doroshow and Hortobagyi, 2010.

and techniques, anticancer agents (drugs or biologics), immune response modifiers, interventive devices, and lifestyle alterations (Cheever et al., 2008; Dorfman et al., 2008a,b; Hawk et al., 2008a,b; Schilsky et al., 2008; Srivastava et al., 2008).

Some TRWG recommendations are outgrowths of the CTWG initiatives, such as the Clinical and Translational Advisory Committee (CTAC; previously the Clinical Trials Advisory Committee, created in response to the CTWG recommendations). The TRWG report expanded the scope of the CTAC committee to include translational research, noting that CTAC

Suggested Citation:"Appendix A: Previous and Ongoing Analyses Undertaken by NCI." Institute of Medicine. 2010. A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. Washington, DC: The National Academies Press. doi: 10.17226/12879.
×

BOX A-4

Translational Research Working Group Assessment of Current Challenges in Translational Research

  • Insufficient coordination and integration results in a fragmented translational research effort that risks duplication and missed opportunities.

  • The absence of clearly designated funding and adequate incentives for researchers threatens the perceived importance of translational research within the NCI enterprise.

  • The absence of structured, consistent review and prioritization processes tailored to the characteristics and goals of translational research makes it difficult to direct resources to critical needs and opportunities.

  • The multidisciplinary nature of translational research and the need to integrate sequential steps in complex developmental pathways warrant dedicated project management resources.

  • Translational research core services can be duplicative and inconsistently standardized, with capacity being poorly matched to the need.

  • Collaboration with industry delays appropriate developmental handoffs.

  • Extended negotiation on intellectual property issues delays or prevents potentially productive collaborations.

  • Insufficient collaboration and communication between basic and clinical scientists and the paucity of effective training opportunities limit the supply of experienced translational researchers.

SOURCE: NCI, 2007.

was already responsible for early-stage trials and correlative science studies. The TRWG report also indicated that integrated oversight would facilitate the coordination and prioritization process for both early- and late-stage translational research. Other report recommendations focused on prioritizing translational research activities at NCI, providing better project management of translational research activities, establishing enhanced bio-specimen repositories and analytical methods, and ensuring the provision of training and career incentives for early translational research.

Suggested Citation:"Appendix A: Previous and Ongoing Analyses Undertaken by NCI." Institute of Medicine. 2010. A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. Washington, DC: The National Academies Press. doi: 10.17226/12879.
×

TABLE A-2 Summary of TRWG Recommendations and Implementation Status

Category

Specific Recommendations

Implementation Status

Coordinated management

• Establish a flexible, integrated organizational approach that coordinates early translational research across NCI.

• Expansion of CTAC to include translational research expertise; expansion of the Clinical Trials Operations Committee (and name change to Clinical Trials and Translational Research Operations Committee) to include translational research responsibilities; expansion of Coordinating Center for Clinical Trials to include Translational Research Support Team

• Designate a specific portion of the NCI budget for early translational research.

 

• Develop a set of award codes that accurately capture the nature and scope of the early translational research portfolio.

• Pilot project with NCI’s Division of Extramural Activities to code grants for translational research on the basis of the TRWG pathways; comparison with principal investigator’s assessment of projects to look for consistency and interpretation of pathways

• Establish a distinctive prioritization process for early translational research.

• Two-day NCI translational science meeting (NCI Translates) held in November 2008 and 2009 to explore potential of translational research prioritization and acceleration, as recommended by the TRWG report

 

• Pilot project to prioritize cancer antigens within the immune response modifier pathway; project expanded to prioritize translational research opportunities within the immune response modifier pathway

Suggested Citation:"Appendix A: Previous and Ongoing Analyses Undertaken by NCI." Institute of Medicine. 2010. A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. Washington, DC: The National Academies Press. doi: 10.17226/12879.
×

Category

Specific Recommendations

Implementation Status

Tailored funding programs

• Modify multiproject collaborative award guidelines, as appropriate, to facilitate early translational research.

• CTAC Coordination Subcommittee Guideline Harmonization Working Group mission: promote collaborative team science and ensure that guidelines for different clinical trials funding mechanisms are aligned, eliminate redundancy and duplication while proactively encouraging collaboration, harmonize program guidelines and develop incentives to foster collaboration among all components of the clinical trials infrastructure, including cancer centers, Specialized Programs of Research Excellence, and Cooperative Groups

• Improve processes and mechanisms for funding investigator-initiated early translational research.

 

• Establish a special translational research acceleration project (STRAP) to advance prioritized early translational research opportunities.

• Pilot project to establish a STRAP for the immune response modifier pathway

• Establish a funding program for early translational research that requires academia and industry collaboration involving resource sharing or cofunding.

 

• Integrate access to manufacturing and other preclinical development services according to good manufacturing practices and good laboratory practices more effectively with milestone-driven early translational research projects.

• Development of the NCI Experimental Therapeutics Program, a new drug discovery and development pipeline that can partner with researchers to bring new cancer treatments to patients

Suggested Citation:"Appendix A: Previous and Ongoing Analyses Undertaken by NCI." Institute of Medicine. 2010. A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. Washington, DC: The National Academies Press. doi: 10.17226/12879.
×

Operational effectiveness

• Establish a formal project management system for early translational research.

• New Project Management Office established within the NCI Division of Cancer Treatment and Diagnosis

• Establish a system to coordinate core services essential for early translational research.

• CTAC Coordination Subcommittee is developing criteria for regional cores and guidelines to encourage sharing and reduce redundancy

• Enhance quality and accessibility of annotated biospecimen repositories and associated analytical methods.

• Enhancement of NCI’s Office of Biorepositories and Biospecimen Research

• Develop enhanced approaches for negotiation of intellectual property agreements and agent access.

• NCI and the Life Sciences Consortium of the CEO Roundtable on Cancer have jointly developed a set of common clauses, the Standard Terms of Agreement for Research Trial clauses, that are accessible for use by any party initiating a trial. These standard clauses provide common language for use as a starting point in the contract agreements that govern clinical trials.

• Enhance interactions and collaborations with foundations and advocacy groups to advance early translational research.

 

• Enhance training and career incentives for early translational research.

 

SOURCES: Cheever et al., 2009; Clinical Trials Advisory Committee, 2008; Hawk et al., 2008b; NCI, 2007.

Suggested Citation:"Appendix A: Previous and Ongoing Analyses Undertaken by NCI." Institute of Medicine. 2010. A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. Washington, DC: The National Academies Press. doi: 10.17226/12879.
×

REFERENCES

Cheever, M. A., J. Schlom, L. M. Weiner, K. H. Lyerly, M. L. Disis, A. Greenwood, O. Grad, and W. G. Nelson. 2008. Translational Research Working Group developmental pathway for immune response modifiers. Clinical Cancer Research 14(18):5692–5699.

Cheever, M. A., J. P. Allison, A. S. Ferris, O. J. Finn, B. M. Hastings, T. T. Hecht, I. Mellman, S. A. Prindiville, J. L. Viner, L. M. Weiner, and L. M. Matrisian. 2009. The prioritization of cancer antigens: A National Cancer Institute pilot project for the acceleration of translational research. Clinical Cancer Research 15(17):5323–5337.

Clinical Trials Advisory Committee. 2008. CTAC minutes, June 25. http://deainfo.nci.nih.gov/advisory/ctac/0608/25jun08mins.pdf.

Dilts, D. M., and A. B. Sandler. 2006. Invisible barriers to clinical trials: The impact of structural, infrastructural, and procedural barriers to opening oncology clinical trials. Journal of Clinical Oncology 24(28):4545–4552.

Dilts, D. M., A. B. Sandler, M. Baker, S. K. Cheung, S. L. George, K. S. Karas, S. McGuire, G. S. Menon, J. Reusch, D. Sawyer, M. Scoggins, A. Wu, K. Zhou, and R. L. Schilsky. 2006. Processes to activate Phase III clinical trials in a cooperative oncology group: The case of Cancer and Leukemia Group B. Journal of Clinical Oncology 24(28):4553–4557.

Dilts, D. M., A. B. Sandler, S. Cheng, J. Crites, L. Ferranti, A. Wu, R. Gray, J. MacDonald, D. Marinucci, and R. Comis. 2008. Development of clinical trials in a cooperative group setting: The Eastern Cooperative Oncology Group. Clinical Cancer Research 14:3427–3433.

Dorfman, G. S., T. S. Lawrence, and L. M. Matrisian. 2008a. The Translational Research Working Group developmental pathway for interventive devices. Clinical Cancer Research 14(18):5700–5706.

Dorfman, G. S., D. C. Sullivan, M. D. Schnall, and L. M. Matrisian. 2008b. The Translational Research Working Group developmental pathway for image-based assessment modalities. Clinical Cancer Research 14(18):5678–5684.

Doroshow, J. 2008. CTWG Evaluation Plan: Results of Baseline Feasibility Analysis. Presented at the National Cancer Advisory Board Meeting, February 2008, Bethesda, MD.

Doroshow, J. H., and G. Hortobagyi. 2010. Compressing the Timeline for Cancer Clinical Trial Activation. Operational Efficiency Working Group Final Report. Presented to the Clinical and Translational Research Advisory Committee, March 2010, Bethesda, MD.

Hawk, E. T., A. Greenwood, E. R. Gritz, A. McTiernan, T. Sellers, S. D. Hursting, S. Leischow, and O. Grad. 2008a. The Translational Research Working Group developmental pathway for lifestyle alterations. Clinical Cancer Research 14(18):5707–5714.

Hawk, E. T., L. M. Matrisian, W. G. Nelson, G. S. Dorfman, L. Stevens, J. Kwok, J. Viner, J. Hautala, and O. Grad. 2008b. The Translation Research Working Group developmental pathways: Introduction and overview. Clinical Cancer Research 14(18):5664–5671.

NCI (National Cancer Institute). 1997. Report of the National Cancer Institute Clinical Trials Program Review Group. http://deainfo.nci.nih.gov/ADVISORY/bsa/bsa_program/bsact-prgmin.htm#8a (accessed November 19, 2008).

NCI. 2005a. President’s Cancer Panel 2004–2005 Annual Report: Translating research into cancer care: Delivering on the promise. Bethesda, MD: National Cancer Institute.

NCI. 2005b. Restructuring the National Cancer Clinical Trials Enterprise. Report of the Clinical Trials Working Group of the National Cancer Advisory Board. Bethesda, MD: National Cancer Institute.

NCI. 2007. Transforming Translation—Harnessing Discovery for Patient And Public Benefit. Report of the Translational Research Working Group of the National Cancer Advisory Board. Bethesda, MD: National Cancer Institute.

Suggested Citation:"Appendix A: Previous and Ongoing Analyses Undertaken by NCI." Institute of Medicine. 2010. A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. Washington, DC: The National Academies Press. doi: 10.17226/12879.
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Schilsky, R. L., G. Gordon, T. M. Gilmer, S. A. Courtneidge, L. M. Matrisian, O. Grad, and W. G. Nelson. 2008. The Translational Research Working Group developmental pathway for anticancer agents (drugs or biologics). Clinical Cancer Research 14(18):5685–5691.

Srivastava, S., J. W. Gray, B. J. Reid, O. Grad, A. Greenwood, and E. T. Hawk. 2008. Translational Research Working Group developmental pathway for biospecimen-based assessment modalities. Clinical Cancer Research 14(18):5672–5677.

Suggested Citation:"Appendix A: Previous and Ongoing Analyses Undertaken by NCI." Institute of Medicine. 2010. A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. Washington, DC: The National Academies Press. doi: 10.17226/12879.
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The National Cancer Institute's (NCI) Clinical Trials Cooperative Group Program has played a key role in developing new and improved cancer therapies. However, the program is falling short of its potential, and the IOM recommends changes that aim to transform the Cooperative Group Program into a dynamic system that efficiently responds to emerging scientific knowledge; involves broad cooperation of stakeholders; and leverages evolving technologies to provide high-quality, practice-changing research.

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